GC120 Abnormal Cervical Smear Cervical Cancer and Cancer Screening

An integrated approach to cervical screening, abnormal cytology, HPV testing, colposcopy, CIN treatment, post-treatment surveillance and HPV vaccination, based on the two updated GC120 lecture decks.

Abnormal Cervical Smear, Cervical Cancer & Cancer Screening

This GC120 lecture is split across two complementary updated decks:

  • Pathology and laboratory perspective: what cervical cytology reports mean, how cytology relates to biopsy, and how liquid-based cytology, HPV tests, automation and biomarkers are used.
  • Clinical and public-health perspective: who to screen, how to obtain a good sample, how to investigate an abnormal result, how CIN is treated, and how HPV vaccination prevents disease.

The unifying pathway is:

Persistent high-risk HPV infection → cervical precancer → invasion

Most HPV infections clear and many low-grade lesions regress. Screening therefore aims to find clinically important precancer, not merely every transient HPV infection [1,2].

Screening is not diagnosis

Screening is for an asymptomatic, apparently healthy population. Postcoital bleeding, unexplained intermenstrual bleeding, persistent abnormal discharge, pelvic pain, or a visible cervical lesion requires a diagnostic examination and timely biopsy/colposcopy pathway, even if a previous screen was negative. Do not use a screening smear to delay biopsy of an obvious tumour.


Cervical cancer satisfies the classic Wilson–Jungner principles:

RequirementWhy the cervix fits
Important health problemCervical cancer remains the fourth most common cancer in women worldwide; most deaths occur where vaccination, screening and treatment access are limited [3].
Recognisable latent stagePersistent oncogenic HPV usually precedes a long precancerous phase.
Accessible target organThe transformation zone can be sampled through a speculum examination.
Acceptable testCytology and clinically validated high-risk HPV assays can identify women needing surveillance or colposcopy.
Effective early treatmentTreating histological HSIL prevents progression while usually preserving the uterus.
Organised follow-upA register, recall system, laboratory quality assurance and colposcopy access convert a test into an effective programme.

The lecture's historical graphs show cervical-cancer incidence and mortality falling as Pap screening expanded. Interpret this as a population association supported by extensive programme evidence, not as proof that an individual negative smear permanently excludes cancer.

WHO elimination targets

The 90–70–90 strategy aims for, by 2030:

  • 90% of girls fully vaccinated against HPV by age 15;
  • 70% of women screened with a high-performance test by ages 35 and 45; and
  • 90% of women with cervical disease receiving appropriate treatment [3].

2. Cervical Anatomy, Transformation Zone & Sampling

The ectocervix is lined mainly by mature squamous epithelium; the endocervical canal is lined by glandular epithelium. Their meeting point is the squamocolumnar junction (SCJ). As the cervix matures and remodels, exposed columnar epithelium undergoes squamous metaplasia; the area between the original and current SCJ is the transformation zone (TZ).

The TZ matters because this metaplastic interface is where most HPV-associated squamous precancers arise. A brush must sample the ectocervix and the endocervical/TZ component appropriate to the cervix being examined.

The slides show the practical sequence:

  1. Confirm identity, indication, previous results and relevant history; label the vial/request correctly.
  2. Position the speculum and fully expose the cervix under good light.
  3. Inspect before sampling. A friable, ulcerated, irregular or exophytic lesion goes to urgent diagnostic assessment/biopsy.
  4. Place the cervical broom centrally so its longer fibres enter the os and its shorter fibres contact the ectocervix.
  5. Rotate and transfer the entire cellular sample into the preservative vial according to the device manufacturer's instructions; the slide's exact turn/rinsing counts are device-specific, not universal rules.

Liquid-based cytology (LBC) disperses the sample into a standardised thin area. Compared with a conventional smear, it reduces obscuring blood/mucus and permits reflex HPV or other validated tests from the residual sample. It does not rescue a poorly positioned brush or a missed lesion.

Common causes in the slide images are:

  • too few squamous cells;
  • air-drying or thick-spread artefact in a conventional smear;
  • heavy blood or neutrophilic inflammation obscuring epithelial cells;
  • treatment effect or severe atrophy that prevents reliable interpretation; and
  • specimen/identity or processing problems.

Repeat an unsatisfactory test according to the reported reason and local pathway. Treat a genuine symptomatic infection when indicated; do not give antibiotics solely to make a smear readable. A short course of vaginal oestrogen may help selected postmenopausal patients with marked atrophy after contraindications and preferences are considered, but it is not an automatic response to every unsatisfactory sample.


