Cervical Cancer Screening and Prevention

Slide 1 · Cervical Cancer

Screening and Prevention

Precursor biology • Cytology • HPV-based screening

Colposcopy • Prevention

Dr Abu Suraih Sakhri

MBBS, MD (Pathology)

www.abusuraihsakhri.com

Slide 2 · Learning objectives

Explain why the natural history of HPV-associated cervical neoplasia makes screening effective.

Interpret the biological meaning of Pap cytology, high-risk HPV tests, and colposcopic biopsy.

Connect LSIL and HSIL findings to appropriate surveillance or treatment concepts.

Distinguish screening recommendations from risk-based management and primary prevention.

Slide 3 · Three linked opportunities for prevention

Prevent HPV acquisition

Detect persistent hrHPV or precursor

Triage & confirm lesions

Treat significant precursor

Vaccination and effective screening are complementary, not interchangeable.

Slide 4 · The biological window that makes screening possible

HPV acquisition

Persistent oncogenic infection

Squamous precursor lesion

Potential invasive cancer

Progression generally unfolds over years; Surveillance can interrupt the pathway before invasion.

Slide 5 · Screening targets a preinvasive disease phase

Cytologic abnormalities can be detected because precursor lesions exfoliate cells.

Histologic progression can remain confined to the epithelium before stromal invasion.

Precursor detection enables treatment before an invasive mass or symptoms develop.

An HPV-positive result identifies infection/risk, not a diagnosis of cancer.

Slide 6 · Transformation zone: The sampling target

Ectocervical squamous lining

Squamocolumnar junction

Transformation zone

Endocervical canal

Adequate sampling depends on obtaining representative cells from the relevant cervical epithelium.

Slide 7 · Why the transformation zone matters

Squamous metaplasia develops at the squamocolumnar junction.

The transformation zone is the characteristic site of HPV-associated cervical SIL.

Cytology specimens are collected with brushes or spatulas designed to sample this region.

The location and visibility of the transformation zone vary across individuals.

Slide 8 · HPV-associated carcinogenesis: Causal sequence

High-risk HPV persistence

Viral oncoprotein effects

Dysregulated cell cycle

Increasing epithelial atypia

Persistent transforming infection—not merely transient HPV detection—underlies precursor risk.

Slide 9 · Productive infection versus transforming infection

LSIL: Productive infection

Viral replication is prominent.

Koilocytic atypia reflects viral cytopathic change.

Squamous maturation is partly preserved.

Most lesions regress rather than progress.

HSIL: Transforming infection

Cell-cycle deregulation predominates.

Proliferation extends above the basal layer.

Maturation is reduced or arrested.

Substantial precursor risk warrants close evaluation.

Slide 10 · Terminology across classification systems

Older terms

CIN system

Two-tier terminology

Mild dysplasia

CIN 1

LSIL

Moderate dysplasia

CIN 2

HSIL

Severe dysplasia / carcinoma in situ

CIN 3

HSIL

Slide 11 · Normal cervical squamous maturation

Basement membrane

Mature squamous cells occupy the superficial layers; Proliferation is concentrated basally.

Original schematic — not a histology image

Slide 12 · LSIL: Limited atypia with retained maturation

Basement membrane

Low-grade alteration predominates in basal and parabasal regions; Koilocytosis is evident in maturing cells.

Original schematic — not a histology image

Slide 13 · HSIL: Expansion of immature atypical cells

Basement membrane

Atypical immature cells extend upward; Marked loss of maturation reflects increased proliferative activity.

Original schematic — not a histology image

Slide 14 · Morphologic basis of a squamous intraepithelial lesion

Nuclei become enlarged, hyperchromatic, irregular, and variable in size or shape.

Increasing histologic grade corresponds to reduced epithelial maturation.

Perinuclear halos with nuclear atypia are characteristic of koilocytic change.

The basement membrane remains intact in an intraepithelial lesion.

