Clinical overview
Cervical cancer is the second commonest cancer in South African women and the leading cause of cancer death among them. This is not a problem of biology alone but of access: cervical cancer is almost entirely preventable, the natural history is slow (a decade or more from infection to invasion), and we possess effective tools to interrupt that history at three separate points — vaccination, screening, and treatment of pre-invasive disease. The reason South Africa still loses so many women is that those tools are unevenly delivered. Layered on top is the highest HIV burden of any country: HIV-driven immunosuppression accelerates HPV persistence, multiplies the risk of high-grade lesions, and shortens the runway from CIN to cancer. A registrar who understands screening must therefore hold two things together — the international evidence on which test, how often, in whom — and the specific South African policy that governs what actually happens in a Pretoria clinic or a rural Eastern Cape primary-care site.
The objective asks you to "consider" both the tests themselves and the SA policy. That means knowing the performance characteristics of cytology, HPV-DNA testing and visual inspection; understanding the screen–triage–treat logic; and being able to recite, defend and critique the National Department of Health (NDoH) screening policy and the SASOG/BetterGyn 2024 guideline that is steering South Africa towards HPV-based primary screening. This chapter frames screening as a population programme, not a clinic test, and connects it to hpv-pathology, cervical-carcinogenesis and cin-management.
Core knowledge
Why screening works: the natural history it exploits
Persistent infection with a high-risk human papillomavirus (HPV) — chiefly types 16 and 18, which cause roughly 70% of cervical cancers — is necessary for almost all cervical squamous and most glandular carcinomas. The viral oncoproteins E6 and E7 inactivate p53 and Rb respectively, driving the squamocolumnar junction through progressive intraepithelial change. In WHO 2020 (LAST-aligned) pathology terminology, transient productive infection produces a low-grade squamous intraepithelial lesion (LSIL, ≈ CIN 1), which usually regresses, whereas transforming infection produces a high-grade squamous intraepithelial lesion (HSIL, ≈ CIN 2–3), the true cancer precursor. Because progression from HSIL to invasion typically takes years, there is a long, detectable, treatable pre-invasive window — this is the entire rationale for screening. The screen identifies women carrying the virus or harbouring HSIL so that the lesion is ablated or excised before it becomes cancer.
The three screening tests
Figure D5.1 — The three screening tests compared: cytology vs HPV-DNA vs VIA (sensitivity, specificity, setting and self-sampling).
1. Cervical cytology (the Pap smear). A sample of the transformation zone is examined for dyskaryosis, reported using the Bethesda system (ASC-US, LSIL, ASC-H, HSIL, AGC). Its great strength is specificity and a long track record; its weakness is moderate, single-test sensitivity for HSIL (around 50–70%), which is why it must be repeated at intervals to be effective. It is operator- and laboratory-dependent and requires a functioning cytopathology service — in South Africa, the National Health Laboratory Service (NHLS).
2. High-risk HPV-DNA testing. A molecular assay detecting the DNA of oncogenic HPV types, often with partial genotyping that separately flags HPV 16 and 18. Its sensitivity for HSIL+ is high (>90%) and its negative predictive value is excellent, which is what allows long screening intervals and confident reassurance after a negative result. Its trade-off is lower specificity — many positives reflect transient infection that will clear — so a positive HPV test must be triaged (by genotyping, reflex cytology, or visual inspection) rather than taken straight to treatment. HPV testing can be done on a clinician-taken or self-collected vaginal sample, a feature with profound implications for reach in a country where pelvic examination is a major access barrier.
3. Visual inspection with acetic acid (VIA). The cervix is painted with dilute acetic acid; aceto-white areas suggest dysplasia. It is cheap, requires no laboratory, and gives an immediate result, enabling same-visit "screen-and-treat" with thermal ablation. Its sensitivity and specificity are operator-dependent and modest, and it performs poorly when the squamocolumnar junction is not fully visible (post-menopausal women). It remains valuable as a triage step or in resource-constrained, single-visit settings.