3. Cytology, Histology & Terminology

Cytology samples exfoliated cells and is reported using The Bethesda System. Histology examines tissue architecture from biopsy/excision and uses WHO terminology. Cytology predicts risk; histology determines whether abnormal cells are confined above the basement membrane and how much epithelium is involved.

Cytology termMeaningVisual clue in the decksWhat it does not mean
ASC-USAtypical squamous cells of undetermined significanceMild nuclear enlargement/irregularity that exceeds reactive change but is insufficient for LSILNot cancer; it is a risk-stratification category.
ASC-HAtypical squamous cells, cannot exclude HSILSmall crowded cells with high nuclear-to-cytoplasmic ratio, but too scant/equivocal for definite HSILA negative HPV result does not make the cytological concern disappear; colposcopy is generally required.
LSILLow-grade squamous intraepithelial lesionKoilocytic change: perinuclear halo, enlarged irregular hyperchromatic nuclei, sometimes binucleationDoes not map perfectly to biopsy, though it commonly corresponds to HPV effect/CIN1.
HSILHigh-grade squamous intraepithelial lesionSmaller immature cells, high N:C ratio, coarse chromatin, irregular nuclear membranes and crowded groupsCytology cannot alone prove stromal invasion.
Squamous carcinomaCytology suspicious/diagnostic of malignant squamous cellsMarked pleomorphism, abnormal keratinisation and tumour diathesis may be presentTissue diagnosis and staging are still required.

The lecture diagram should be read from left to right:

  • LSIL/CIN1: atypical proliferating cells are mainly confined to the lower third; maturation persists above.
  • HSIL/CIN2: atypia and disordered maturation extend roughly into the lower two-thirds.
  • HSIL/CIN3: near-full-thickness atypia with little surface maturation.
  • Microinvasion/invasion: atypical cells breach the basement membrane and enter stroma; this is a histological, not merely cytological, diagnosis.

Modern pathology commonly uses a two-tier LSIL/HSIL framework, with p16 immunohistochemistry used in selected equivocal lesions—not as a substitute for morphology.

Bethesda glandular abnormalities include:

  • atypical endocervical, endometrial or glandular cells;
  • atypical glandular/endocervical cells, favour neoplasia;
  • endocervical adenocarcinoma in situ (AIS); and
  • adenocarcinoma.

The lecture's cytology–biopsy pairs illustrate two key lessons:

  1. Cytological atypia can reflect a benign mimic, such as microglandular hyperplasia.
  2. True AIS may coexist with squamous HSIL and can extend discontinuously up the endocervical canal, making a satisfactory excisional specimen important.

AGC can signal cervical, endometrial or occasionally extrauterine pathology. It therefore cannot be managed as “just another mildly abnormal smear.”


4. HPV Biology & Modern Screening Tests

The slide pathway contains reversible and irreversible-looking arrows for a reason:

Normal cervix ⇄ HPV infection ⇄ precancer → invasive cancer
                   clearance       regression
  • Acquisition of HPV is common.
  • Persistence of a carcinogenic HPV type is the crucial risk state.
  • HPV16 and HPV18 confer particularly high risk, but validated assays test a broader high-risk panel.
  • HPV testing detects infection/risk earlier than cytology detects abnormal cells; its greater sensitivity comes with lower specificity in younger populations where transient infection is common.

  • Cytology: detects abnormal cervical cells.
  • Primary high-risk HPV testing: detects carcinogenic HPV DNA or mRNA; a positive result requires triage, not automatic treatment.
  • Co-testing: HPV plus cytology from a clinician-collected cervical sample.
  • Visual inspection with acetic acid (VIA): a resource-dependent population approach, not interchangeable with formal colposcopy.
  • Biomarker triage: validated p16/Ki-67 dual stain or other locally approved strategies may increase specificity among HPV-positive patients.

Only a clinically validated assay used for its approved specimen and purpose should guide management. Research genotyping platforms, methylation assays, microRNA and HPV E6/E7 tests shown in the deck are not all routine screening tests.

The imaging-system diagram is a workflow rather than an autonomous diagnosis:

sample collection → LBC preparation → automated slide scanning/field selection → trained human review and sign-out

Automation can prioritise suspicious fields in the “needle-in-a-haystack” search, but laboratory accreditation, quality controls, validated performance and expert review remain essential.