Slide 15 · Koilocytosis links morphology to HPV infection

Koilocytes show a perinuclear cytoplasmic halo with an atypical enlarged nucleus.

This cytopathic pattern is especially prominent in productive HPV infection.

A clear halo alone is insufficient without accompanying nuclear atypia.

Koilocytic changes support LSIL but are not a substitute for the complete morphologic assessment.

Slide 16 · Why HSIL cells differ from normal surface cells

High-risk HPV-driven cycle deregulation expands immature epithelial populations.

Less terminal differentiation produces exfoliated cells with scant cytoplasm.

Nuclear enlargement raises the nucleus-to-cytoplasm ratio.

Pap cytology uses these changes to identify high-grade precancer risk.

Slide 17 · Screening and diagnostic confirmation are different

Population screening test

Abnormal result / risk stratification

Colposcopy ± biopsy

Histologic diagnosis

A screening result triggers further assessment; Biopsy establishes tissue architecture when indicated.

Slide 18 · How a conventional Pap smear is produced

Expose cervix

Rotate brush / spatula

Transfer cells to slide

Fix & Papanicolaou stain

Microscopic assessment

The method assesses exfoliated cells, not full epithelial thickness.

Slide 19 · Conventional and liquid-based cervical cytology

Conventional cytology spreads the collected cells directly on a glass slide.

Liquid-based cytology places collected material into a preservative for processing.

Both approaches are assessed for cellular abnormalities and specimen adequacy.

Sample quality and appropriate cervical sampling affect clinical performance.

Slide 20 · Specimen adequacy is a preanalytic safeguard

Identification, sampling, fixation, and transport influence result reliability.

Excess obscuring blood, inflammation, or scant cellularity may limit interpretation.

The cytology report should identify unsatisfactory material rather than imply normality.

Follow-up after an unsatisfactory result differs from follow-up after a valid negative result.

Slide 21 · Pap cytology: Progressive nuclear dominance

Superficial normal

LSIL / koilocyte

HSIL

Higher nuclear-to-cytoplasmic ratio correlates with impaired squamous differentiation.

Schematic cell silhouettes — not source cytology

Slide 22 · Normal superficial squamous cells on a Pap test

A mature cell has abundant, often polygonal cytoplasm.

Its nucleus is comparatively small and compact.

Organized maturation produces a low nucleus-to-cytoplasm ratio.

These features provide a comparator for dysplastic cells.

Slide 23 · LSIL cytology: Koilocytes and mild nuclear atypia

Typical koilocytes show a perinuclear halo and a thickened cytoplasmic rim.

Nuclei are enlarged and may be irregular or hyperchromatic.

Cytoplasm often remains more abundant than in HSIL.

Cytologic LSIL indicates a low-grade epithelial abnormality, not invasive carcinoma.

Slide 24 · HSIL cytology: Immature high-N:C cells

Cells frequently have less cytoplasm and more conspicuous nuclear atypia.

Irregular nuclear contours and coarse chromatin support a high-grade interpretation.

These abnormalities reflect dysregulated epithelial proliferation.

HSIL cytology requires risk-appropriate evaluation; It is not automatically proof of invasion.

Slide 25 · Cytology and histology answer different questions

Pap cytology

Examines exfoliated individual cells.

Recognizes atypia and cytomorphologic grade.

Cannot directly show epithelial thickness or stromal invasion.

Cervical biopsy

Preserves epithelial architecture.

Estimates the depth of immature atypical cells.

Assesses the basement membrane and stromal invasion.

Slide 26 · Limits of morphology-only screening

Abnormal cells may be missed because lesions were not sampled or shed sparsely.

Reactive or inflammatory changes can complicate cytologic interpretation.

A negative Pap result does not exclude all clinically significant disease.

A positive result requires management guided by risk and relevant history.

Slide 27 · High-risk HPV testing changes the screening question

Collect sample

Molecular HPV assay

Detect oncogenic HPV nucleic acid

Estimate subsequent CIN3+ risk

HPV testing identifies etiologic risk upstream of overt cytologic dysplasia.