The modern paradigm: screen → triage → treat
Figure D5.2 — The screen → triage → treat paradigm: HPV-DNA primary screen, triage (genotyping/cytology/VIA), then thermal ablation or LLETZ.
The WHO and SASOG/BetterGyn 2024 logic is a sequence: a high-performance primary screen (HPV-DNA) identifies at-risk women; a triage test (HPV 16/18 genotyping, cytology, p16/Ki-67 dual-stain cytology, or VIA) selects those needing immediate intervention — note that dual-stain (p16/Ki-67) is now a WHO- and ASCCP-endorsed triage option (WHO screen-and-treat 2nd ed, 2024; ASCCP Enduring Guidelines, 2024), more specific than reflex cytology so it reduces over-referral, including in women living with HIV; and treatment is either ablative (thermal ablation, the modern replacement for cryotherapy) for eligible HSIL where the lesion and its margins are fully visible, or excisional (LLETZ — large loop excision of the transformation zone) where excision and histology are required (see cin-management). This replaces the older "screen with cytology, refer all abnormals to colposcopy" pathway and is what underpins WHO's elimination strategy.
The South African policy
Figure D5.3 — South African screening policy: the historic cytology programme shifting to HPV-primary screen–triage–treat (SASOG/BetterGyn 2024, DiaVACCS), with the intensified HIV schedule.
South Africa's public-sector cervical screening policy historically rested on cytology: offer asymptomatic HIV-negative women three free smears, starting at age 30, repeated every 10 years (i.e. at 30, 40 and 50). This conservative interval was a rationing decision driven by laboratory capacity, not by ideal biology, and it has long been criticised as under-screening. The critical exception is HIV: HIV-positive women are screened at the time of HIV diagnosis and then more frequently — approximately every three years — regardless of age, because immunosuppression so markedly increases HSIL incidence and progression risk. Cervical cancer is an AIDS-defining condition, and many South African women present with HIV and cervical disease simultaneously.
The SASOG/BetterGyn 2024 guideline, developed in collaboration with the NDoH, is steering the country towards HPV-DNA primary screening, informed by the locally-conducted DiaVACCS trial which compared screening strategies in a high-HIV-prevalence South African population. The direction of travel is: HPV test as the primary screen, triage of HPV-positive women (genotyping/cytology/VIA), and treat by thermal ablation or LLETZ — moving from a cytology-rationed programme towards the WHO-endorsed model. Because the exact intervals and age bands are being revised as the policy transitions, you should lead with the principle (HPV-based screen–triage–treat, with intensified screening in HIV) and confirm specific intervals against the current BetterGyn 2024 PDF and the NDoH policy before quoting hard numbers in an exam answer.
Primary prevention: HPV vaccination
Figure D5.4 — WHO's 90-70-90 elimination targets and HPV vaccination (9-valent, single-dose, SA school programme) as primary prevention.
Screening is secondary prevention; vaccination is primary. South Africa has run a school-based HPV vaccination programme since 2014, offering the vaccine to girls aged 9–14 (Grade 5+), and the programme is extending towards private schools and a single-dose schedule. The nonavalent (9-valent) vaccine offers the broadest protection. WHO endorsed a single-dose HPV schedule in 2022, and African immunisation advisory bodies (SAGE/RITAG, November 2023) supported its adoption — a major simplification for programme delivery. Vaccination and screening are complementary: a vaccinated cohort still needs screening (the vaccine does not cover every oncogenic type and uptake is incomplete), but the screening test set in vaccinated populations will shift further towards HPV-based methods as cytological abnormality rates fall.
Assessment
Screening is, by definition, applied to asymptomatic women — a woman with a symptom (postcoital, intermenstrual or postmenopausal bleeding, an offensive discharge, or a visibly abnormal cervix) is not a candidate for screening but for diagnostic work-up: she needs speculum examination, colposcopy and directed biopsy regardless of any screening result, because screening tests are designed to detect pre-invasive disease and a normal cytology or HPV result does not exclude an established cancer.
