Cervical Cancer
Cervical cancer is a malignant neoplasm arising from the cervical epithelium, most commonly the squamocolumnar junction, predominantly caused by persistent high-risk human papillomavirus (HPV) infection.
Cervical Cancer
Cervical cancer is a malignant neoplasm arising from the uterine cervix, most commonly at the squamocolumnar junction (SCJ) — the transformation zone where the columnar epithelium of the endocervix meets the squamous epithelium of the ectocervix. This is the area of most active metaplasia and therefore highest vulnerability to oncogenic insults.
- "Cervical" → from Latin cervix = "neck" (the cervix is the "neck" of the uterus)
- The vast majority (> 99%) of cervical cancers are causally linked to persistent infection with high-risk Human Papillomavirus (HPV)
Core Concept — HPV is Necessary but Not Sufficient
Most cervical cancer is due to HPV, but the presence of HPV does not mean you will develop cervical cancer. HPV is NECESSARY, but NOT SUFFICIENT. [1][2] This is a critical distinction: HPV infection is extremely common in sexually active individuals, but the vast majority clear it. It is persistent infection with high-risk strains, combined with cofactors, that drives malignant transformation.
2. Epidemiology
- 4th most common cancer in women worldwide (~660,000 new cases and ~350,000 deaths annually, GLOBOCAN 2022 estimates)
- Disproportionately affects low- and middle-income countries (LMICs), where screening and vaccination coverage are poor — ~90% of deaths occur in LMICs
- Incidence and mortality have been declining in countries with organised screening (e.g., Pap smear, HPV testing) and HPV vaccination programmes
- Cervical cancer is the 8th most common cancer in women in Hong Kong (Hong Kong Cancer Registry data)
- Approximately 500+ new cases per year; ~150–170 deaths per year
- Median age of presentation: 55 [3]
- Hong Kong introduced a government-funded HPV vaccination programme for girls in 2019/2020 (targeting girls before sexual debut)
- The Cervical Screening Programme (CSP) has been running since 2004, recommending screening for women aged 25–64 who have ever been sexually active
- Despite these efforts, uptake of screening remains suboptimal, particularly among older, lower socio-economic groups and new immigrants
- Bimodal peak: one peak at 35–39 years, another at 60–64 years
- Pre-invasive disease (CIN) detected earlier (25–35 years), reflecting the long latent period from HPV infection → CIN → invasive cancer (typically 10–20 years)
3. Anatomy and Function of the Cervix
Understanding cervical anatomy is essential because the cancer arises at a very specific anatomical zone.
- The cervix is the inferior, narrow portion of the uterus, projecting into the upper vagina
- It is approximately 2.5–3 cm long and divided into:
- Ectocervix (portio vaginalis): the part visible on speculum exam, covered by stratified squamous epithelium (same as vagina) — tough, multi-layered, designed to withstand mechanical trauma
- Endocervical canal: the passage from the external os to the internal os, lined by simple columnar (glandular) epithelium — single-layered, mucus-secreting
- External os: the opening of the cervix into the vagina
- Internal os: the opening of the cervix into the uterine cavity
This is the most important anatomical concept in cervical cancer.
- The squamocolumnar junction (SCJ) is where the squamous epithelium of the ectocervix meets the columnar epithelium of the endocervix
- The position of the SCJ is dynamic — it changes with age, hormonal status, and parity:
- At puberty / during pregnancy / with OCP use: oestrogen causes the endocervical columnar epithelium to evert (ectropion), exposing it on the ectocervix. This exposed columnar epithelium then undergoes squamous metaplasia (replacement by squamous epithelium) — a physiological, protective response
- Post-menopausal: the SCJ recedes into the endocervical canal
- The transformation zone (TZ) is the area between the original SCJ and the new (current) SCJ — this is the zone of active squamous metaplasia
- Why does cancer arise here? Because actively dividing, metaplastic cells are highly susceptible to HPV infection and oncogenic transformation. HPV infects the basal cells of the epithelium, which are most accessible in the TZ where the epithelium is thin and actively remodelling
- Cervical branch of the uterine artery (from internal iliac artery)
- Venous drainage to the uterine venous plexus → internal iliac veins
- This is critical for staging and prognosis:
- Primary drainage: parametrial → obturator → internal iliac → external iliac nodes
- Secondary: common iliac → para-aortic nodes
- The pattern of lymph node involvement determines FIGO staging
- Sensory innervation from the inferior hypogastric plexus (S2–S4)
- The cervix has relatively few pain fibres (which is why early cervical cancer is often painless and biopsies of the ectocervix can be done without anaesthesia)
- Passage for menstrual blood, sperm, and the fetus during delivery
- Production of cervical mucus (by endocervical glands) — forms a barrier to infection and modulates sperm transport
- Structural support for the uterus (maintained by the cardinal and uterosacral ligaments — involvement of these is key in parametrial invasion/staging)
4. Risk Factors
| Risk Factor | Mechanism |
|---|---|
| Human Papillomavirus (HPV) infection | The necessary cause — virtually all cervical cancers are HPV-driven. High-risk types (HPV 16, 18, 31, 33, 45, 52, 58) are oncogenic |
| Early onset of sexual activity | Adolescent cervix has a large, exposed transformation zone with active metaplasia — these immature metaplastic cells are highly susceptible to HPV infection |
| Multiple sexual partners | Greater cumulative exposure to HPV; male partner's sexual history is also relevant |
| Oral contraceptive (OC) pill use | Long-term OCP use (> 5 years) is an independent cofactor: (1) may promote cervical ectropion, exposing more columnar epithelium to HPV; (2) hormonal effects may enhance HPV gene expression; (3) may also reflect less barrier contraception use |
| High-risk male partner | A male partner with many previous sexual partners carries higher HPV load |
| Risk Factor | Mechanism |
|---|---|
| Immunosuppression | HIV/AIDS, post-transplant immunosuppression, chronic steroid use → impaired cell-mediated immunity → failure to clear HPV → persistent infection → higher risk and faster progression to cancer |
| Smoking | Tobacco carcinogens (nicotine, cotinine) concentrate in cervical mucus → direct mutagenic effect on cervical epithelium; also impairs local immune response (reduces Langerhans cells in cervical epithelium) |
| Lower socio-economic class | Reduced access to screening, vaccination, healthcare; possibly higher rates of smoking, poor nutrition, and co-infections |
- Non-use of barrier contraception (condoms reduce but do not eliminate HPV transmission — HPV can infect skin not covered by condoms)
- High parity (≥ 5 full-term pregnancies) — possibly due to repeated cervical trauma and hormonal changes during pregnancy maintaining the ectropion
- Co-infection with other STIs (e.g., Chlamydia trachomatis, HSV-2) — may cause chronic cervical inflammation, facilitating HPV persistence
- Nutritional deficiencies (folate, vitamin C) — may impair epithelial integrity and immune function
Exam Framework for Risk Factors
5. Etiology and Pathophysiology
HPV is very common — basically if you have ever been sexually active, you have likely been exposed. [1][2]
- Human Papillomavirus (HPV) is a small, non-enveloped, double-stranded DNA virus of the Papillomaviridae family
-
200 HPV genotypes exist; ~40 infect the anogenital tract
- Classified by oncogenic potential:
- High-risk (oncogenic): HPV 16, 18, 31, 33, 45, 52, 58 (HPV 16 and 18 account for ~70% of all cervical cancers globally; in HK, HPV 52 and 58 are also particularly prevalent)
- Low-risk (non-oncogenic): HPV 6, 11 (cause genital warts/condylomata, not cancer)
Key points:
- The majority of people will clear HPV — the problem comes for those who are unable to clear HPV, causing persistent HPV [1][2]
- The progression from HPV infection → CIN → invasive cancer typically takes 10–20 years (this long window is what makes screening so effective)
- Not all CIN progresses: CIN 1 regresses spontaneously in ~60%; CIN 2 regresses in ~40%; CIN 3 has ~1% per year risk of progressing to invasive cancer if untreated
5.3 Molecular Pathophysiology — How HPV Causes Cancer
HPV infects the basal cells of the cervical epithelium (accessed through micro-abrasions, especially in the thin, metaplastic TZ epithelium).
The two key viral oncoproteins are:
- E6 binds to p53 (a tumour suppressor — the "guardian of the genome") via the E6AP ubiquitin ligase complex
- This targets p53 for ubiquitin-mediated proteasomal degradation
- Result: loss of p53 function → loss of apoptosis (damaged cells survive instead of dying) → loss of cell cycle arrest at G1/S checkpoint → accumulation of DNA mutations
- E7 binds to and inactivates retinoblastoma protein (pRb)
- pRb normally sequesters E2F transcription factor, preventing cell cycle progression
- When pRb is inactivated → E2F is released → uncontrolled cell proliferation (cells enter S phase without proper checkpoints)
- E7 also inactivates p21 and p27 (CDK inhibitors), further driving cell cycle
- In persistent infection, HPV DNA may integrate into the host cell genome
- This disrupts the viral E2 gene (which normally represses E6/E7 expression)
- Loss of E2 → uncontrolled, constitutive overexpression of E6 and E7 → accelerated oncogenesis
- HPV integration is a hallmark of progression from pre-invasive to invasive disease
- HPV E5 protein: enhances EGFR signalling, promotes immune evasion
- HPV evades immune detection by downregulating MHC class I expression, reducing antigen presentation
- Genomic instability accumulates over time → acquisition of further somatic mutations → invasive cancer
The Two-Hit Model of HPV Oncogenesis
Think of it simply:
- E6 knocks out p53 → cells can't die (loss of apoptosis)
- E7 knocks out Rb → cells can't stop dividing (loss of cell cycle control)
- Together: cells that should die don't, and cells that should stop dividing don't → uncontrolled proliferation with accumulated mutations → cancer
The HPV vaccination still works even if you have had sexual intercourse — although you cannot remove HPV from already-infected cells, it ensures that the new generations of cells cannot be infected. Then it relies on your body to shed off those infected cells with time, ensuring that you are protected for any future sexual encounter. [1][2]
- Current vaccines in use (as of 2025):
- Gardasil 9 (9-valent): HPV 6, 11, 16, 18, 31, 33, 45, 52, 58 — covers ~90% of cervical cancers
- Works by generating neutralising antibodies against L1 capsid protein (virus-like particles, VLPs — contain no viral DNA, so cannot cause infection)
- In Hong Kong, the government programme vaccinates girls (and increasingly boys) before sexual debut, but "catch-up" vaccination is recommended up to age 26 (and can be given up to 45 in some guidelines)
To reiterate: the TZ is where active squamous metaplasia occurs. The basal cells here are:
- Actively dividing (higher mitotic rate = more opportunities for HPV to insert itself)
- More accessible (thinner epithelium, micro-abrasions during intercourse)
- Expressing receptors that HPV exploits for entry (heparan sulfate proteoglycans, α6-integrin)
This is why almost all cervical cancers originate in the TZ.
6. Classification
| Type | Frequency | Key Features | HPV Association |
|---|---|---|---|
| Squamous Cell Carcinoma (SCC) | ~70–75% | Arises from squamous epithelium of ectocervix/TZ; preceded by CIN (squamous intraepithelial lesion); subtypes: keratinising, non-keratinising, basaloid, verrucous | Almost all HPV-related (HPV 16 most common) |
| Adenocarcinoma | ~20–25% (increasing) | Arises from glandular (columnar) epithelium of endocervix; preceded by AIS (adenocarcinoma in situ); harder to detect on Pap smear (endocervical location) | Majority HPV-related (HPV 18, 45 most common); but a small subset (~10-15% of adenocarcinomas) are HPV-independent |
| Adenosquamous carcinoma | ~3–5% | Mixed glandular and squamous differentiation | HPV-related |
| Neuroendocrine / Small cell carcinoma | ~1–2% | Very aggressive, high-grade; similar to small cell lung cancer | HPV-related |
| Other rare types | < 1% | Clear cell (associated with in-utero DES exposure — now very rare), serous, undifferentiated | Variable |
Clinical Pearl — Rising Adenocarcinoma
The proportion of adenocarcinoma is increasing, likely because:
- Screening (Pap smear) is better at detecting squamous lesions at the ectocervix than glandular lesions hidden in the endocervical canal
- Successful screening has reduced SCC incidence, so the relative proportion of adenocarcinoma rises
- HPV testing may help address this gap, as it can detect oncogenic HPV regardless of lesion location
This is a newer, clinically important classification:
- HPV-associated cervical carcinomas (~85–90%): driven by HPV; express p16 (a surrogate marker for HPV E7-mediated Rb pathway disruption — paradoxically, p16 is overexpressed because loss of Rb removes negative feedback on p16); better prognosis
- HPV-independent cervical carcinomas (~10–15%): typically adenocarcinomas (gastric-type, clear cell, mesonephric); p16 negative; TP53 mutations common; generally worse prognosis; not preventable by HPV vaccination
Pre-invasive lesions are classified as:
| Terminology | Histological Equivalent | Bethesda (Cytology) | Natural History |
|---|---|---|---|
| CIN 1 | Dysplasia confined to lower 1/3 of epithelium | LSIL (Low-grade Squamous Intraepithelial Lesion) | ~60% regress spontaneously; ~10% progress to CIN 3 |
| CIN 2 | Dysplasia in lower 2/3 of epithelium | HSIL (High-grade Squamous Intraepithelial Lesion) | ~40% regress; ~20% progress to CIN 3 |
| CIN 3 / Carcinoma in situ | Full-thickness dysplasia (but basement membrane intact — NOT yet invasive) | HSIL | ~1% per year progress to invasive cancer if untreated |
| AIS | Adenocarcinoma in situ — glandular equivalent of CIN 3 | AGC / AIS | Precursor of invasive adenocarcinoma |
The key distinction: CIN/AIS = pre-invasive (basement membrane intact); invasive cancer = basement membrane breached (can now invade stroma, lymphatics, blood vessels).