Slide 28 · What a high-risk HPV result actually means

A positive assay detects one or more carcinogenic HPV types covered by that test.

It does not establish the duration of infection or the presence of HSIL.

Most HPV infections clear; Persistent high-risk infection is the concern.

Interpretation depends on HPV genotype, cytology, prior screening, and clinical context.

Slide 29 · Why HPV tests can be more sensitive than cytology

Viral DNA may be detected before exfoliated dysplastic cells appear.

Testing is less dependent on an observer identifying cell morphology.

Greater sensitivity can also detect transient, clinically nonprogressive infections.

Thus specificity for prevalent high-grade lesions is often lower than Pap cytology.

Slide 30 · Pap cytology compared with hrHPV DNA testing

Dimension

Cytology

High-risk HPV test

Primary target

Morphologic atypia

Oncogenic infection

Typical strength

Morphologic specificity

Higher sensitivity for precancer

Common limitation

Sampling/reader dependence

Transient infections reduce specificity

Clinical meaning

Abnormal cells identified

Higher future precursor risk

Slide 31 · Why patient age affects HPV test specificity

Transient HPV detection is common after sexual debut.

Testing a population with frequent transient infection increases false-positive referrals for significant precancer.

Age and local guideline frameworks therefore influence screening strategy.

Do not generalize a single age threshold across ACS, USPSTF, and WHO policies.

Slide 32 · Cotesting: Complementary observations

Cervical sample

Cytologic evaluation + hrHPV assay

Joint risk information

Surveillance or diagnostic action

Cotesting is one accepted screening option, but is not interchangeable with management of an abnormal result.

Slide 33 · Screening eligibility is defined before test selection

Routine population screening applies to asymptomatic persons with a cervix at average risk.

Abnormal bleeding, a visible lesion, or other symptoms require diagnostic assessment—not routine screening alone.

Prior CIN2+, treatment, immunosuppression, and other factors can change surveillance.

Screening policies must be applied within the named health system.

Slide 34 · Contemporary screening recommendations are not uniform

Organization / scope

Starting age

Preferred strategy

ACS (US; 2025 update)

25 years

Clinician-collected primary HPV every 5 years

WHO (general population; 2021)

30 years

HPV DNA every 5–10 years

WHO (women with HIV; 2021)

25 years

HPV DNA every 3–5 years

Slide 35 · ACS: Routine screening begins at age 25

The ACS guideline applies to asymptomatic individuals with a cervix at average risk.

Routine screening begins at age 25 and generally continues through age 65.

The preferred screening method is primary hrHPV testing on a clinician-collected cervical specimen.

A prior abnormal result or relevant clinical risk can require a separate management pathway.

Slide 36 · ACS: Clinician-collected primary HPV testing

The provider samples the cervix during a speculum examination.

A negative result permits a five-year screening interval at average risk.

A positive specimen can support additional triage testing from collected cervical material.

Test intervals assume validated assays and appropriate follow-up systems.

Slide 37 · ACS 2025: Self-collected HPV specimens are an option

Self-collected vaginal specimens may be used with approved tests and devices.

The clinician-collected cervical specimen remains the preferred approach.

After a negative self-collected HPV result, repeat screening in three years.

A positive self-collected result requires clinician evaluation and cervical sampling.

Slide 38 · Self-collection versus clinician collection

Self-collected vaginal sample

Potentially improves access and autonomy.

HPV testing only, using validated device/assay.

ACS negative-result interval: 3 years.

Positive results require clinical follow-up.

Provider-collected cervical sample

Directly targets cervical epithelial cells.

Allows reflex or additional cervical tests.

ACS preferred primary HPV strategy.

ACS negative-result interval: 5 years.

Slide 39 · ACS: Alternative screening modalities

Clinician-collected HPV/Pap cotesting every five years remains acceptable.

Pap cytology alone every three years is an alternative when HPV strategies are unavailable.