The 2026 HKCOG addendum accepts a validated self-collected vaginal sample for HPV testing as an alternative, while preferring clinician-collected cervical specimens [5]. Important limits:

  • vaginal self-samples are for HPV testing, not cervical cytology;
  • reflex cytology or p16/Ki-67 cannot be performed on a vaginal self-sample because it lacks a direct cervical-cell sample;
  • HPV16/18 positivity leads to colposcopy; other high-risk HPV positivity requires a clinician-collected cervical specimen for triage; and
  • two inadequate/inconclusive results should lead to clinician collection.

5. Who to Screen in Hong Kong

These recommendations apply to asymptomatic, average-risk women and should not be imported into post-treatment, immunocompromised or diagnostic pathways [4,6].

GroupCurrent Hong Kong recommendation
Age 25–29, ever sexually activeCytology. After two consecutive normal annual tests, screen every 3 years.
Age 30–64, ever sexually activeCytology as above, or primary HPV testing every 5 years, or co-testing every 5 years. DH services have used primary HPV testing for this age group since April 2023.
Age 65+May stop if routine screening over the preceding 10 years was normal and there is no relevant high-grade history; screen if never screened.
Age 21–24No routine average-risk screening; individual assessment if increased risk.
Previous histological HSIL/CIN2+Long surveillance pathway; do not stop merely because age 65 is reached.
Immunocompromised/HIV, DES exposure or other high riskSpecialist/risk-specific schedule.

Vaccination, menopause, sterilisation, absence of family history, current abstinence or no symptoms do not by themselves remove the need for screening when the person meets programme criteria.

Routine screening is often deferred because pregnancy-related cervical change and contact bleeding can complicate sampling, but a never-screened patient may be offered screening after individual assessment. An abnormal result is not ignored: high-grade cytology is evaluated in pregnancy to exclude invasion, while endocervical curettage is contraindicated and treatment of precancer is usually deferred postpartum [6].

The public-health slides contrast:

  • opportunistic screening: testing only when someone happens to attend care; and
  • organised screening: defined target population, consented registry, invitations/recall, standardised reporting, laboratory and colposcopy quality assurance, documented referral and active follow-up of abnormal results.

The Hong Kong data in the deck are programme statistics, not the prevalence of abnormality in all local women. They also show the central challenge: those least likely to attend may carry the greatest preventable risk.


6. What to Do with an Abnormal Screening Result

Management depends on the current test, HPV genotype, age, pregnancy/immunosuppression, prior results, prior treatment and estimated CIN3+ risk. Avoid memorising an abnormal word in isolation.

  1. Is there a symptom or visible lesion? Use a diagnostic cancer pathway, not routine screening recall.
  2. Was the sample satisfactory? If not, repeat/resolve the adequacy problem promptly.
  3. Is the result high-grade or glandular? ASC-H, HSIL, AGC, AIS or suspected carcinoma generally needs colposcopic/diagnostic assessment.
  4. If HPV-positive, what genotype and triage result? HPV16/18 carries higher risk; other types usually undergo reflex cytology/validated triage.
  5. What is the history? A minimally abnormal result after previous negative HPV testing may carry a different risk from the same result after treatment or persistent positivity.

ResultCore action (simplified; follow local algorithm)
ASC-USHPV triage/co-test is preferred when available. High-risk HPV positivity generally leads to colposcopy; HPV negativity permits surveillance/return according to the applicable local pathway.
LSILColposcopy or risk-based surveillance depends on age, HPV and prior results; do not ablate based on cytology alone.
ASC-HColposcopy irrespective of a reassuring HPV result; endocervical sampling when the examination is not fully visualised and it is safe.
HSILPrompt colposcopy with biopsy; selected very-high-risk, non-pregnant adults may be offered expedited excision after counselling.
AGC/AISColposcopy plus endocervical assessment; endometrial sampling when indicated. AGC-favour neoplasia/AIS generally requires a diagnostic excision if initial assessment does not explain the cells.
Suspected carcinoma/visible growthUrgent biopsy and cancer staging pathway.

Do not mix algorithms

The lecture presents the 2024 HKCOG algorithms. ASCCP and other jurisdictions increasingly express management using immediate and 5-year CIN3+ risk thresholds. Their logic is compatible—equal risk receives equal action—but individual intervals are not safely interchangeable across programmes [6,7].