Cervical cancer is one of the few cancers that is clinically staged by FIGO, although the 2018 revision now allows incorporation of imaging and pathological findings.
| Stage | Description |
|---|---|
| IA | Microscopic invasion only (diagnosed by microscopy); IA1: stromal invasion ≤ 3mm depth; IA2: invasion > 3mm but ≤ 5mm depth |
| IB | Clinically visible or microscopic lesion > stage IA; IB1: ≤ 2cm; IB2: > 2cm but ≤ 4cm; IB3: > 4cm |
| IIA | Extends beyond cervix to upper 2/3 vagina, no parametrial involvement; IIA1: ≤ 4cm; IIA2: > 4cm |
| IIB | Parametrial involvement (cardinal/uterosacral ligaments invaded — this is a critical cutoff; parametrial involvement precludes primary surgery in most protocols) |
| IIIA | Extends to lower 1/3 vagina |
| IIIB | Extends to pelvic sidewall AND/OR causes hydronephrosis/non-functioning kidney |
| IIIC | Pelvic (IIIC1) or para-aortic (IIIC2) lymph node involvement (new in 2018 — now allows imaging/pathology to upstage) |
| IVA | Invasion of bladder or rectal mucosa (confirmed by biopsy) |
| IVB | Distant metastasis (lung, liver, bone, supraclavicular nodes) |
Key Staging Points for Exams
- Stage IIB (parametrial involvement) is the critical watershed: stages ≤ IIA are generally treated with primary surgery ± radiotherapy; stages ≥ IIB are primarily treated with concurrent chemoradiotherapy (CCRT)
- Stage IIIB includes hydronephrosis — always check renal function and imaging in cervical cancer
- The 2018 FIGO revision is significant because it now allows imaging (MRI, CT, PET-CT) and surgical/pathological findings (e.g., lymph node status) to be incorporated into staging
7. Clinical Features
7.1 Symptoms
The presentation depends heavily on stage. Early disease — not much [3]. This is because early/pre-invasive disease is confined to the epithelium, which has no blood vessels or nerves of its own.
| Symptom | Pathophysiological Basis |
|---|---|
| Asymptomatic (most common in early stage) | CIN and microinvasive cancer are confined to the epithelium/superficial stroma — no nerves stimulated, no significant vessels disrupted. This is why screening is so crucial |
| Postcoital bleeding (PCB) — the classic symptom [3] | The tumour at the TZ is friable (fragile, neovascular tissue with abnormal blood vessels). Mechanical trauma during intercourse disrupts these fragile vessels → bleeding. PCB is often the earliest symptom of invasive cervical cancer |
| Intermenstrual bleeding (IMB) | Same mechanism — friable tumour surface bleeds spontaneously between periods |
| Postmenopausal bleeding (PMB) | In postmenopausal women, any bleeding is abnormal and must be investigated; cervical cancer is one cause |
| Abnormal vaginal discharge | Tumour necrosis and secondary infection produce a watery, blood-stained, or foul-smelling discharge. The necrotic tumour surface is colonised by bacteria, producing a characteristic offensive odour |
High Yield — Postcoital Bleeding
Postcoital bleeding is the hallmark symptom of cervical cancer. [3] While most PCB is caused by benign conditions (cervical ectropion, polyps, cervicitis), it must always be investigated with speculum examination and cervical assessment. In a woman with risk factors, PCB = cervical cancer until proven otherwise.
| Symptom | Pathophysiological Basis |
|---|---|
| Back pain [3] | Tumour invades the parametrium, pelvic sidewall, or metastasises to para-aortic lymph nodes → compression/invasion of lumbosacral nerve plexus or vertebral metastases |
| Leg oedema (unilateral or bilateral) [3] | Tumour or enlarged lymph nodes compress or invade the iliac veins or lymphatics → obstructed venous/lymphatic return from the lower limb → oedema. Unilateral leg swelling in a woman with cervical cancer = think pelvic sidewall disease |
| Loin pain / renal failure | Tumour grows laterally into parametrium → compresses or invades the ureters (which run through the cardinal ligament, very close to the cervix — "water under the bridge") → hydronephrosis → renal failure. This is common and can be the presenting feature |
| Haematuria | Stage IVA — tumour invades the bladder mucosa |
| Rectal bleeding / tenesmus | Stage IVA — tumour invades the rectal mucosa |
| Pelvic pain | Invasion of nerves within the parametrium, obturator nerve, or sacral plexus |
| Urinary symptoms (frequency, urgency) | Tumour compresses or invades the bladder base; or vesicovaginal fistula forms |
| Fistulae (vesicovaginal, rectovaginal) | Advanced tumour erodes through into bladder or rectum — devastating complication causing continuous urinary or faecal incontinence; can also result from radiation therapy |
| Constitutional symptoms (weight loss, fatigue, anorexia) | Advanced/metastatic disease — cancer cachexia from systemic inflammatory mediators (TNF-α, IL-6) |
| Leg DVT / PE | Hypercoagulability of malignancy (Trousseau syndrome) + venous compression by tumour/lymphadenopathy |
7.2 Signs
| Sign | Pathophysiological Basis |
|---|---|
| Pallor / anaemia | Chronic vaginal bleeding → iron deficiency anaemia |
| Cachexia / weight loss | Advanced disease, cancer cachexia |
| Unilateral leg oedema | Lymphatic/venous obstruction by pelvic tumour or nodal disease |
| Supraclavicular lymphadenopathy (Virchow's node — left) | Distant lymphatic metastasis via the thoracic duct — indicates Stage IVB |
| Inguinal lymphadenopathy | Spread to inguinal nodes (less common; more typical if lower vagina involved) |
| Sign | Pathophysiological Basis |
|---|---|
| Visible cervical mass | Exophytic (cauliflower-like, protruding into vagina) or endophytic (barrel-shaped, expanding the cervix from within) or ulcerative (necrotic crater) growth at the cervix |
| Friable, contact bleeding | Tumour neovascularity — vessels are structurally abnormal and bleed easily on touch |
| Necrotic, foul-smelling tissue | Central tumour necrosis (outgrows its blood supply) with secondary bacterial infection |
| Normal-appearing cervix (in early/microinvasive disease or endocervical tumours) | The tumour may be too small to see, or may be hidden within the endocervical canal — emphasises the importance of cytology/HPV testing |
| Sign | Pathophysiological Basis |
|---|---|
| Enlarged, irregular, hard cervix | Tumour mass replacing normal cervical tissue |
| Parametrial thickening / nodularity | Tumour invasion of the cardinal and uterosacral ligaments — assessed by rectovaginal exam (critical for staging; "frozen pelvis" = completely fixed, bilateral parametrial involvement) |
| Fixed uterus / loss of mobility | Tumour has infiltrated surrounding structures, tethering the uterus |
| Pelvic sidewall fixation | Stage IIIB — tumour extends to the bony pelvis, causing complete fixation |
| Rectovaginal septum involvement | Tumour invading posteriorly — best assessed by rectal examination |
Clinical Approach — Always Do a Speculum
A common mistake is failing to perform a speculum examination in a woman with abnormal vaginal bleeding. Every woman with postcoital, intermenstrual, or postmenopausal bleeding needs a speculum exam to visualise the cervix. You cannot diagnose cervical cancer without looking at the cervix. A Pap smear alone is NOT sufficient to rule out cervical cancer if there is a visible lesion — if you see a suspicious lesion, BIOPSY it directly.
8. Pathophysiology of Clinical Features — Connecting the Dots
Let's tie together why each symptom/sign occurs, from the underlying biology:
- HPV infects TZ basal cells → E6/E7 → CIN 1 → CIN 2/3 → microinvasive cancer
- At this point, the disease is epithelial or minimally stromal — no symptoms
- As the tumour grows and develops its own blood supply (angiogenesis driven by VEGF), the abnormal vessels are fragile → postcoital bleeding (first symptom)
- Tumour necrosis begins → discharge
- Tumour invades deeper into cervical stroma → parametrium (cardinal and uterosacral ligaments) → Stage IIB
- Parametrial invasion compresses ureters ("water under the bridge" — ureter crosses under the uterine artery at the level of the cervix) → hydronephrosis → renal impairment → Stage IIIB
- Lateral extension to pelvic sidewall → compresses iliac vessels (venous oedema) and sacral/obturator nerves (pain, neuropathy) → leg oedema and back/pelvic pain
- Anterior invasion into bladder → haematuria, fistula → Stage IVA
- Posterior invasion into rectum → rectal bleeding, fistula → Stage IVA
- Lymphatic spread: parametrial → obturator → internal/external iliac → common iliac → para-aortic → mediastinal → supraclavicular
- Haematogenous spread (less common, late): lung > liver > bone
9. Relevant Etiology — Focus on Hong Kong
- While globally HPV 16 and 18 dominate, in Hong Kong and East Asia, HPV 52 and 58 are more prevalent than in Western populations
- This is clinically significant because the older bivalent (Cervarix) and quadrivalent (Gardasil) vaccines did not cover HPV 52/58; the 9-valent Gardasil 9 does cover these and is therefore preferred in Hong Kong
- The Cervical Screening Programme (CSP) recommends:
- Women aged 25–64 who have ever been sexually active
- First Pap smear, repeat at 1 year, then every 3 years if normal
- From 2024, Hong Kong has been transitioning to primary HPV testing as the recommended screening modality (in line with WHO 2021 guidelines), with cytology as triage for HPV-positive results
- HPV self-sampling is being explored to improve screening uptake among hard-to-reach populations
- Primary prevention: HPV vaccination (Gardasil 9) — government-funded for schoolgirls; recommended for boys as well
- Secondary prevention: Cervical screening (Pap smear / HPV testing) — early detection of CIN, treatment before progression to cancer
- Could it be prevented? Yes → vaccination [4] — but for those already infected, screening remains essential
High Yield Summary
Definition: Malignant neoplasm of the cervix, arising at the transformation zone (SCJ), causally linked to persistent high-risk HPV infection.
Epidemiology: 4th most common female cancer globally; median age 55 in HK; declining with screening and vaccination.
Risk Factors — Two Buckets:
- HPV acquisition: HPV infection, early sex, multiple partners, OCP use
- Impaired HPV clearance: smoking, immunosuppression, low socioeconomic status
- HPV is NECESSARY but NOT SUFFICIENT
Key Pathophysiology: HPV E6 degrades p53 (loss of apoptosis); E7 inactivates Rb (uncontrolled proliferation). HPV integration → constitutive E6/E7 expression → CIN → invasive cancer over 10–20 years.
Histology: SCC (~70–75%) > Adenocarcinoma (~20–25%) > Others. Adenocarcinoma rising in proportion.
Classification: CIN 1/2/3 → invasive. FIGO staging 2018 (incorporates imaging/pathology). Stage IIB (parametrial involvement) = watershed for treatment.
Clinical Features:
- Early: asymptomatic or postcoital bleeding
- Late: back pain, leg oedema, hydronephrosis, fistulae, constitutional symptoms
- Always perform speculum examination in abnormal vaginal bleeding
HPV Vaccination: Works even after sexual debut (protects new cells; body sheds infected cells over time). Gardasil 9 preferred in HK (covers HPV 52, 58).
Active Recall — Cervical Cancer: Definition, Epidemiology, Risk Factors, Etiology, Pathophysiology, Classification and Clinical Features
[1] Lecture slides: Block C - Abnormal vaginal bleeding_ gynaecological cancer.pdf (p17) [2] Lecture slides: Block C - O&G Theme Case 2.docx.pdf (p8) [3] Lecture slides: GC 112. Abnormal vaginal bleeding Gynaecological cancer.pdf (p11, slides 21–22) [4] Lecture slides: Block C - O&G Theme Case 2.docx.pdf (p8, Q6)
Differential Diagnosis of Cervical Cancer
The differential diagnosis (DDx) of cervical cancer is really the differential of its presenting symptoms and signs. The most common presentations you need to differentiate are:
- Abnormal vaginal bleeding (postcoital, intermenstrual, postmenopausal)
- A visible cervical lesion on speculum examination
- Abnormal vaginal discharge
The clinical reasoning here is: you see a patient with one or more of these features — what could it be other than cervical cancer? And how do you systematically work through it?
Per-vaginal bleeding — separate answer into benign / malignant. Cancer is not the commonest cause → many many more benign causes. [1]
Classify based on anatomy → start from bottom, and move upwards: Vagina → cervix → endometrium → ovaries. [1]
This anatomical approach is the safest way to avoid missing diagnoses in an exam or clinical setting. Let's build the DDx systematically.