Choice of pathway does not remove the need for proper abnormal-result follow-up.

Do not apply average-risk intervals to those requiring surveillance after precancer.

Slide 40 · ACS 2025: Prerequisites for screening exit

Average-risk patients may stop at age 65 when adequate recent negative screening is documented.

Examples: Last two provider-collected HPV tests or cotests normal, or last three Pap tests normal.

A history of CIN2+ within the preceding 25 years precludes routine exit.

Unknown screening history generally calls for continued screening until exit criteria are met.

Slide 41 · Who does not follow the average-risk algorithm?

Previous cervical precancer or cancer may require prolonged surveillance.

Immunosuppressed individuals, including those living with HIV, need tailored regimens.

Prenatal diethylstilbestrol exposure is another higher-risk circumstance.

Symptomatic patients require diagnostic work-up independent of their screening interval.

Slide 42 · WHO: Primary HPV testing supports elimination programmes

WHO 2021 suggests primary HPV DNA testing beginning at age 30 in the general population.

A regular five- to ten-year interval can be used in screen-and-treat or triage pathways.

National programme design depends on access, capacity, treatment linkage, and quality assurance.

The goal is a functioning screening-to-treatment system, not HPV testing in isolation.

Slide 43 · WHO: Women living with HIV need a distinct strategy

WHO 2021 suggests beginning HPV DNA-based screening at age 25.

Regular three- to five-year screening is advised in a screen–triage–treat approach.

Higher vulnerability to persistent HPV infection justifies differentiated prevention.

Programme recommendations should not be substituted for individual specialist management.

Slide 44 · An abnormal screening result initiates triage

HPV/Pap abnormality

Review prior tests & genotype

Estimate CIN3+ risk

Surveillance / colposcopy / treatment

The next action is determined by risk, not simply whether a test was “positive.”

Slide 45 · What colposcopy contributes after abnormal screening

A magnified cervical examination seeks abnormal epithelial regions.

Dilute acetic acid can accentuate an abnormal surface as an acetowhite area.

The examination directs targeted biopsy of suspicious tissue.

Colposcopy findings require histologic correlation when biopsy is indicated.

Slide 46 · Colposcopic biopsy: Sampling-to-diagnosis

Visualize cervix

Apply acetic acid

Identify suspicious zone

Take targeted biopsy

Assess histology

Acetowhite appearance is a localization clue—not an independently definitive diagnosis.

Slide 47 · Why colposcopy is not the same as biopsy

Visual patterns can suggest lesion distribution and severity.

They do not demonstrate the epithelial full-thickness or stromal interface microscopically.

Biopsy distinguishes LSIL from HSIL and assesses possible invasion.

Sampling error remains possible if the most relevant region is missed.

Slide 48 · Histologic LSIL usually favours conservative care

LSIL as a productive infection with high spontaneous regression.

A biopsy diagnosis must be interpreted with the cytology/HPV and screening history.

Observation is often appropriate when risk and reliable follow-up permit.

Ablation may be considered in selected settings, but is not a blanket default for all LSIL.

Slide 49 · Histologic HSIL is a clinically meaningful precursor

CIN2/CIN3 changes show more extensive atypia and less maturation.

HSIL is associated with appreciably greater progression risk than LSIL.

The pathology finding may require excisional or otherwise guideline-directed treatment.

Age, pregnancy, reproductive considerations, and confidence in follow-up influence choices.

Slide 50 · ASCCP: A risk-based approach replaces simple result rules

The 2019 ASCCP framework uses current HPV/cytology plus prior screening and clinical history.

Management thresholds are based on estimated immediate and five-year CIN3+ risk.

The same mild abnormality may be followed or referred depending on prior negative HPV-based screening.

Later ASCCP updates should be checked for applicable scenarios.

Slide 51 · ASCCP risk thresholds: Principal branch

Estimate immediate CIN3+ risk

≥4% → colposcopic evaluation

<4% → assess 5-year risk

Set surveillance interval

The 4% referral threshold is specific to the ASCCP risk framework, not an isolated test-result rule.