Colposcopy magnifies the cervix after saline inspection and application of 3–5% acetic acid; Lugol iodine may be added. It is a target-selection examination, not histology.

Image sequence in the deck

  1. Before solution: identify the os, SCJ/TZ, inflammation, polyps, ulceration and any gross tumour.
  2. After acetic acid: dysplastic epithelium becomes acetowhite. Dense, rapidly appearing, persistent opacity; coarse punctation/mosaic; sharp borders; ridge/inner-border signs; and atypical vessels increase concern.
  3. After Lugol iodine: glycogen-rich mature squamous epithelium stains dark brown. Immature metaplasia, atrophy, inflammation and dysplasia may be iodine-negative (mustard/yellow), so iodine negativity is sensitive but nonspecific.
  4. Biopsy: target the most abnormal area—especially dense acetowhite change or atypical vasculature—not simply the easiest site.

A fully adequate assessment documents whether the SCJ and upper limit of every lesion are visible. The modern description is TZ type 1, 2 or 3 rather than merely calling the examination “satisfactory/unsatisfactory.” A type 3 TZ does not automatically mandate excision; cytology, HPV risk, age, endocervical assessment and suspicion of invasion determine the next step.


8. Histological CIN: Observation, Ablation & Excision

Most CIN1 represents productive HPV infection and regresses. Observation with HPV-based testing/co-testing is preferred. Treatment may be considered for a large/persistent lesion or when reliable follow-up cannot be achieved, but only after the cervix has been adequately assessed and invasion excluded [6].

  • CIN3: treatment is recommended outside exceptional circumstances.
  • CIN2: treatment is usual, but carefully selected patients prioritising future pregnancy may undergo specialist observation when the SCJ is visible, endocervical sampling is reassuring and adherence is reliable.
  • Excision is generally preferred when invasion, glandular disease, a type 3 TZ or cytology–histology discordance is a concern because it provides a specimen.
  • Ablation destroys tissue and is suitable only when eligibility criteria are met and invasion/glandular disease are not suspected.

Cryotherapy: the probe must fully cover an eligible ectocervical lesion; the expanding white ice ball should extend beyond the lesion. Because no specimen remains, it is inappropriate when the lesion extends into the canal, is too large, the TZ is not fully seen, or cancer/glandular disease is possible.

LLETZ/LEEP sequence shown in the slides:

  1. delineate the TZ/lesion;
  2. pass an electrified wire loop through the transformation zone, ideally producing an intact, orientable specimen;
  3. retrieve the specimen for histology and margin assessment; and
  4. secure haemostasis, commonly with ball diathermy and/or haemostatic solution.

Cone biopsy: removes a deeper cone including endocervical canal. It is useful for AIS, suspected microinvasion, discordant high-grade results or disease extending beyond colposcopic view. The wider/deeper excision shown in the diagram is not “better” by default: excision depth should balance oncological adequacy against bleeding, stenosis and later preterm-birth risk.

HPV persistence predicts residual/recurrent CIN2+ better than margin status alone. Under HKCOG 2024, HPV testing or co-testing is performed at 6 months and then annually until two consecutive normal results, followed by 3-yearly HPV-based surveillance for 25 years, continuing beyond age 65 when necessary [6].

Complications to counsel about include bleeding, infection, cervical stenosis and an excision-depth-related increase in adverse obstetric outcomes. Hysterectomy is not first-line treatment for cytological HSIL or uncomplicated CIN alone.


The vaccines contain non-infectious virus-like particles; they prevent new infection but do not eradicate an existing HPV infection or treat established CIN.

VaccineTypes represented
Bivalent16, 18
Quadrivalent6, 11, 16, 18
Nonavalent6, 11, 16, 18, 31, 33, 45, 52, 58

Hong Kong's school programme provides 9-valent HPV vaccine to eligible Primary 5 girls and the second dose in Primary 6 [8]. Local eligibility/catch-up arrangements can change, so consult the current CHP programme rather than applying the deck's age table to every patient.

WHO permits a one- or two-dose schedule for many immunocompetent 9–20-year-olds as a public-health option, whereas Hong Kong's routine childhood programme remains a two-dose schedule. Immunocompromised people need at least two and, where possible, three doses. Vaccination is deferred during pregnancy; inadvertent administration is not an indication for pregnancy termination. There is no routine booster recommendation [8,9].

Vaccination is most effective before sexual exposure but prior sexual activity is not proof that every vaccine type has already been acquired. Vaccinated people still enter the recommended screening programme because vaccination does not cover every oncogenic HPV type and does not treat pre-existing disease.