A. Differential Diagnosis by Anatomical Site
| Condition | Key Differentiating Features | Why It Mimics Cervical Cancer |
|---|---|---|
| Cervical ectropion (erosion) | Very common, especially in young women on OCP or pregnant; columnar epithelium everts onto ectocervix, appears red and velvety on speculum; bleeds on contact | Causes PCB and looks red/friable on speculum — but it is a physiological finding, not neoplastic. The columnar epithelium is simply more delicate than squamous |
| Cervical polyp | Pedunculated, smooth, red/purple mass protruding from os; benign endocervical glandular overgrowth; easy to see on speculum | Causes PCB and IMB; visible lesion at cervix — but smooth, not irregular/necrotic. Almost always benign (< 1% malignant) |
| Cervicitis (Chlamydia, Gonorrhoea, HSV) | Purulent discharge, contact bleeding, mucopurulent endocervical discharge; history of STI risk; cervix may appear inflamed/oedematous | Causes PCB and discharge; cervix looks inflamed — but there is no mass. Swabs and NAAT testing differentiate |
| Cervical intraepithelial neoplasia (CIN) | Pre-invasive; usually detected on screening (abnormal Pap/HPV), not visible to naked eye (requires colposcopy with acetic acid/Lugol's iodine to visualise) | Doesn't usually cause symptoms — but it is the precursor to cervical cancer. The distinction between CIN 3 and microinvasive cancer requires histology |
| Nabothian cysts | Retention cysts of endocervical glands covered by squamous metaplasia; smooth, rounded, translucent/yellowish bumps on cervix | May look like a cervical lesion on speculum but clearly cystic, smooth, non-friable — entirely benign |
| Cervical fibroid (leiomyoma) | Smooth, firm, round mass at cervix; rare location for fibroids | Pelvic mass at the cervix — but smooth, regular, without ulceration or necrosis |
| Condition | Key Differentiating Features |
|---|---|
| Vaginal cancer (primary — rare) | Usually SCC in elderly women; may present with PV bleeding and visible vaginal mass; distinguished by location (vaginal wall, not cervix) |
| Vaginal atrophy (atrophic vaginitis) | Postmenopausal; thin, pale, friable vaginal epithelium due to oestrogen deficiency; causes PMB, dyspareunia, discharge; no discrete mass |
| Vaginal trauma | History of intercourse, foreign body, or assault; visible laceration |
| Vaginal infections (Candida, BV, Trichomonas) | Discharge predominates; no mass; characteristic discharge features |
| Condition | Key Differentiating Features |
|---|---|
| Endometrial cancer | Most common cause of PMB that you must exclude; typically postmenopausal bleeding in obese women with metabolic syndrome; no visible cervical lesion (bleeding comes from above); diagnosed by endometrial biopsy/hysteroscopy |
| Endometrial polyp | IMB, PMB; diagnosed on ultrasound/hysteroscopy; cervix looks normal |
| Endometrial hyperplasia | Irregular/heavy bleeding in perimenopausal women; associated with unopposed oestrogen; diagnosed on biopsy |
| Dysfunctional uterine bleeding / Anovulatory bleeding | Most common cause of endometrial bleeding is irregular ovulation causing irregular periods [1]; reproductive age; no structural lesion |
| Uterine fibroids (leiomyoma) | Heavy menstrual bleeding (menorrhagia), not typically PCB; enlarged, irregular uterus on palpation; diagnosed on ultrasound |
| Adenomyosis | Heavy, painful periods (dysmenorrhoea + menorrhagia); diffusely enlarged, tender uterus; MRI is best imaging |
| Condition | Key Differentiating Features |
|---|---|
| Ovarian cancer | Rarely causes PV bleeding (more commonly ascites, bloating, pelvic mass); CA-125 elevated in epithelial ovarian cancer |
| Ruptured ovarian cyst / ectopic pregnancy | Acute presentation with pain ± bleeding; positive β-hCG in ectopic; haemodynamic instability if ruptured |
Don't forget about pregnancy → especially for teenage girls [5]
| Condition | Key Differentiating Features |
|---|---|
| Threatened / incomplete miscarriage | Positive pregnancy test; PV bleeding with or without pain; products of conception may be visible at os |
| Ectopic pregnancy | Positive β-hCG, unilateral pelvic pain, PV bleeding; potentially life-threatening |
| Gestational trophoblastic disease | Very high β-hCG; "snowstorm" on ultrasound; vaginal bleeding in early pregnancy |
Always Do a Pregnancy Test
In any woman of reproductive age with abnormal vaginal bleeding, always exclude pregnancy first with a urine or serum β-hCG before proceeding with further investigation. Missing an ectopic pregnancy can be fatal.
| Condition | Key Features |
|---|---|
| Urethral / bladder pathology | Haematuria mistaken for PV bleeding; urinalysis differentiates; bladder cancer presents with painless haematuria [6] |
| Rectal / anal pathology | Haemorrhoids, colorectal cancer — rectal bleeding misinterpreted as vaginal; rectal exam and proctoscopy differentiate |
| Coagulopathy | Anticoagulant use, ITP, von Willebrand disease — may exacerbate or cause PV bleeding; check coagulation profile |
When you see something abnormal on the cervix during speculum exam, the DDx of the visible lesion is narrower:
| Benign | Malignant / Pre-malignant |
|---|---|
| Cervical ectropion | Cervical cancer (SCC, adenocarcinoma) |
| Cervical polyp | CIN (requires colposcopy to see) |
| Nabothian cyst | Cervical lymphoma (very rare) |
| Cervical fibroid | Cervical sarcoma (very rare) |
| Condylomata acuminata (genital warts — HPV 6/11) | Metastasis to cervix from other primary (extremely rare) |
| Endometriosis of cervix (rare) |
Key Principle — Biopsy Any Suspicious Cervical Lesion
Biopsy a must for suspicious lesions [3][7]. A Pap smear is a screening test, not a diagnostic one. If you see a visible suspicious lesion on the cervix (irregular, friable, ulcerated, necrotic), you must biopsy it directly — do NOT rely on cytology alone. Cytology can miss invasive cancer because the surface cells may be necrotic and the smear may be inadequate.
| Feature | Cervical Cancer | Cervical Ectropion | Cervical Polyp | Endometrial Cancer |
|---|---|---|---|---|
| Age | Median 55 [3] | Young, reproductive age | Any age (perimenopausal) | Postmenopausal (60–70s) |
| Bleeding pattern | Postcoital bleeding [3] | PCB (light) | IMB, PCB | PMB (not PCB) |
| Speculum appearance | Irregular, friable mass; ulcerated/necrotic; bleeds on touch | Smooth, red area around os | Smooth, pedunculated, red/purple | Cervix usually normal; blood from os |
| Discharge | Foul-smelling, blood-stained | Mucoid | Minimal | Watery/blood-stained from uterus |
| Risk factors | HPV, smoking, immunosuppression | OCP, pregnancy | None specific | Obesity, diabetes, unopposed oestrogen, tamoxifen |
| Diagnosis | Biopsy of lesion | Clinical + Pap smear | Polypectomy + histology | Endometrial biopsy / hysteroscopy |
Tumour markers for cervical cancer → SCC marker. CA-125 is for ovarian cancer, and adenocarcinoma in general → but in CA cervix, the most common cell type is squamous cell carcinoma (80%), so the only situation you would take CA-125 is when a biopsy has been taken, and the pathology for CA cervix comes back as adenocarcinoma. [7]
| Tumour Marker | Associated Cancer | When Relevant in Cervical Cancer DDx |
|---|---|---|
| SCC antigen | Squamous cell carcinomas (cervix, lung, oesophagus, H&N) | Primary tumour marker for cervical SCC; used for monitoring, not screening [7][8] |
| CA-125 | Ovarian cancer, adenocarcinomas | Only relevant in cervical adenocarcinoma (not SCC) [7] |
| β-hCG | Pregnancy, GTD, germ cell tumours | Exclude pregnancy/GTD in reproductive age women [8] |
| CEA | Colorectal, GI cancers | Not relevant in cervical cancer DDx unless considering GI primary [8] |
| CA 19-9 | Pancreatic, biliary, GI cancers | Not relevant for cervical cancer |
- Cervical ectropion: extremely common in young HK women on OCP — the most frequent benign cause of PCB. Don't over-investigate, but always perform a smear and ensure screening is up to date
- Endometrial cancer: the most common gynaecological malignancy in Hong Kong (more common than cervical cancer). Always consider in PMB. The key distinguishing feature: cervix looks normal, bleeding comes from above
- Cervicitis from Chlamydia/Gonorrhoea: STI rates are rising in HK, especially among young adults. A mucopurulent cervical discharge with contact bleeding can mimic early cervical cancer — do NAAT swabs
High Yield Summary — DDx of Cervical Cancer
Approach: Anatomical — vagina → cervix → endometrium → ovaries. Separate benign vs. malignant.
Most important benign mimics of PCB: cervical ectropion (most common), cervical polyp, cervicitis.
Most important malignant DDx: endometrial cancer (PMB with normal cervix), vaginal cancer (rare).
Always exclude pregnancy in reproductive-age women.
Key rule: If there is a visible suspicious cervical lesion → BIOPSY. Do not rely on Pap smear alone.
Tumour markers: SCC antigen for SCC-type cervical cancer; CA-125 only if adenocarcinoma confirmed on histology.
Imaging: MRI is the best imaging modality for cervical cancer (local spread assessment); PET-MRI if available.
Active Recall — Differential Diagnosis of Cervical Cancer
References
[1] Lecture slides: Block C - Abnormal vaginal bleeding_ gynaecological cancer.pdf (p1) [3] Lecture slides: GC 112. Abnormal vaginal bleeding Gynaecological cancer.pdf (p11, slides 21–22) [5] Lecture slides: Block C - Pelvic mass_ ovarian cancer and cysts; uterine fibroid; pelvic imaging.pdf (p17) [6] Senior notes: Ryan Ho Urogenital.pdf (p153) [7] Lecture slides: Block C - Abnormal vaginal bleeding_ gynaecological cancer.pdf (p21) [8] Senior notes: Maksim Medicine Notes.pdf (p337)
Diagnosis of Cervical Cancer — Criteria, Algorithm, and Investigations
Before diving in, understand that there are two fundamentally different clinical scenarios that lead to the diagnosis of cervical cancer:
- Symptomatic patient (e.g., postcoital bleeding, visible lesion on speculum) → direct biopsy of the lesion
- Asymptomatic patient detected through screening (abnormal Pap smear / HPV test) → colposcopy + directed biopsy
The endpoint is the same: histopathological confirmation on biopsy. There is no blood test, imaging study, or tumour marker that diagnoses cervical cancer. The diagnosis is always histological.
A. Pathological Diagnosis — Two Complementary Modalities
Two aspects of pathological diagnosis [9]:
- Looking at the abnormal cells → obtained by cervical smear (cytology) [9]
- Looking at the abnormal architecture / invasion → obtained by cervical biopsy (histopathology) [9]
This distinction is critical:
| Cytology (Cervical Smear / Pap Smear) | Histopathology (Biopsy) | |
|---|---|---|
| What it examines | Individual cells scraped from the cervix | Tissue architecture — how cells are organised, whether basement membrane is intact/breached |
| What it can tell you | Whether cells look abnormal (dyskaryosis / intraepithelial lesion) | Whether there is CIN, AIS, or invasive cancer (tumour invading through basement membrane into stroma) |
| Limitation | Cannot determine invasion — you can't see tissue architecture from loose cells | Requires a procedure (biopsy, cone, LLETZ) |
| Classification system | Bethesda System [9] | WHO Classification [9] |
| Role | Screening (population-level detection of abnormalities) | Diagnosis (definitive confirmation of disease) |
| Bethesda Category | Meaning | Next Step |
|---|---|---|
| NILM (Negative for Intraepithelial Lesion or Malignancy) | Normal | Routine screening |
| ASC-US (Atypical Squamous Cells of Undetermined Significance) | Mildly abnormal cells, unclear significance; most common abnormal result | HPV triage (if HPV+, colposcopy; if HPV−, repeat in 12 months) |
| ASC-H (Atypical Squamous Cells, cannot exclude HSIL) | More suspicious than ASC-US; ~40% have CIN 2/3 on biopsy | Colposcopy |
| LSIL (Low-grade Squamous Intraepithelial Lesion) | Corresponds to CIN 1 / HPV cytopathic effect (koilocytosis) | HPV triage or colposcopy |
| HSIL (High-grade Squamous Intraepithelial Lesion) | Corresponds to CIN 2/3; significant risk of underlying invasive cancer | Colposcopy (urgent) |
| SCC | Squamous cell carcinoma on cytology | Urgent referral — biopsy to confirm |
| AGC (Atypical Glandular Cells) | Abnormal glandular cells — concerning for AIS or adenocarcinoma; harder to detect | Colposcopy + endocervical curettage ± endometrial sampling |
| AIS (Adenocarcinoma in situ) | Glandular pre-cancer | Excisional procedure (cone biopsy) |
- CIN 1 / CIN 2 / CIN 3 (squamous pre-invasive)
- AIS (glandular pre-invasive)
- Invasive SCC / Adenocarcinoma / Adenosquamous / Neuroendocrine / Others
- HPV-associated vs. HPV-independent (WHO 2020 classification)
Cervical cancer does not have a rigid "diagnostic criteria" checklist like, say, rheumatoid arthritis. Instead, the diagnosis rests on:
| Criterion | Detail |
|---|---|
| 1. Histological confirmation (mandatory) | Biopsy showing invasive carcinoma — tumour cells breaching the basement membrane and invading cervical stroma |
| 2. Specifiable histological type | SCC, adenocarcinoma, adenosquamous, neuroendocrine, etc. (per WHO classification) |
| 3. HPV status (increasingly important) | p16 immunohistochemistry as surrogate for HPV-driven carcinogenesis; HPV genotyping if available |
| 4. FIGO Stage (clinical + imaging + pathological) | Determined by clinical exam, imaging (MRI, PET-CT), and surgical/pathological findings (2018 FIGO) |
The minimum requirement for diagnosis = biopsy-proven invasive cervical carcinoma.