Slide 52 · High-risk genotype can change colposcopy decisions

HPV16 and HPV18 carry higher oncogenic risk than many other detected types.

ASCCP recommends colposcopy for HPV16- or HPV18-positive results even with NILM cytology.

A positive high-risk HPV test without genotype information is not managed identically in all contexts.

HPV results need cytologic and historical interpretation.

Slide 53 · Risk-based surveillance is not routine rescreening

After abnormal tests or treatment, return intervals are calculated from CIN3+ risk and prior findings.

One-year surveillance may be appropriate for selected minor abnormalities below the colposcopy threshold.

Post-treatment HSIL surveillance can extend long beyond initial excision.

Do not insert an average-risk five-year interval without establishing eligibility.

Slide 54 · Excision and ablation have different pathology implications

Excision removes tissue that can be evaluated for lesion extent and margin status.

Ablation destroys tissue and yields no intact specimen for microscopic review.

Conization or loop excision may be required for suitable high-grade lesions.

Choice requires histologic, colposcopic, and patient-specific assessment.

Slide 55 · Why preventing overtreatment matters

Many low-grade lesions regress without intervention.

Unnecessary excision exposes patients to procedural and reproductive harms.

Conversely, under-recognizing HSIL delays prevention of invasive disease.

Risk-based triage aims to balance sensitivity, referral burden, and harm.

Slide 56 · HPV vaccination provides primary prevention

Prophylactic vaccine

Type-specific immune response

Reduced new vaccine-type infections

Lower downstream HPV-associated precancer risk

Prophylactic vaccination prevents infection; It is not a treatment for existing CIN or persistent HPV.

Slide 57 · Nine-valent HPV vaccine: Included types

Oncogenic targets: HPV 16, 18, 31, 33, 45, 52, and 58.

Non-oncogenic wart-associated targets: HPV 6 and 11.

Coverage does not include every carcinogenic HPV genotype.

Consequently vaccination is not a reason to stop recommended cervical screening.

Slide 58 · CDC HPV vaccination: Initiation age determines series

Clinical group

Recommended series

Key qualification

Routine, age 11–12 (may start at 9)

2 doses if begun before 15

Second dose 6–12 months later

Initiated at age 15–26

3 doses

0, 1–2 and 6 months

Immunocompromised, age 9–26

3 doses

Regardless of age at initiation

Unvaccinated age 27–45

Shared decision-making

Not routine catch-up for all

Slide 59 · Why vaccination is recommended for all genders

Transmission of HPV involves sexual networks of all genders.

Vaccination can reduce infections that cause cervical cancer.

It also addresses other HPV-associated anogenital and oropharyngeal cancers.

Pre-exposure immunization provides the greatest preventive benefit.

Slide 60 · Aged 27–45 years: Shared clinical decision-making

CDC does not recommend universal catch-up vaccination beyond age 26.

Some previously unvaccinated adults aged 27–45 may benefit.

Prior HPV exposure reduces expected population-level benefit.

Decisions consider future exposure risk and patient preferences.

Slide 61 · Vaccinated people still require cervical screening

Vaccination does not treat an infection already acquired.

Not every oncogenic HPV type is included in the vaccine.

Individual vaccine histories and timing vary.

Current ACS screening recommendations still apply to vaccinated average-risk patients.

Slide 62 · Two preventive strategies protect at different points

Primary prevention

Vaccinate before HPV exposure.

Reduce acquisition of vaccine-targeted types.

Offer population-wide prevention for all genders.

Secondary prevention

Detect persistent hrHPV or abnormal cytology.

Confirm and treat relevant precancer.

Maintain repeat testing and follow-up systems.

Slide 63 · Population impact depends on screening completion

A screening test alone cannot prevent cancer if a positive result is never evaluated.

Barriers include access, cost, acceptability, recall, and pathology capacity.

Self-collection may remove some barriers but cannot substitute for needed cervical follow-up.