For the asymptomatic woman the "assessment" is the screen itself, applied with discipline:
- Confirm eligibility and HIV status. HIV status determines the schedule. An HIV-positive woman is screened at diagnosis and intensively thereafter. Document the date of the last screen.
- Take an adequate sample. For cytology, sample the transformation zone (ecto- and endocervix) with the SCJ visualised; an unsatisfactory smear must be repeated. For HPV testing, either a clinician-taken sample or a validated self-collected vaginal swab is acceptable — the latter is a deliberate strategy to reach women who decline or cannot access pelvic examination.
- Triage the positive screen, do not over-refer. A positive HPV result is triaged (HPV 16/18 genotype carries the highest risk and may go straight to colposcopy/treatment; other high-risk types are triaged by reflex cytology or VIA). An abnormal cytology result is mapped to action: low-grade results in young women may be repeated/HPV-triaged; HSIL warrants colposcopic assessment and treatment of the transformation zone.
- Recognise the limits of the test in front of you. VIA and colposcopy are unreliable when the SCJ has receded endocervically (post-menopause), where excisional assessment may be needed; cytology under-calls glandular and small invasive lesions; a single negative cytology is reassuring only across an interval, not absolutely.
The destination of a positive screen is colposcopic evaluation and histological confirmation, which is covered in colposcopy and cin-management; staging of established invasive disease follows FIGO 2018 (clinical examination supplemented by permitted imaging and pathology; nodal disease is stage IIIC) under the ESGO/ESTRO/ESP 2023 cervical cancer framework.
Management
"Management" of screening operates at two levels — the programme and the individual.
Programme level
The framework is WHO's 90–70–90 elimination target by 2030: 90% of girls fully HPV-vaccinated by age 15; 70% of women screened with a high-performance test (i.e. HPV-DNA, not cytology alone) by ages 35 and 45; and 90% of women with cervical disease treated. Reading the SA policy against this target is the substance of an exam answer. South Africa's historic three-lifetime-smears-from-30 model under-delivers against the "70% screened with a high-performance test at 35 and 45" pillar — hence the SASOG/BetterGyn 2024 push towards HPV primary screening, self-sampling to widen reach, and same-visit treatment to reduce loss-to-follow-up. The EML and NHLS capacity, plus the cost and logistics of HPV assays versus cytology, are the real-world constraints any policy must navigate.
Individual level — what you do with the result
- Screen-negative (HPV-negative / normal cytology): reassure and return at the policy-defined interval. HPV-negativity carries an excellent negative predictive value and is what licenses a long interval in HIV-negative women; in HIV-positive women the interval is shortened (≈3-yearly).
- Screen-positive, triage-positive (HSIL or HPV 16/18 with a lesion): treat the transformation zone. Thermal ablation is appropriate where the whole lesion and SCJ are visible, the lesion is ablation-eligible, and invasion is excluded; LLETZ (excision) is used where histology is needed, the lesion extends into the canal, the SCJ is not fully seen, or glandular/invasive disease is suspected. Detail in cin-management.
- Screen-positive, triage-negative: surveillance with repeat HPV/cytology rather than immediate treatment, to avoid over-treating transient infection (over-treatment of young women risks cervical incompetence and preterm birth in later pregnancies).
- Any suspicion of invasion: refer for colposcopy, biopsy and, if confirmed, gynaecological-oncology staging and multidisciplinary management — definitive treatment of locally advanced disease is concurrent chemoradiation (weekly cisplatin) plus image-guided brachytherapy (EMBRACE-II / GEC-ESTRO standards), now with pembrolizumab added to chemoradiation in high-risk locally advanced disease following KEYNOTE-A18, and pembrolizumab plus chemotherapy ± bevacizumab for recurrent/metastatic disease (KEYNOTE-826, PD-L1 CPS ≥1). These belong to the invasive-disease chapters but every screener must know that the point of screening is to make them unnecessary.