For microinvasive disease (Stage IA), the diagnosis specifically requires:
- Excisional biopsy (cone biopsy / LLETZ), NOT punch biopsy — because you need to assess depth and width of invasion and confirm clear margins
- Punch biopsy cannot measure depth of invasion accurately
Punch Biopsy vs. Excisional Biopsy
A common error: a punch biopsy showing "invasive squamous cell carcinoma" does NOT tell you the stage. To determine whether the cancer is truly microinvasive (Stage IA1 ≤ 3mm; IA2 3–5mm), you need an excisional specimen (cone/LLETZ) to measure the maximum depth and horizontal extent of stromal invasion. Punch biopsies only confirm the presence of invasion, not its extent.
C. Investigation Modalities — Systematic Approach
Investigations are divided into two purposes [3]:
- For diagnosis — Take a biopsy
- For plan of management — Blood tests (CBP, RFT, LFT), tumour markers, imaging (CT / MRI / PET-CT) to assess renal tract / extent of spread / lymph node involvement
Let's go through each systematically.
C1. Investigations for Diagnosis
The very first step. Allows direct visualisation of the cervix.
| Finding | Interpretation |
|---|---|
| Exophytic/cauliflower-like mass | Likely invasive cancer — biopsy directly |
| Ulcerative/necrotic lesion | Likely invasive cancer — biopsy directly |
| Barrel-shaped, expanded cervix | Endophytic (endocervical) tumour — may need endocervical curettage |
| Smooth red area around os | Likely ectropion — but still do smear/HPV test |
| Normal-appearing cervix | Cancer not excluded — may be microinvasive or endocervical; proceed with smear/HPV |
Common gynaecological examination: cervical smear / Pap smear → if positive, refer to colposcopy → magnifying cervix to have a look, then take a cervical biopsy [10]
Image showing the magnified cervix seen on colposcopy → looking at cervical os; if cervical os is circle, then nulliparous woman; if cervical os shape is a line, suggestive of parous woman [10]
- Pap smear: cells collected from the TZ using a spatula and cytobrush; processed as liquid-based cytology (LBC) — reported using the Bethesda System
- HPV test: PCR-based detection of high-risk HPV DNA/RNA from the same sample
- In Hong Kong, the screening programme is transitioning to primary HPV testing (HPV test first → if positive, cytology triage)
- Important: a Pap smear is a screening test — if there is a visible suspicious lesion, you go straight to biopsy, not smear
Colposcopy ("colpo" = vagina/cervix, "scopy" = looking) — a magnified examination of the cervix using a colposcope (binocular magnifying device, 6–40× magnification).
Procedure:
- Speculum inserted
- Cervix visualised under magnification
- Acetic acid (3–5%) applied → abnormal epithelium turns acetowhite (because acetic acid coagulates nuclear proteins; dysplastic cells have higher nuclear-to-cytoplasmic ratio, so more protein → more whitening)
- Lugol's iodine (Schiller's test) applied → normal squamous epithelium stains dark brown/mahogany (contains glycogen which binds iodine); dysplastic/columnar epithelium remains unstained (Schiller-positive) (dysplastic cells lack glycogen)
- Directed punch biopsies taken from the most abnormal-appearing areas
- Endocervical curettage (ECC) performed if the TZ is not fully visualised or if there is suspicion of endocervical disease
| Colposcopic Finding | Interpretation |
|---|---|
| Acetowhite epithelium (thin, flat) | Suggests low-grade dysplasia (CIN 1) |
| Dense acetowhite, coarse mosaic/punctation | Suggests high-grade dysplasia (CIN 2/3) |
| Atypical vessels, irregular surface, ulceration, exophytic mass | Suggests invasive cancer |
| Lugol's non-staining (Schiller-positive) area | Abnormal epithelium (dysplastic or columnar — not specific) |
| Type | When Used | What It Tells You |
|---|---|---|
| Punch biopsy (colposcopy-directed) | Visible lesion or colposcopic abnormality | Confirms presence of CIN or invasive cancer; cannot accurately measure depth of invasion |
| LLETZ / LEEP (Large Loop Excision of the Transformation Zone) | Diagnostic AND therapeutic for CIN; also used as excisional biopsy for suspected microinvasion | Provides the entire TZ as a specimen; allows assessment of depth, margins, and LVSI |
| Cone biopsy (cold-knife conization) | Suspected microinvasive disease, adenocarcinoma/AIS (because glandular lesions extend higher into canal), discrepancy between cytology and colposcopy | Provides a cone-shaped specimen of cervix including endocervical canal; gold standard for assessing microinvasion |
| EUA + biopsy (Examination Under Anaesthesia) | Large/advanced lesions; assessing parametrial involvement for staging | Allows thorough bimanual and rectovaginal examination + generous biopsy of tumour |
C2. Investigations for Staging and Management Planning
Once the diagnosis is confirmed histologically, the next step is staging — determining how far the cancer has spread. This dictates treatment.
Blood test: CBP, RFT, LFT [3]
| Test | Rationale / Key Findings |
|---|---|
| CBP (Complete Blood Picture) | Anaemia from chronic PV bleeding (iron deficiency pattern: microcytic, hypochromic); thrombocytopenia if bone marrow infiltration (very late); leucocytosis if infection/necrosis |
| RFT (Renal Function Tests) — urea, creatinine, electrolytes | Critical: cervical cancer commonly causes ureteric obstruction → hydronephrosis → renal impairment. Elevated creatinine = possible bilateral ureteric obstruction → Stage IIIB. Must be assessed before any nephrotoxic chemotherapy (e.g., cisplatin) |
| LFT (Liver Function Tests) | Elevated ALP/GGT → possible liver metastases or bone metastases. Elevated bilirubin/transaminases → liver parenchymal involvement |
| Coagulation profile | Baseline before surgery; DIC screen in advanced disease |
| Iron studies | To confirm iron deficiency if anaemic |
Tumour markers for cervical cancer → SCC marker [7]
CA-125 is for ovarian cancer, and adenocarcinoma in general → but in CA cervix, the most common cell type is squamous cell carcinoma (80%), so the only situation you would take CA-125 is when a biopsy has been taken, and the pathology for CA cervix comes back as adenocarcinoma [7]
| Marker | When to Use | Interpretation |
|---|---|---|
| SCC antigen (Squamous Cell Carcinoma antigen) | All cervical SCC (the majority) | Elevated in ~60% of SCC; useful for monitoring treatment response and detecting recurrence, not for screening or primary diagnosis. Level correlates with tumour volume and stage |
| CA-125 | Cervical adenocarcinoma only (after histology confirmed) | Elevated in adenocarcinoma; useful for monitoring; not indicated in SCC |
| CEA | Occasionally in adenocarcinoma | Less commonly used |
Tumour Markers Are Not Diagnostic
Tumour markers (SCC Ag, CA-125) are never used to diagnose cervical cancer. They are used for: (1) baseline pre-treatment, (2) monitoring treatment response, (3) detecting recurrence during follow-up. A normal tumour marker does NOT exclude cancer.
What is the best imaging modality for cervical cancer? [7]
Similar to rectal cancer, important for cervical cancer to know extent of local spread → has implications on whether surgery can be offered [7]
So MRI is the best modality for cervical cancer, as apart from local invasion it is also pretty good at detecting metastatic lesions / lymph node involvement [7]
What is done in HKU: MRI abdomen + pelvis done first, along with chest X-ray. PET-MR if you have the money [7]
| Imaging Modality | Role | Key Findings |
|---|---|---|
| MRI Pelvis + Abdomen (BEST modality) | Primary staging modality — gold standard for assessing local extent | T2-weighted: tumour appears as intermediate-high signal mass replacing the normal low-signal cervical stroma. Assesses: (1) tumour size, (2) parametrial invasion (disruption of the dark stromal ring = parametrial involvement → Stage IIB), (3) vaginal extension, (4) bladder/rectal invasion, (5) pelvic sidewall involvement, (6) lymphadenopathy (pelvic and para-aortic), (7) hydronephrosis. DWI (Diffusion-Weighted Imaging): tumour shows restricted diffusion (high cellularity) — enhances tumour delineation |
| Chest X-ray | Baseline assessment for lung metastases | Cannonball metastases, pleural effusion, lymphangitis carcinomatosa [11] |
| CT Chest/Abdomen/Pelvis | Supplement to MRI — better for detecting distant metastases (lung, liver, bone, distant lymph nodes) | Lymphadenopathy (> 1cm short axis = suspicious); hydronephrosis; liver/lung metastases. Less accurate than MRI for local staging (poor soft tissue contrast in pelvis) |
| PET-CT or PET-MRI | Best for detecting lymph node metastases and distant disease | 18F-FDG-avid lesions [12]; superior to CT alone for detecting involved lymph nodes (sensitivity ~75–95% vs. ~50% for CT); excellent for detecting occult distant metastases; increasingly used for treatment planning (radiotherapy field design). PET-MR combines the local staging superiority of MRI with the metabolic/distant staging of PET [7] |
| Ultrasound (Transvaginal / Transrectal) | Limited role; occasionally used to assess tumour size, parametrial invasion; operator-dependent | Hypoechoic cervical mass; assessing blood flow with Doppler |
| IVU (Intravenous Urography) | Historically used to assess ureteric obstruction; now largely replaced by CT/MRI | Hydronephrosis, ureteric deviation/obstruction |
The key staging question in cervical cancer is: has the tumour invaded the parametrium? This is because parametrial invasion (Stage IIB) is the watershed between surgical and non-surgical management.
- The parametrium is the connective tissue surrounding the cervix (cardinal and uterosacral ligaments), containing the uterine artery, ureter, and lymphatic channels
- On MRI T2-weighted images, the normal cervical stroma appears as a dark (low-signal) ring around the cervix
- An intact dark stromal ring = parametrium NOT invaded = potentially resectable
- A disrupted dark stromal ring with tumour signal extending beyond = parametrial invasion = Stage IIB = primary chemoradiotherapy (not surgery)
- CT cannot reliably distinguish tumour from normal cervical stroma (poor soft tissue contrast in the pelvis)
- This is exactly analogous to why MRI is best for rectal cancer (assessing mesorectal fascia involvement)
| Investigation | When | Purpose |
|---|---|---|
| Cystoscopy | If anterior extension suspected (Stage IVA) | Confirm bladder mucosal invasion — must see bullous oedema or tumour on the bladder mucosa with biopsy confirmation. Bullous oedema alone does not equal Stage IVA |
| Proctoscopy / Sigmoidoscopy | If posterior extension suspected (Stage IVA) | Confirm rectal mucosal invasion — requires biopsy confirmation |
| EUA (Examination Under Anaesthesia) | Part of clinical staging, especially for advanced disease | Thorough bimanual + rectovaginal examination to assess parametrial/pelvic sidewall involvement, vaginal extension. Done under anaesthesia for proper muscle relaxation and patient comfort |
| Bone scan / Bone MRI | If bone pain or elevated ALP | Assess for bone metastases |
| Brain MRI | If neurological symptoms | Assess for brain metastases (rare) |
The pathology report on the biopsy/excision specimen provides critical information:
| Parameter | Clinical Significance |
|---|---|
| Histological type | SCC vs. adenocarcinoma vs. others — determines tumour marker choice (SCC Ag vs. CA-125), and has prognostic implications |
| Grade (well/moderately/poorly differentiated) | Higher grade = more aggressive behaviour |
| Depth of stromal invasion (in mm) | Determines Stage IA1 vs. IA2 vs. IB (on excisional specimen only) |
| Horizontal extent | Contributes to staging of microinvasive disease |
| Lymphovascular space invasion (LVSI) | Present = higher risk of lymph node metastasis; influences decision for lymphadenectomy |
| Margin status | Positive margins on cone/LLETZ = need for re-excision or further surgery |
| p16 immunostaining | Surrogate for HPV-driven carcinogenesis (diffuse strong block-positive p16 = HPV-associated); HPV-independent tumours are p16-negative and have worse prognosis |
| Stage | How It Is Determined |
|---|---|
| IA1 / IA2 | Excisional biopsy (cone/LLETZ) — microscopic measurement of invasion depth (≤ 3mm = IA1; > 3–5mm = IA2) |
| IB1 / IB2 / IB3 | Clinical exam + MRI — tumour size (≤ 2cm / > 2–4cm / > 4cm) |
| IIA | MRI + Clinical exam — upper 2/3 vaginal involvement, no parametrial invasion |
| IIB | MRI (disrupted stromal ring) + EUA (parametrial thickening/nodularity on rectovaginal exam) |
| IIIA | Clinical exam — lower 1/3 vaginal involvement |
| IIIB | MRI/CT — hydronephrosis or non-functioning kidney; pelvic sidewall involvement on EUA |
| IIIC1 / IIIC2 | PET-CT/MRI or surgical pathology — pelvic (IIIC1) or para-aortic (IIIC2) lymph node involvement |
| IVA | Cystoscopy/proctoscopy with biopsy — confirmed bladder/rectal mucosal invasion |
| IVB | CT/PET-CT — distant metastases (lung, liver, bone, supraclavicular nodes) |
2018 FIGO — Game Changer
The 2018 FIGO revision for cervical cancer was a major update: it now allows imaging and pathological findings (especially lymph node status on PET-CT or surgical assessment) to formally upstage the disease (Stage IIIC). Previously, cervical cancer staging was purely clinical. This reflects the prognostic importance of nodal disease and modern imaging capabilities.