Organized programmes require tracking of results, referrals, and treatment completion.

Slide 64 · Why under-screened populations carry more disease burden

Absent or limited cytology programmes with continued cervical cancer mortality.

Cancer prevention requires early identification and management of precancer.

Screening participation and follow-up inequities can undermine test efficacy.

Improving programme continuity is as important as selecting a sensitive assay.

Slide 65 · Case 1: Asymptomatic 26-year-old, average risk

A 26-year-old with a cervix has no symptoms, no history of cervical precancer, and asks which U.S. Screening method is preferred.

Reasoning

Identify the guideline framework: ACS average-risk screening begins at age 25.

Choose clinician-collected primary HPV as the preferred ACS strategy.

If negative, the ACS interval is five years.

Apply ACS recommendations; Other organizations may use different age thresholds.

Slide 66 · Case 2: HPV-positive result with negative cytology

A 33-year-old has a positive high-risk HPV test and NILM cytology; HPV genotype and prior testing are not yet available.

Reasoning

A positive HPV assay is not a cancer diagnosis.

Genotype and prior HPV-based testing alter immediate CIN3+ risk.

Complete risk stratification before assigning colposcopy or surveillance.

Avoid the outdated rule that every HPV-positive/NILM result automatically receives a fixed cytology interval.

Slide 67 · Case 3: Biopsy reports LSIL / CIN1

A patient has biopsy-confirmed cervical LSIL and reliable access to repeat testing; No separate high-grade features are stated.

Reasoning

LSIL is typically associated with productive HPV infection.

Most lesions regress; Initial conservative management is often suitable.

Use current screening history and risk to specify follow-up.

Do not automatically equate LSIL biopsy with an indication for cone excision.

Slide 68 · Case 4: HSIL cytology and suspicious lesion

A 37-year-old has HSIL cytology and a visually suspicious cervical region at colposcopy.

Reasoning

Cytology raises concern but does not show stromal invasion.

Obtain indicated tissue for histologic assessment and manage per risk.

Biopsy/excision is needed to establish epithelial grade and exclude invasion.

Invasive carcinoma cannot be diagnosed from cytology alone.

Slide 69 · Case 5: Vaccinated individual asks to stop screening

A vaccinated 31-year-old with a cervix has normal previous testing and assumes vaccination removes screening needs.

Reasoning

Prophylactic vaccine protection is type-specific and not therapeutic.

Average-risk ACS screening continues irrespective of HPV vaccination.

Use an age-appropriate approved screening strategy.

Vaccination and screening work together rather than replace each other.

Slide 70 · Integrating screening and pathology in practice

Precursor lesions are detectable because cervical carcinogenesis generally has a prolonged preinvasive phase.

Pap cytology identifies cellular atypia; HPV assays identify etiologic risk; Biopsy defines tissue architecture.

Current management is history- and risk-dependent: A positive screen is not a treatment decision.

Vaccination and reliable screening–follow-up systems remain complementary.

Slide 71 · Five diagnostic and preventive distinctions to retain

Screening is for asymptomatic populations; Suspicious symptoms require diagnostic assessment.

HPV positive ≠ HSIL; HSIL cytology ≠ invasive carcinoma.

LSIL and HSIL have different natural histories and management implications.

High-risk genotype and prior test history may change management after an abnormal result.

Vaccinated individuals continue guideline-based screening.

Slide 72 · Primary textbook and contemporary guideline references

Robbins, Cotran & Kumar. Pathologic Basis of Disease. 11th ed. 2026. Chapter 22, pp. 906–910.

American Cancer Society. Cervical Cancer Screening Guideline (2020; updated Dec 2025).

Perkins RB et al. ASCCP Risk-Based Management Consensus Guidelines (2019; updates through 2023).

CDC. HPV Vaccine Recommendations (guidance accessed Oct 2026).

WHO. Guideline for Screening and Treatment of Cervical Pre-cancer Lesions. 2nd ed. 2021.