Red flags / pitfalls
- Treating screening as a diagnostic test in a symptomatic woman. Postcoital, intermenstrual or postmenopausal bleeding, or a visibly abnormal cervix, mandates colposcopy and biopsy — a recent "normal Pap" or negative HPV does not exclude cancer. This is the single most dangerous error and a recurrent cause of delayed cervical-cancer diagnosis.
- Forgetting the HIV exception. Applying the HIV-negative schedule (3 smears from age 30) to an HIV-positive woman is a serious under-screening error. HIV-positive women screen at diagnosis and frequently thereafter, regardless of age — including women in their twenties, who are excluded from the standard programme.
- Treating on a positive HPV test alone. A positive high-risk HPV result requires triage (genotyping/cytology/VIA) before treatment; jumping to ablation/LLETZ on the screen alone over-treats transient infection and risks future preterm birth.
- Quoting exact intervals as if fixed. SA policy is mid-transition from cytology-based to HPV-based primary screening. State the principle confidently; flag that precise age bands and intervals should be confirmed against the current BetterGyn 2024 / NDoH policy document.
- Inadequate sampling and ignoring the unsatisfactory result. A smear that misses the transformation zone or an unsatisfactory specimen must be repeated — a "normal" report on an inadequate sample is falsely reassuring.
- Loss to follow-up in a multi-visit pathway. The strongest argument for self-sampling and same-visit screen-and-treat in South Africa is that women referred onward frequently do not return. A perfect test that the woman never comes back for is worthless; programme design must minimise visits.
- The receded SCJ in older women. VIA and colposcopy lose reliability post-menopause when the SCJ is endocervical; do not falsely reassure — excisional assessment may be required.
Evidence anchors
- South African cervical cancer screening — SASOG / BetterGyn Clinical Guideline (2024), developed with the NDoH, plus the NDoH National Cervical Cancer Screening / Prevention & Control Policy: the SA source of truth. Direction of travel is HPV-DNA primary screening (informed by the DiaVACCS trial); historic public-sector policy is cytology, three smears 10-yearly from age 30; HIV-positive women screened at HIV diagnosis and ≈3-yearly thereafter regardless of age. Confirm exact intervals/algorithm against the current PDF before asserting numbers.
- WHO Cervical Cancer Elimination Strategy (2020) — 90–70–90 by 2030: 90% of girls HPV-vaccinated by 15; 70% of women screened with a high-performance test by 35 and 45; 90% with disease treated. Single-dose HPV schedule endorsed by WHO (2022) and adopted across Africa (SAGE/RITAG, Nov 2023); 9-valent vaccine = broadest cover; SA school-based HPV programme since 2014 (girls 9–14).
- ESGO/ESTRO/ESP Guidelines for cervical cancer — Update 2023 (Int J Gynecol Cancer): staging, fertility-sparing, early and locally advanced disease, radiotherapy and pathology principles. Staging = FIGO 2018 (imaging + pathology permitted; nodal disease = stage IIIC).
- WHO Classification of Tumours of the Female Genital Tract, 5th ed (2020): LSIL/HSIL terminology (LAST/2014) replacing CIN 1–3 in pathology; HPV-associated vs HPV-independent squamous lesions.
- Radiation oncology (cervical): definitive concurrent chemoradiation (weekly cisplatin) + image-guided brachytherapy for locally advanced disease; EMBRACE-II / GEC-ESTRO image-guided adaptive brachytherapy standards (cited here only to frame what screening aims to prevent).
- Medical oncology / immunotherapy (cervical): KEYNOTE-A18 — pembrolizumab + concurrent chemoradiation for high-risk locally advanced disease; KEYNOTE-826 — pembrolizumab + chemotherapy ± bevacizumab first-line recurrent/metastatic (PD-L1 CPS ≥1). Context for the downstream cost of failed prevention.