| Category | Investigation | Purpose | Key Findings |
|---|---|---|---|
| Diagnostic | Speculum exam | Visualise cervix | Mass, ulcer, bleeding, normal |
| Pap smear / HPV test | Screen for abnormalities | Bethesda classification; HPV+ or − | |
| Colposcopy + biopsy | Magnified cervix exam + tissue | Acetowhite, mosaic, atypical vessels; CIN/cancer on histology | |
| Cone biopsy / LLETZ | Excisional diagnosis | Depth of invasion, margins, LVSI | |
| Bloods | CBP | Anaemia assessment | Microcytic anaemia (iron deficiency from chronic bleeding) |
| RFT | Renal function (ureteric obstruction?) | Elevated creatinine → hydronephrosis → Stage IIIB | |
| LFT | Liver metastases? | Elevated ALP, GGT | |
| Tumour markers | SCC antigen | SCC cervical cancer | Monitoring response/recurrence |
| CA-125 | Cervical adenocarcinoma only | Only if adenocarcinoma on histology | |
| Imaging | MRI pelvis + abdomen | Local staging (best) | Tumour size, parametrial invasion, vaginal/bladder/rectal extension, nodes, hydronephrosis |
| CXR | Lung metastases | Cannon-ball mets, effusion | |
| PET-CT / PET-MRI | Nodal + distant staging | FDG-avid nodes, distant metastases | |
| CT C/A/P | Distant staging supplement | Nodes, liver, lung, bone | |
| Endoscopy | Cystoscopy / Proctoscopy | Stage IVA assessment | Mucosal invasion (biopsy-proven) |
| Clinical | EUA | Parametrial/sidewall assessment | Parametrial thickening, fixed pelvis |
High Yield Summary — Diagnosis of Cervical Cancer
- Diagnosis is ALWAYS histological — biopsy is mandatory for any suspicious cervical lesion.
- Cytology (Pap smear, Bethesda System) = screening. Histopathology (biopsy, WHO) = diagnosis.
- Punch biopsy confirms cancer; excisional biopsy (cone/LLETZ) is needed to assess depth of invasion for microinvasive disease.
- Staging workup: CBP, RFT, LFT + SCC antigen (or CA-125 for adenocarcinoma) + MRI pelvis/abdomen (best modality) + CXR ± PET-CT/MRI
- MRI is best for local staging (parametrial invasion — disrupted dark stromal ring on T2W). PET-CT/MRI is best for nodal and distant metastases.
- 2018 FIGO staging now incorporates imaging and pathology (especially for nodal disease — Stage IIIC).
- RFT is critical — hydronephrosis from ureteric obstruction is common and upstages to IIIB.
Active Recall — Diagnosis and Investigations for Cervical Cancer
References
[3] Lecture slides: GC 112. Abnormal vaginal bleeding Gynaecological cancer.pdf (p13, slide 25) [7] Lecture slides: Block C - Abnormal vaginal bleeding_ gynaecological cancer.pdf (p21) [9] Lecture slides: Block C - Abnormal cervical smear_ cervical cancer; cancer screening.pdf (p11) [10] Lecture slides: Block C - Abnormal vaginal bleeding_ gynaecological cancer.pdf (p10) [11] Senior notes: Ryan Ho Respiratory.pdf (p151) [12] Senior notes: Ryan Ho Diagnostic Radiology.pdf (p74)
Management of Cervical Cancer — Algorithm, Treatment Modalities, Indications and Contraindications
Before we get into the specifics, let's establish the overarching logic of cervical cancer management. Every treatment decision flows from one central question: how far has the cancer spread?
Treatment modalities in cancer: Surgery, Radiotherapy, Chemotherapy, Targeted therapy / immunotherapy [13]
The management of cervical cancer is then dictated by stage, which determines the feasibility of each modality:
- Surgery — for early disease (e.g., Stage 1)
- Radiotherapy — for early disease if surgery not suitable; for late disease (Stage 2 or above)
- Chemotherapy — in combination with radiotherapy (chemo-irradiation)
- For recurrence — targeted therapy: Bevacizumab, used in combination with chemo
Surgery only suitable for early disease (Stage 1 disease). Beyond cervix, or tumour size beyond 4cm, cannot do surgery → will choose radiotherapy. [14]
The Stage IIB Watershed — The Single Most Important Concept
Stage IIB (parametrial invasion) is the critical dividing line:
- ≤ Stage IIA → Primary surgery is the preferred approach (curative resection possible)
- ≥ Stage IIB → Primary concurrent chemoradiotherapy (CCRT) is standard (surgery cannot achieve clear margins when parametrium is involved, and dual modality — surgery + radiotherapy — increases morbidity without improving survival)
This is why MRI assessment of parametrial invasion is so pivotal to management.
B. Detailed Treatment Modalities
B1. Surgery
Surgery is the preferred modality for early-stage cervical cancer because it allows:
- Preservation of ovarian function — ovaries are not removed, since ovarian spread in usual type of HPV-associated cervical cancer is rare [14][15]
- Avoidance of long-term morbidities of radiotherapy — since surgery is curative for early disease, do not require adjuvant radiotherapy [14][15]
- Complete pathological assessment (lymph node status, margins, LVSI, depth of invasion)
| Stage | Surgical Procedure | What's Removed | Rationale |
|---|---|---|---|
| IA1 (no LVSI) | Cone biopsy (if fertility desired) or Simple (extrafascial) hysterectomy [14][15] | Cone: cone-shaped portion of cervix including TZ. Simple hysterectomy: uterus + cervix only (no parametrium, no vaginal cuff, no nodes) | Very very early (microscopic < 3mm deep) [15] — risk of LN metastasis < 1%, risk of parametrial involvement < 1% → radical surgery is unnecessary. Cone biopsy is sufficient if margins clear and no LVSI, allowing future fertility |
| IA1 (with LVSI) / IA2 | Cone + pelvic lymph node assessment (SLN biopsy or full lymphadenectomy) OR Modified radical hysterectomy (Type B) + pelvic lymphadenectomy | Uterus + cervix + medial parametrium + pelvic LN | LVSI increases LN metastasis risk to ~5–8%; IA2 has ~5% LN risk. Need to assess nodes. Modified radical approach removes limited parametrium |
| IB1 / IB2 / IIA1 | Wertheim's hysterectomy (radical hysterectomy + systematic pelvic lymphadenectomy) [14][15] | Uterus, upper vagina, parametria, and pelvic lymph nodes [15] | What makes a hysterectomy radical? → simple hysterectomy + removal of upper vagina, parametria and pelvic lymph nodes [14]. The parametrium must be removed because the risk of microscopic parametrial involvement is significant at this stage. Pelvic lymphadenectomy provides staging and therapeutic benefit |
| IB3 / IIA2 (bulky ≥ 4cm) | Radical hysterectomy possible but often followed by adjuvant CCRT → "double treatment" with increased morbidity. Many centres prefer primary CCRT for bulky tumours | — | Bulky tumours have higher rates of positive margins and LN metastasis at surgery → high likelihood of needing adjuvant radiotherapy anyway → better to avoid surgery + RT combination |
| Fertility-sparing surgery | Radical trachelectomy + pelvic lymphadenectomy ± cerclage | Removes cervix + parametrium but preserves the uterine body | For young women with Stage IA2–IB1 (≤ 2cm) who desire future fertility. The uterine body is preserved and a cerclage is placed to support future pregnancies. Must have negative nodes and negative margins. Pregnancy outcomes are reasonable but higher risk of preterm delivery |
Trans-abdominal route / open surgery [14]
It used to be via robot, so we are evolving backwards, WHY? → There was a very large multi-centred randomised trial comparing open route vs. laparoscopic / robotic route for hysterectomy — results showed laparoscopic / robotic surgery have worse outcomes [14]
This refers to the LACC Trial (Ramirez et al., NEJM 2018) — a landmark study that changed practice globally:
- Compared open radical hysterectomy vs. minimally invasive (laparoscopic/robotic) radical hysterectomy for early cervical cancer
- Found that minimally invasive surgery had worse disease-free survival (DFS) and worse overall survival (OS)
- The difference was striking and unexpected
Postulation is that after the uterus is removed, it has to be removed out of the small ports, so it will touch the abdominal cavity → along with high pressure gas in laparoscopic surgery, this will spread the tumour cells all over the abdomen (has not been proven yet) [14]
- Another theory: the use of a uterine manipulator during laparoscopy may push tumour cells into the peritoneal cavity or through the uterine vessels
- Current standard: open abdominal radical hysterectomy is the recommended route for cervical cancer
LACC Trial — Exam Favourite
If asked "why is open surgery preferred over laparoscopic/robotic for cervical cancer?", reference the LACC Trial: minimally invasive radical hysterectomy showed worse oncological outcomes (inferior DFS and OS). Possible explanations include tumour spillage during specimen extraction through small ports, CO2 pneumoperitoneum dispersing tumour cells, and uterine manipulator use.
| Complication | Mechanism |
|---|---|
| Ureteric injury / fistula | Ureter runs through the cardinal ligament ("water under the bridge") — at risk during parametrial dissection |
| Bladder dysfunction (neurogenic bladder) | Parasympathetic nerve fibres (S2–S4) to the bladder run through the cardinal and uterosacral ligaments — may be damaged during radical dissection → urinary retention, overflow incontinence |
| Lymphoedema (lower limbs) | Pelvic lymphadenectomy disrupts lymphatic drainage |
| Lymphocyst | Lymphatic fluid accumulates in the retroperitoneal space after lymphadenectomy |
| Haemorrhage | Injury to internal iliac vessels or branches |
| DVT / PE | Pelvic surgery + malignancy = high thrombotic risk |
| Sexual dysfunction | Vaginal shortening (upper vaginal cuff removed); nerve injury |
B2. Radiotherapy
Radiotherapy is the backbone of treatment for locally advanced cervical cancer (Stage IIB and beyond) and serves as an alternative to surgery for early disease if surgery is contraindicated.
Radiotherapy — for early disease if surgery not suitable; for late disease (Stage 2 or above) [13]
| Type | Description | Role in Cervical Cancer |
|---|---|---|
| External Beam Radiotherapy (EBRT) | High-energy X-rays delivered from outside the body to the pelvis (and para-aortic region if nodes involved). Typically 45–50.4 Gy in 25–28 fractions over 5–6 weeks | Treats the primary tumour, parametrium, pelvic sidewall, and regional lymph nodes. The "wide field" approach covering the entire pelvis |
| Brachytherapy ("brachy" = short/close) | Radioactive source placed directly inside the uterine cavity and vaginal fornices (intracavitary) or within the tumour itself (interstitial). Delivers very high dose to the tumour with rapid dose fall-off to spare adjacent normal tissues | Essential component — delivers the "boost" dose to the cervix/tumour. Without brachytherapy, local control rates are significantly inferior. The combination of EBRT + brachytherapy is standard |
The cervix is ideally suited for brachytherapy because:
- It is a hollow organ — you can insert applicators directly into the uterine canal and vaginal fornices
- The inverse square law means radiation dose drops off rapidly with distance — so the bladder and rectum (which are close by) receive relatively low doses compared to the tumour
- Studies consistently show that brachytherapy improves local control and overall survival compared to EBRT alone
| Indication | Details |
|---|---|
| Primary treatment for Stage IIB–IVA | CCRT (cisplatin + EBRT + brachytherapy) is standard |
| Alternative to surgery for Stage IB–IIA | If patient is medically unfit for surgery (comorbidities, advanced age), or declines surgery. Cure rates are equivalent to surgery for early-stage disease |
| Adjuvant after surgery | If high-risk features found on post-operative pathology (see below) |
| Palliative | Symptom control in Stage IVB (pain, bleeding, obstruction) |
| Acute (during / shortly after treatment) | Late (months to years later) | Mechanism |
|---|---|---|
| Radiation cystitis (frequency, dysuria, haematuria) | Radiation fibrosis of bladder → contracted bladder, chronic haematuria | Radiation damages rapidly dividing urothelium (acute) → then causes vascular damage and fibrosis (late) |
| Radiation proctitis (diarrhoea, tenesmus, rectal bleeding) | Radiation proctitis (chronic), rectal stricture, fistula | Same principle — rectal mucosa is radiosensitive |
| Radiation enteritis (nausea, diarrhoea) | Small bowel obstruction (adhesions, strictures) | Small bowel loops in the pelvis are irradiated |
| Skin erythema (perineum) | Skin fibrosis | Epithelial damage |
| Fatigue, bone marrow suppression | — | Pelvic bone marrow irradiated |
| Vaginal mucositis | Vaginal stenosis, dryness, dyspareunia | Vaginal epithelial damage → fibrosis. Patients advised to use vaginal dilators post-RT |
| — | Premature ovarian failure | Ovaries are exquisitely radiosensitive; even low doses cause permanent ovarian failure in young women |
| — | Secondary malignancy (rare) | Radiation-induced mutagenesis in surrounding normal tissues |
| — | Vesicovaginal / rectovaginal fistula | Radiation necrosis of tissue between organs |
Long-Term Morbidities of Radiotherapy
This is precisely why surgery is preferred for early disease — it avoids long-term morbidities of radiotherapy [14][15]. Radiation-induced complications (fibrosis, fistulae, stenosis, bowel obstruction, premature menopause) can be devastating and lifelong. For early-stage disease where surgery can be curative, avoiding radiation preserves quality of life.