  • Abnormal smear ≠ cervical cancer. It is a risk signal requiring the correct next step.
  • HPV-positive ≠ precancer. Persistence, genotype and triage determine risk.
  • Negative screen ≠ diagnostic clearance for bleeding or a visible lesion.
  • Cytology ≠ histology. LSIL/HSIL words exist in both systems but the sampled material and clinical meaning differ.
  • Colposcopy ≠ biopsy. Acetowhite and iodine-negative changes are not pathognomonic.
  • ASC-H/HSIL/AGC/AIS are not “repeat next year” results unless a specific post-colposcopy surveillance algorithm says so.
  • CIN1 usually regresses; CIN3 is treated. CIN2 sits between and may be observed only in carefully selected patients.
  • Ablation leaves no tissue. Never ablate when the TZ/lesion is not fully assessed or invasion/glandular disease is possible.
  • HPV vaccine is prophylactic, not therapeutic, and does not remove the need for screening.
  • Organised coverage and follow-up matter more than overscreening the same low-risk attendees.

  1. Cervical cancer is screenable because persistent high-risk HPV usually produces a long, detectable, treatable precancerous phase.
  2. Sample the transformation zone correctly and inspect the cervix before sampling; biopsy an obvious suspicious lesion.
  3. Bethesda cytology stratifies risk: ASC-US/LSIL are usually low risk; ASC-H/HSIL and glandular abnormalities require prompt assessment.
  4. HPV testing is more sensitive but needs genotype/cytology/biomarker triage to restore specificity.
  5. In Hong Kong, routine screening begins at 25 for those ever sexually active; primary HPV testing or co-testing is an option from age 30.
  6. Colposcopy uses acetic acid and sometimes Lugol iodine to locate biopsy targets; appearance alone is not diagnosis.
  7. CIN1 is usually observed; histological HSIL is treated or, for selected CIN2, closely observed. Excision provides tissue and must balance future obstetric risk.
  8. Long HPV-based surveillance is required after CIN2+ treatment.
  9. Nonavalent vaccination is primary prevention; it neither clears existing HPV nor replaces screening.

  1. Why is persistent HPV infection more clinically important than a single positive HPV test?
  2. What anatomical area must a cervical screening sample include, and why?
  3. How do the cytological appearances of LSIL and HSIL differ?
  4. Why does AGC trigger investigation beyond the cervix?
  5. What does dense acetowhite epithelium with coarse mosaic/punctation suggest, and what confirms the diagnosis?
  6. When is ablation unsafe compared with excision?
  7. What is the current routine Hong Kong screening schedule for ages 25–29 and 30–64?
  8. What additional step is needed after a non-16/18 high-risk HPV-positive vaginal self-sample?
  9. Why is prolonged surveillance needed after apparently successful CIN2+ treatment?
  10. Why must vaccinated patients still attend cervical screening?

[1] Lecture slides: GC120, Abnormal cervical smear—cervical cancer; cancer screening (Prof Annie Cheung), updated 26 August 2025, 41 slides. [2] Lecture slides: GC120, Abnormal cervical smear—cervical cancer; cancer screening (Prof SF Ngu), updated 26 August 2025, 60 slides. [3] World Health Organization — Global strategy to accelerate the elimination of cervical cancer (https://www.who.int/publications/i/item/9789240014107) [4] Hong Kong Cervical Screening Programme — Screening targets and recommendations (https://www.cervicalscreening.gov.hk/en/recommendations.html) [5] HKCOG — 2026 addendum: self-collected vaginal samples for HPV testing (https://www.hkcog.org.hk/hkcog/Download/Addendum_to_Guidelines_for_Cervical_Cancer_Prevention_and_Screening_January_2024.pdf) [6] HKCOG — Guidelines for Cervical Cancer Prevention and Screening, revised January 2024 (https://www.hkcog.org.hk/hkcog/Download/Revised_January_2024.pdf) [7] ASCCP — 2019 risk-based management guidelines, updates through 2023 (https://pmc.ncbi.nlm.nih.gov/articles/PMC10755815/) [8] Centre for Health Protection — Hong Kong HPV vaccination programme (https://www.chp.gov.hk/en/features/102146.html) [9] World Health Organization — HPV vaccine position paper, December 2022 (https://www.who.int/publications/i/item/who-wer9750-645-672/)

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