B3. Chemotherapy
Chemotherapy — in combination with radiotherapy (chemo-irradiation) [13]
Chemotherapy in cervical cancer is used in three main contexts:
Sometimes have concept of chemo-irradiation → chemo acts as a radiation sensitiser (low chemo dose, much less side effects) [14]
| Aspect | Details |
|---|---|
| Regimen | Weekly cisplatin (40 mg/m²) given concurrently during EBRT |
| Mechanism | Cisplatin is a radiosensitiser — it enhances the cytotoxic effect of radiation by: (1) inhibiting DNA repair after radiation-induced damage, (2) generating free radicals that augment radiation-induced oxidative stress, (3) synchronising cells into the radiosensitive G2/M phase of the cell cycle |
| Dose | Much lower than systemic chemotherapy doses → "low chemo dose, much less side effects" compared to full-dose chemo |
| Evidence | Multiple landmark trials (GOG-120, Rose 1999) demonstrated that CCRT with cisplatin improves OS by ~30–50% compared to radiotherapy alone for locally advanced cervical cancer. This was a paradigm shift |
| Indication | Stage IIB–IVA (primary CCRT); adjuvant after surgery with high-risk features |
Recent update — INTERLACE Trial (2024): Addition of induction chemotherapy (carboplatin + paclitaxel × 6 cycles) before CCRT improves overall survival in locally advanced cervical cancer. This is evolving standard of care.
With systemic disease which has spread beyond the radiation field, will need further treatment via systemic treatment → chemotherapy, combined with targeted therapy (bevacizumab) [14]
| Regimen | Details |
|---|---|
| First-line | Cisplatin + paclitaxel (or carboplatin + paclitaxel if cisplatin not tolerated) + bevacizumab ± pembrolizumab |
| Second-line | Various options: topotecan, gemcitabine, vinorelbine; or immunotherapy (pembrolizumab if PD-L1+) |
- Historically used to shrink bulky tumours before surgery
- Current evidence does NOT support NACT followed by surgery as superior to primary CCRT
- Not standard of care; CCRT remains preferred for locally advanced disease
For recurrence — targeted therapy: Bevacizumab. Used in combination with chemo [13]
| Agent | Mechanism | Indication | Key Trial |
|---|---|---|---|
| Bevacizumab ("bev-a-CIZ-u-mab") | Monoclonal antibody against VEGF (Vascular Endothelial Growth Factor) → inhibits tumour angiogenesis → starves tumour of blood supply | Recurrent / metastatic cervical cancer, combined with cisplatin + paclitaxel | GOG-240: adding bevacizumab to chemotherapy improved OS from 13.3 to 17.0 months |
| Pembrolizumab | Anti-PD-1 immune checkpoint inhibitor → restores T-cell-mediated anti-tumour immunity | Recurrent/metastatic cervical cancer with PD-L1 positive tumours (CPS ≥ 1); now also in first-line with chemo + bevacizumab | KEYNOTE-826: adding pembrolizumab to chemo ± bevacizumab improved OS in PD-L1+ cervical cancer |
| Tisotumab vedotin | Antibody-drug conjugate targeting tissue factor (TF) expressed on cervical cancer cells; delivers cytotoxic payload directly to tumour cells | Second-line recurrent/metastatic cervical cancer | innovaTV 204: significant response rates in previously treated disease |
Evolving Landscape — Immunotherapy in Cervical Cancer
Pembrolizumab (anti-PD-1) is now part of first-line treatment for recurrent/metastatic cervical cancer (KEYNOTE-826). This makes PD-L1 testing (Combined Positive Score, CPS) an important part of the workup for advanced/recurrent disease.
HPV-associated cancers have high mutational burden and neoantigen load, making them good candidates for immune checkpoint inhibitors.
B5. Adjuvant Therapy After Surgery — When and Why
After radical hysterectomy, the post-operative pathology may reveal features that increase the risk of recurrence. The decision for adjuvant treatment is based on two categories of risk factors:
| Factor | Why It's High Risk |
|---|---|
| Positive lymph nodes | Indicates tumour has already spread beyond the cervix through lymphatics |
| Positive surgical margins | Residual tumour left behind → local recurrence |
| Parametrial involvement | Should not be found after surgery (would have been treated with CCRT primarily) but if present → local recurrence risk |
→ Adjuvant treatment: Concurrent cisplatin + pelvic EBRT (GOG-109/Intergroup 0107 trial)
These are combinations of factors that together confer increased risk:
| Factor | Why It Matters |
|---|---|
| LVSI | Lymphovascular space invasion = tumour cells in lymphatic/blood vessels = micrometastatic potential |
| Deep stromal invasion (outer 1/3 of cervix) | Deeper invasion = closer to parametrium and lymphatics |
| Large tumour size (> 4cm) | Larger tumour = higher recurrence rate |
→ The Sedlis criteria define combinations of these three factors that warrant adjuvant pelvic RT (GOG-92 trial) → Adding concurrent cisplatin to RT in intermediate-risk is increasingly practiced (extrapolated from high-risk data)
→ Observation and follow-up only. No adjuvant treatment needed.
| FIGO Stage | Primary Treatment | Notes |
|---|---|---|
| IA1 (no LVSI) | Cone biopsy (fertility desired, margins clear) OR Simple hysterectomy [15] | LN risk < 1% → no lymphadenectomy needed |
| IA1 (LVSI+) / IA2 | Cone + SLN / lymphadenectomy OR Modified radical hysterectomy + pelvic LN dissection | LVSI increases LN risk to ~5–8% |
| IB1 / IB2 | Radical hysterectomy (Wertheim's) + pelvic lymphadenectomy [15] OR Primary RT/CCRT if unfit for surgery | Surgery preferred (preserves ovarian function, avoids RT morbidity) |
| IB3 / IIA2 (bulky) | Primary CCRT (preferred) OR Radical hysterectomy + likely adjuvant CCRT | Beyond 4cm → cannot do surgery → will choose radiotherapy [14]; if surgery done, high probability of needing adjuvant RT → "double treatment" |
| IIB – IVA | Concurrent chemoradiotherapy (CCRT): weekly cisplatin + EBRT + brachytherapy [13][14] | Standard of care since late 1990s; cure rates ~50–65% for Stage IIB–III |
| IVB (distant mets) | Palliative systemic therapy: cisplatin/carboplatin + paclitaxel + bevacizumab ± pembrolizumab [13][14] | Goal: prolong survival, maintain quality of life. Palliative RT for symptom control (bleeding, pain) |
| Recurrence | Depends on prior treatment and site of recurrence: (1) Central pelvic recurrence after RT → pelvic exenteration (radical salvage surgery); (2) Distant recurrence → systemic chemo ± bevacizumab ± immunotherapy | Pelvic exenteration = removal of uterus + vagina + bladder and/or rectum — a morbid but potentially curative operation for isolated central recurrence |
D. Special Scenarios
| Stage | Option | Requirements |
|---|---|---|
| IA1 (no LVSI) | Cone biopsy alone | Clear margins, no LVSI, reliable follow-up |
| IA2 / IB1 (≤ 2cm) | Radical trachelectomy + pelvic lymphadenectomy | Tumour ≤ 2cm, no LVSI on imaging, negative nodes, squamous or usual-type adenocarcinoma, adequate cervical length remaining |
- Rare but devastating situation
- Management depends on gestational age and stage:
- Early stage + advanced gestation: may delay treatment until fetal viability (> 32–34 weeks) → caesarean delivery → then definitive treatment
- Advanced stage + early gestation: requires discussion about termination to allow definitive treatment
- Must involve multidisciplinary team (gynaecological oncologist, neonatologist, maternal-fetal medicine)
- Surgery may be contraindicated due to comorbidities
- Primary radiotherapy (EBRT + brachytherapy) achieves equivalent cure rates to surgery for early-stage disease
- Concurrent cisplatin may be omitted if renal function is poor or patient is too frail
Prognostic factors in cervical cancer [15]:
- Stage — the single most important prognostic factor
- Lymph node metastasis — most powerful predictor within a given stage
- Histology — adenocarcinoma and neuroendocrine types have worse prognosis than SCC stage-for-stage
Additional prognostic factors:
- Tumour size
- Depth of stromal invasion
- LVSI
- Surgical margins
- HPV status (HPV-independent tumours have worse prognosis)
- Response to treatment (rapid response to CCRT = better outcome)
| Stage | Approximate 5-Year Survival |
|---|---|
| IA | > 95% |
| IB | 80–90% |
| IIA | 70–80% |
| IIB | 60–70% |
| IIIA–IIIB | 30–50% |
| IIIC (node positive) | 40–60% |
| IVA | 15–25% |
| IVB | < 15% |
| Aspect | Protocol |
|---|---|
| Schedule | Every 3 months for first 2 years, every 6 months for years 3–5, then annually |
| Assessment | History (symptoms of recurrence: bleeding, pain, leg oedema), speculum exam, bimanual/rectovaginal exam, vault cytology |
| Tumour markers | SCC Ag (for SCC) — rising levels may indicate recurrence before clinical detection |
| Imaging | CT/PET-CT as indicated by symptoms or rising markers; not routine in asymptomatic patients (varies by centre) |
| Surveillance for RT complications | Renal function (ongoing hydronephrosis?), bladder/bowel symptoms, vaginal health, bone density (premature menopause) |
High Yield Summary — Management of Cervical Cancer
Core principle: Stage determines treatment.
Surgery (early disease — Stage I):
- IA1 no LVSI: cone biopsy or simple hysterectomy
- IA2 / IB1–IB2: Wertheim's radical hysterectomy + pelvic lymphadenectomy (open abdominal route — LACC trial)
- Advantages: preserves ovarian function, avoids RT morbidity
Radiotherapy (early if unfit; late = standard):
- EBRT + brachytherapy (brachytherapy is essential for adequate local control)
- Side effects: cystitis, proctitis, vaginal stenosis, premature menopause, fistulae
CCRT (Stage IIB–IVA):
- Weekly cisplatin + EBRT + brachytherapy — cisplatin is a radiosensitiser
- ~30–50% survival improvement over RT alone
Recurrent / Metastatic (Stage IVB):
- Cisplatin + paclitaxel + bevacizumab ± pembrolizumab
- Central pelvic recurrence after RT → pelvic exenteration
Adjuvant after surgery:
- High risk (positive nodes/margins/parametrium) → CCRT
- Intermediate risk (LVSI + deep invasion + large tumour) → Pelvic RT ± cisplatin
Prognostic factors: Stage > Lymph node status > Histology
Active Recall — Management of Cervical Cancer
References
[13] Lecture slides: GC 112. Abnormal vaginal bleeding Gynaecological cancer.pdf (p16, slides 31–32) [14] Lecture slides: Block C - Abnormal vaginal bleeding_ gynaecological cancer.pdf (p28–29) [15] Lecture slides: GC 112. Abnormal vaginal bleeding Gynaecological cancer.pdf (p17, slides 33–34)
Complications of Cervical Cancer
Complications of cervical cancer arise from three distinct sources: (1) the disease itself (local and distant), (2) the treatment, and (3) emergencies. Let's work through each systematically from first principles.
A. Complications of the Disease Itself
These complications stem from the pattern of cervical cancer spread. How does cervical cancer spread? → Local [3] is the primary route, but lymphatic and haematogenous spread also occur in advanced disease.
A1. Local Complications (Direct Tumour Extension)
The cervix sits at the crossroads of the pelvis — surrounded by the ureters, bladder, rectum, and major neurovascular structures. As the tumour grows, it invades these structures sequentially.
| Aspect | Detail |
|---|---|
| Mechanism | The ureter crosses under the uterine artery at the level of the cervix ("water under the bridge"). As cervical cancer invades laterally into the parametrium (cardinal ligament), it compresses or directly invades the ureter → ureteric obstruction → hydronephrosis → back-pressure on the kidney → obstructive nephropathy |
| Presentation | May be silent (no pain if gradual obstruction); loin pain if acute; rising creatinine on blood tests; oliguria/anuria if bilateral |
| Clinical significance | Bilateral ureteric obstruction → renal failure → Stage IIIB by FIGO. This is one of the most common causes of death in untreated cervical cancer. Must be detected early on RFT and imaging |
| Management | Percutaneous nephrostomy or ureteric stenting to relieve obstruction before definitive cancer treatment; nephrotoxic chemotherapy (cisplatin) cannot be given if renal function is impaired |
Renal Failure in Cervical Cancer — Life-Threatening
Obstructive renal failure is the single most common cause of death in untreated or end-stage cervical cancer. Always check RFT at presentation and during follow-up. A rising creatinine in a cervical cancer patient = ureteric obstruction until proven otherwise.
| Type | Mechanism | Presentation |
|---|---|---|
| Vesicovaginal fistula (VVF) | Tumour invades anteriorly through the vaginal wall into the bladder, or treatment (surgery/radiotherapy) causes tissue necrosis between the two structures → abnormal communication | Continuous urinary incontinence — urine constantly leaks from the vagina. Devastating for quality of life [16] |
| Rectovaginal fistula (RVF) | Tumour invades posteriorly through the rectovaginal septum into the rectum, or radiation necrosis creates the communication | Passage of faeces and flatus per vagina — profoundly distressing |
| Ureterovaginal fistula | Ureteric injury (from surgery or tumour invasion) → urine leaks into vagina | Continuous watery vaginal discharge (urine) |
| Vesicouterine / vesicocervical fistula | Less common; tumour erodes between cervix/uterus and bladder | Cyclic haematuria (Youssef syndrome if after caesarean — not relevant here); urinary incontinence |
Fistulae can result from either the tumour itself (Stage IVA) or as a complication of radiotherapy (radiation necrosis). This dual aetiology is important to distinguish because management differs.
| Structure | Mechanism | Presentation |
|---|---|---|
| Bladder | Direct anterior invasion through vesicovaginal septum | Haematuria, frequency, urgency, suprapubic pain; fistula (see above) |
| Rectum | Direct posterior invasion through rectovaginal septum | Rectal bleeding, tenesmus, mucoid rectal discharge, obstruction; fistula |
Confirmation requires cystoscopy or proctoscopy with biopsy — bullous oedema of the bladder mucosa alone is NOT sufficient to diagnose Stage IVA; you need histological confirmation of tumour cells in the bladder/rectal mucosa.
| Aspect | Detail |
|---|---|
| Mechanism | Tumour extends laterally through the parametrium to reach the bony pelvis (obturator internus, levator ani, pelvic sidewall) → Stage IIIB |
| Consequences | Compression of the internal iliac vessels → venous congestion and leg oedema [3]; compression/invasion of the sacral/lumbosacral nerve plexus → back pain [3], sciatica, neuropathic pain; compression of the obturator nerve → medial thigh pain and adductor weakness |
| "Frozen pelvis" | When bilateral parametria, pelvic sidewall, and surrounding structures are all infiltrated — uterus is completely immobile on examination. This represents locally advanced, inoperable disease |
| Aspect | Detail |
|---|---|
| Mechanism | Direct downward extension of cervical tumour along the vaginal wall |
| Presentation | Vaginal bleeding, palpable vaginal mass; if lower 1/3 vagina involved → Stage IIIA |
| Aspect | Detail |
|---|---|
| Mechanism | Tumour erodes into major pelvic vessels (uterine artery, internal iliac vessels) or the tumour surface has abnormal, friable neovasculature that bleeds heavily |
| Presentation | Acute, massive PV bleeding — can be life-threatening. More common in advanced/necrotic tumours |
| Management | Vaginal packing, tranexamic acid, blood transfusion, interventional radiology (uterine artery embolisation), palliative radiotherapy (haemostatic RT — often a single fraction of 8–10 Gy) |
| Aspect | Detail |
|---|---|
| Mechanism | Necrotic tumour is colonised by vaginal and bowel flora → ascending infection → pyometra (pus in uterus), pelvic abscess, or septicaemia. Obstructed ureter → infected hydronephrosis (pyonephrosis) → urosepsis |
| Presentation | Fever, foul-smelling discharge, pelvic pain, septic shock in severe cases |
Cervical cancer spreads via lymphatics in a predictable pattern: parametrial → obturator → internal iliac → external iliac → common iliac → para-aortic → mediastinal → supraclavicular (Virchow's node).
| Complication | Mechanism |
|---|---|
| Lower limb lymphoedema | Tumour-laden pelvic lymph nodes obstruct lymphatic drainage from the lower limbs → chronic swelling, skin changes, increased infection risk (cellulitis) |
| Lower limb DVT | Lymphadenopathy or tumour mass compresses the iliac veins → venous stasis → thrombosis (compounded by the hypercoagulable state of malignancy — Trousseau syndrome) |
| Pulmonary embolism | Consequence of DVT; also a significant cause of cancer-related death |
| Chylous ascites | Para-aortic nodal disease obstructs the cisterna chyli / thoracic duct → lymphatic fluid leaks into peritoneum (rare) |
Haematogenous spread occurs in advanced disease. The common sites and their complications:
| Site | Frequency | Complications | Presentation |
|---|---|---|---|
| Lung | Most common distant site | Pulmonary metastases (cannonball mets); pleural effusion; lymphangitis carcinomatosa [11] | Cough, haemoptysis, dyspnoea. Lymphangitis carcinomatosa from cervical cancer → severe and rapidly progressive SOB, marked hypoxaemia, CXR shows diffuse reticulonodular shadowing; CT shows polygonal thickened interlobular septa; prognosis very poor (majority dies ≤ 3–12 months) [11] |
| Liver | Second most common | Hepatomegaly, liver capsule pain, deranged LFT, jaundice | RUQ pain, hepatomegaly, elevated ALP/GGT, weight loss |
| Bone | Third most common | Bone pain, pathological fracture, hypercalcaemia, cord compression [16] | 4 complications of bony metastasis: bone pain, pathological fracture, malignant hypercalcaemia, neurological symptoms (cord compression) [16] |
| Brain | Rare in cervical cancer | Raised intracranial pressure, seizures, focal neurological deficits | Headache (worse in morning), nausea/vomiting, personality change, focal weakness [17] |
| Supraclavicular nodes | Left (Virchow's node) | Palpable nodal mass; indicates Stage IVB | Hard, non-tender, left supraclavicular lymphadenopathy |
B. Complications of Treatment
Every treatment modality carries its own complications. The art of cervical cancer management is balancing cure against treatment-related morbidity.
| Complication | Mechanism | Time Frame |
|---|---|---|
| Ureteric injury / Ureteric fistula | Ureter runs through the cardinal ligament ("water under the bridge") and is at risk during parametrial dissection in radical hysterectomy | Intraoperative / early post-op |
| Bladder dysfunction (neurogenic bladder) | Parasympathetic nerve fibres (S2–S4) supplying the detrusor muscle travel through the cardinal and uterosacral ligaments — radical excision of these ligaments damages these nerves → detrusor underactivity → urinary retention, overflow incontinence | Early post-op; may be permanent |
| Lower limb lymphoedema | Pelvic lymphadenectomy disrupts lymphatic drainage pathways from the lower limbs | Weeks to months post-op; chronic |
| Lymphocyst | Lymphatic fluid accumulates in the retroperitoneal space after lymphadenectomy → can compress ureter or iliac vessels → hydronephrosis or DVT | Weeks post-op |
| Haemorrhage | Injury to branches of the internal iliac artery/vein during pelvic dissection | Intraoperative |
| DVT / PE | Pelvic surgery + malignancy + immobility = high VTE risk (Virchow's triad) | Post-operative |
| Vaginal shortening / Sexual dysfunction | Upper vaginal cuff is removed in radical hysterectomy → shortened vagina → dyspareunia | Chronic |
| Wound complications | Infection, dehiscence (especially in the open abdominal approach) | Early post-op |
| Premature menopause | Only if ovaries are also removed (not routine in cervical cancer — ovaries are not removed since ovarian spread in usual type of HPV-associated cervical cancer is rare [14]). However, post-op radiotherapy will ablate ovarian function | If adjuvant RT given |
B2. Complications of Radiotherapy
Radiotherapy complications are categorised by timing:
| Complication | Mechanism |
|---|---|
| Radiation cystitis | Rapidly dividing urothelial cells are damaged by radiation → frequency, urgency, dysuria, haematuria |
| Radiation proctitis | Rectal mucosa is radiosensitive → diarrhoea, tenesmus, mucoid/bloody rectal discharge |
| Radiation enteritis | Small bowel loops within the pelvis are irradiated → nausea, vomiting, diarrhoea, abdominal cramps |
| Vaginal mucositis | Vaginal epithelium is directly irradiated → soreness, discharge, bleeding |
| Skin erythema (perineum) | Radiation dermatitis of the perineal skin |
| Fatigue / Bone marrow suppression | Pelvic bones contain haematopoietic marrow — irradiation causes myelosuppression → pancytopenia (especially during concurrent cisplatin) |
| Complication | Mechanism |
|---|---|
| Vaginal stenosis | Radiation fibrosis of the vagina → narrowing, shortening, dryness → severe dyspareunia and difficulty with follow-up vaginal exams. Prevention: vaginal dilator use + topical oestrogen post-RT |
| Radiation fibrosis of bladder | Chronic radiation damage to bladder vasculature → ischaemia → fibrosis → contracted, low-capacity bladder → frequency, chronic haematuria |
| Chronic radiation proctitis | Chronic mucosal damage → telangiectasia → rectal bleeding; stricture → obstruction |
| Small bowel obstruction | Radiation-induced adhesions and fibrosis of small bowel → mechanical obstruction. One of the most serious late complications |
| Vesicovaginal / Rectovaginal fistula | Radiation necrosis of tissues between organs → abnormal communication. May present months to years after treatment |
| Premature ovarian failure | Ovaries are exquisitely radiosensitive — even low-dose pelvic RT causes irreversible ovarian failure → surgical menopause in premenopausal women (hot flushes, vaginal atrophy, osteoporosis, cardiovascular risk). Option: ovarian transposition (oophoropexy — moving ovaries out of the radiation field) before RT if fertility/ovarian function preservation desired |
| Secondary malignancy | Radiation-induced mutagenesis in normal tissue within the field → risk of secondary cancers (bladder, rectal, vaginal cancers) many years later. Low risk but real (~1–2% over 20 years) |
| Pelvic insufficiency fractures | Radiation damages bone vasculature and osteoblasts → weakened sacrum and pelvic bones → stress fractures |
| Lymphoedema | Fibrosis of pelvic lymphatics from RT (compounded if lymphadenectomy also performed) |
Why Surgery Is Preferred for Early Disease — Revisited
Advantages of surgery: preserve ovarian function; avoids long-term morbidities of radiotherapy [14][15]. The chronic complications of pelvic radiotherapy — vaginal stenosis, bowel obstruction, fistulae, premature menopause, secondary malignancy — are lifelong burdens. For early-stage disease where surgery alone can be curative, avoiding these is a major advantage. This also explains why "double treatment" (surgery followed by adjuvant RT) is avoided when possible — it combines the morbidity of both modalities.
| Complication | Mechanism |
|---|---|
| Nephrotoxicity | Cisplatin is directly toxic to renal tubular epithelial cells → acute tubular necrosis, chronic renal impairment. Requires aggressive pre-hydration with IV normal saline. Particularly dangerous in cervical cancer patients who may already have obstructive nephropathy |
| Ototoxicity | Cisplatin damages cochlear hair cells → high-frequency sensorineural hearing loss (irreversible) |
| Neurotoxicity | Peripheral neuropathy (cumulative, dose-dependent) — tingling, numbness in hands and feet (stocking-glove distribution) |
| Nausea and vomiting | Cisplatin is one of the most emetogenic chemotherapy agents — stimulates CTZ and vagal afferents. Requires prophylactic antiemetics (5-HT3 antagonist + dexamethasone + NK1 receptor antagonist) |
| Myelosuppression | Damages rapidly dividing bone marrow progenitor cells → neutropenia (infection risk), anaemia, thrombocytopenia |
| Electrolyte disturbance | Renal magnesium wasting → hypomagnesaemia (cisplatin damages the ascending loop of Henle) |
| Agent | Key Complications | Mechanism |
|---|---|---|
| Bevacizumab | Hypertension, proteinuria, GI perforation, thromboembolism, wound healing impairment, haemorrhage (especially fistula-related in irradiated pelvis) | Anti-VEGF → impaired endothelial function, impaired wound healing, vessel fragility |
| Pembrolizumab | Immune-related adverse events (irAEs): pneumonitis, colitis, hepatitis, thyroiditis, hypophysitis, skin rash, nephritis | Anti-PD-1 → releases the "brakes" on T cells → autoimmune-like inflammation in normal tissues |
Several life-threatening emergencies can arise:
| Emergency | Mechanism | Management |
|---|---|---|
| Massive PV haemorrhage | Tumour erosion into major pelvic vessels or heavy bleeding from friable tumour surface | ABC resuscitation, vaginal packing, tranexamic acid, blood transfusion, urgent uterine artery embolisation or palliative haemostatic RT |
| Obstructive renal failure | Bilateral ureteric obstruction by tumour/nodes | Emergency percutaneous nephrostomy or ureteric stenting; correct hyperkalaemia if present |
| Urosepsis / Pyelonephritis | Obstructed, infected kidney (pyonephrosis) | IV broad-spectrum antibiotics + urgent drainage (nephrostomy) |
| Pulmonary embolism | DVT from pelvic venous compression + hypercoagulability of malignancy | Anticoagulation (LMWH preferred in cancer-associated VTE); CTPA for diagnosis |
| Spinal cord compression | Vertebral metastasis compresses spinal cord (usually thoracic) [16] | Dexamethasone 4mg IV Q6H if neurological symptoms present → surgical decompression + stabilisation if unstable, or RT alone if stable/unfavourable prognosis [16][17] |
| Malignant hypercalcaemia | Bone metastases → osteolytic activity → calcium release; or PTHrP secretion (rare in cervical cancer) | Aggressive IV hydration + IV bisphosphonate (zoledronic acid) ± calcitonin for rapid correction; denosumab if refractory or CKD [16] |
| DIC | Advanced metastatic disease → release of tissue factor and procoagulant substances → consumptive coagulopathy | Treat underlying cause (cancer treatment), supportive blood product replacement |
These are often overlooked but profoundly important:
| Complication | Context |
|---|---|
| Sexual dysfunction | Vaginal stenosis (from RT), vaginal shortening (from surgery), loss of libido (premature menopause, psychological impact), dyspareunia — affects intimate relationships |
| Premature menopause symptoms | Hot flushes, vaginal dryness, mood changes, osteoporosis, cardiovascular risk — especially devastating in young women treated with pelvic RT |
| Infertility | Hysterectomy or pelvic RT ablates fertility permanently (unless fertility-sparing surgery was possible) |
| Body image and self-esteem | Stoma (after pelvic exenteration), lymphoedema, fistula, vaginal changes |
| Psychological distress | Depression, anxiety, PTSD — particularly related to cervical cancer's association with HPV/sexual transmission; feelings of stigma or guilt |
| Social isolation | Fistula (continuous leakage of urine/faeces), malodorous discharge — profoundly isolating |
| Financial burden | Treatment costs, inability to work, need for ongoing supportive care |
Cervical cancer — asymptomatic at early stage — need screening. If treated early, has good prognosis [18]
Treatment of early invasive cervical cancer → 5-year survival rate is good for early cancers, around 85% [19]
| Stage | 5-Year Survival | Key Prognostic Factors |
|---|---|---|
| IA | > 95% | Almost always curable |
| IB | 80–90% | Tumour size, LVSI, depth of invasion |
| IIA | 70–80% | Nodal status becomes increasingly important |
| IIB | 60–70% | Parametrial involvement; response to CCRT |
| IIIA–IIIB | 30–50% | Hydronephrosis (renal failure), pelvic sidewall fixation |
| IIIC (node positive) | 40–60% | Number of positive nodes, para-aortic involvement |
| IVA | 15–25% | Bladder/rectal invasion |
| IVB | < 15% | Distant metastases — median survival 8–13 months |
High Yield Summary — Complications of Cervical Cancer
Disease complications (by mechanism):
- Ureteric obstruction → hydronephrosis → renal failure (most common cause of death; "water under the bridge")
- Fistulae: VVF (continuous urinary incontinence), RVF (faeces per vagina) — from tumour or RT
- Pelvic sidewall disease: leg oedema (venous/lymphatic compression), back pain (nerve plexus invasion)
- Haemorrhage: tumour erosion into vessels — emergency
- Lymphangitis carcinomatosa of lungs: severe SOB, poor prognosis
Treatment complications:
- Surgery: ureteric injury, neurogenic bladder, lymphoedema, DVT
- Radiotherapy: acute (cystitis, proctitis, enteritis); chronic (vaginal stenosis, fistula, bowel obstruction, premature menopause, secondary malignancy)
- Cisplatin: nephrotoxicity, ototoxicity, neuropathy, emetogenicity
- Bevacizumab: hypertension, GI perforation, fistula risk in irradiated pelvis
Emergencies: massive haemorrhage, obstructive renal failure, urosepsis, PE, cord compression, hypercalcaemia
Core message: If treated early, good prognosis (85% 5-year survival for early disease). Screening is key.
Active Recall — Complications of Cervical Cancer
References
[3] Lecture slides: GC 112. Abnormal vaginal bleeding Gynaecological cancer.pdf (p11, slide 22; p13, slide 26) [11] Senior notes: Ryan Ho Respiratory.pdf (p151) [14] Lecture slides: Block C - Abnormal vaginal bleeding_ gynaecological cancer.pdf (p29) [15] Lecture slides: GC 112. Abnormal vaginal bleeding Gynaecological cancer.pdf (p17, slide 33) [16] Senior notes: Maksim Medicine Notes.pdf (p45, p47, p55) [17] Senior notes: Ryan Ho Neurology.pdf (p164, p170) [18] Lecture slides: GC 112. Abnormal vaginal bleeding Gynaecological cancer.pdf (p23, slide 45) [19] Lecture slides: Block C - Abnormal cervical smear_ cervical cancer; cancer screening.pdf (p76)
High Yield Summary
Definition: Malignant neoplasm of the cervix, arising at the transformation zone (SCJ). > 99% HPV-driven.
Epidemiology: 4th most common female cancer globally; median age 55 in HK; declining with screening + vaccination. Bimodal peak 35–39 and 60–64 years.
HPV is NECESSARY but NOT SUFFICIENT — ~90% clear within 2 years; persistent high-risk HPV → CIN → invasive CA over 10–20 years.
Risk factors — two buckets:
- HPV acquisition: Early sex, multiple partners, OCP use
- Impaired clearance: Smoking, immunosuppression (HIV), lower socioeconomic class
Molecular pathophysiology: E6 degrades p53 (loss of apoptosis) + E7 inactivates pRb (uncontrolled proliferation). HPV DNA integration → constitutive E6/E7 overexpression.
Histology: SCC ~70–75% (HPV 16 most common) | Adenocarcinoma ~20–25% (rising; HPV 18/45; harder to detect on smear) | Others rare.
HK note: HPV 52 and 58 prevalent — Gardasil 9 covers these.
Pre-invasive: CIN 1/2/3 → AIS. Invasive = basement membrane breached.
FIGO 2018 staging watershed: Stage IIB (parametrial invasion) = surgery vs CCRT divide.
Clinical: Early often asymptomatic. PCB is hallmark. Late: back pain, leg oedema, hydronephrosis, fistulae.
Vaccination works after sexual debut — protects new cells; body sheds infected cells over time.
High Yield Summary — Differential Diagnosis
Approach: Anatomical — vagina → cervix → endometrium → ovaries. Separate benign vs malignant.
Most important benign mimics of PCB: Cervical ectropion (most common), cervical polyp, cervicitis.
| Feature | Cervical CA | Ectropion | Polyp | Endometrial CA |
|---|---|---|---|---|
| Bleeding | PCB, IMB | Light PCB | IMB, PCB | PMB (not PCB) |
| Speculum | Irregular, friable, necrotic | Smooth red area | Pedunculated, smooth | Cervix normal; blood from os |
| Age | Median 55 | Young, on OCP | Any | Postmenopausal |
| Diagnosis | Biopsy | Clinical + smear | Polypectomy + histology | Endometrial biopsy |
Always exclude pregnancy (β-hCG) in reproductive-age women.
Key rule: Visible suspicious cervical lesion → BIOPSY directly — Pap smear is screening only, can miss invasive CA.
Endometrial CA (most common gynae malignancy in HK): Normal cervix, PMB, obesity/DM/tamoxifen RFs.
Tumour markers: SCC antigen for SCC (monitoring only, NOT diagnostic). CA-125 only if adenocarcinoma confirmed on histology.
Imaging for DDx/staging: MRI pelvis best for local spread.
High Yield Summary — Diagnosis
Diagnosis is ALWAYS histological — no blood test or imaging diagnoses cervical cancer.
Two pathways:
- Symptomatic (PCB, visible lesion) → direct punch biopsy
- Screening (abnormal smear/HPV+) → colposcopy + directed biopsy
| Modality | Role | System |
|---|---|---|
| Cytology (Pap smear) | Screening | Bethesda (NILM, ASC-US, LSIL, HSIL, SCC, AGC) |
| Histopathology (biopsy) | Diagnosis | WHO (CIN, AIS, invasive CA) |
Colposcopy: Acetic acid → acetowhite; Lugol's → unstained = abnormal. Atypical vessels/ulceration = invasive cancer.
Punch biopsy confirms cancer; cone/LLETZ needed to measure invasion depth (Stage IA1 ≤ 3mm; IA2 3–5mm).
Staging workup (after histological confirmation):
| Test | Purpose |
|---|---|
| CBP, RFT, LFT | Anaemia; RFT critical (ureteric obstruction → hydronephrosis → Stage IIIB) |
| SCC Ag (or CA-125 if adeno) | Baseline monitoring — NOT diagnostic |
| MRI pelvis + abdomen | Best modality — parametrial invasion = disrupted dark stromal ring on T2W |
| CXR ± CT | Lung mets |
| PET-CT/MRI | Nodal + distant staging (Stage IIIC) |
| EUA | Parametrial/pelvic sidewall assessment |
| Cystoscopy/proctoscopy | Stage IVA (biopsy-proven mucosal invasion) |
2018 FIGO: Now incorporates imaging/pathology (especially Stage IIIC nodal disease).
High Yield Summary — Management
Stage determines treatment. Watershed: Stage IIB = primary CCRT, not surgery.
| Stage | Treatment |
|---|---|
| IA1 (no LVSI) | Cone biopsy (fertility) or simple hysterectomy |
| IA1 (LVSI+) / IA2 | Cone + SLN or modified radical hysterectomy + LN |
| IB1 / IB2 / IIA1 | Wertheim's radical hysterectomy + pelvic lymphadenectomy (open abdominal — LACC trial) |
| IB3 / IIA2 (bulky ≥ 4cm) | Primary CCRT preferred (avoid surgery + adjuvant RT "double treatment") |
| IIB – IVA | CCRT: weekly cisplatin + EBRT + brachytherapy |
| IVB | Palliative chemo (cisplatin + paclitaxel + bevacizumab ± pembrolizumab) |
Surgery advantages: Preserves ovarian function (ovaries not removed — ovarian spread rare in HPV-associated SCC); avoids RT long-term morbidity.
CCRT: Cisplatin is a radiosensitiser (low dose, few side effects). ~30–50% OS improvement over RT alone.
Adjuvant after surgery:
- High risk (positive nodes/margins/parametrium) → CCRT
- Intermediate risk (LVSI + deep invasion + large tumour — Sedlis criteria) → pelvic RT ± cisplatin
Fertility-sparing: Radical trachelectomy for IA2–IB1 ≤ 2cm, negative nodes.
Recurrence: Central after RT → pelvic exenteration. Distant → chemo + bevacizumab ± immunotherapy.
Prognostic factors: Stage > lymph node status > histology (adenocarcinoma/neuroendocrine worse).
High Yield Summary — Complications
Disease complications (local spread):
- Ureteric obstruction → hydronephrosis → renal failure — most common cause of death ("water under the bridge")
- Fistulae: VVF (continuous urinary incontinence), RVF (faeces per vagina) — tumour or RT
- Pelvic sidewall: Leg oedema (venous/lymphatic compression), back pain (nerve plexus)
- Haemorrhage: Tumour erosion into vessels — emergency
- Lymphangitis carcinomatosa of lungs: severe SOB, poor prognosis (majority die ≤ 3–12 months)
Distant mets: Lung (most common), liver, bone (pain, fracture, hypercalcaemia, cord compression), brain (rare).
Treatment complications:
- Surgery: Ureteric injury, neurogenic bladder, lymphoedema, DVT
- Radiotherapy: Acute (cystitis, proctitis, enteritis); chronic (vaginal stenosis, fistula, bowel obstruction, premature menopause, secondary malignancy)
- Cisplatin: Nephrotoxicity (dangerous with obstructive uropathy), ototoxicity, neuropathy
- Bevacizumab: GI perforation, fistula risk in irradiated pelvis
Emergencies: Massive PV haemorrhage, obstructive renal failure, urosepsis, PE, cord compression.
Core message: Screening is key — if treated early, ~85% 5-year survival. Asymptomatic at early stage.
Approach To Pelvic Mass
A systematic clinical evaluation of an abnormal mass in the pelvis using history, physical examination, imaging, and laboratory studies to determine its origin (gynecologic, gastrointestinal, or urologic), nature (benign versus malignant), and appropriate management.
Ovarian Cancer
Ovarian cancer is a malignant neoplasm arising from the ovary or fallopian tube, with epithelial ovarian cancer accounting for most adult cases.