Clinical overview
Cervical intraepithelial neoplasia (CIN) is the pre-invasive squamous lesion of the cervix — the window in which cervical cancer is preventable rather than merely treatable. The disease you manage at this stage is the consequence of persistent high-risk human papillomavirus (hrHPV) infection driving dysplasia of the squamous epithelium, almost always at the transformation zone. In South Africa this is not a niche problem: cervical cancer is the leading cause of cancer death in women, the incidence is among the highest in the world, and the engine behind it is a generalised HIV epidemic that accelerates HPV persistence and progression. Getting CIN management right — detecting it, grading it accurately, treating the right lesions, and not over-treating the rest — is one of the highest-yield things a gynaecologist does in this country.
The registrar's task when "a patient presents with CIN" is rarely a single decision. You must integrate how she was detected (screen-detected hrHPV/cytology versus colposcopic biopsy), the histological grade in WHO-2020 terms (low-grade squamous intraepithelial lesion, LSIL ≈ CIN1; high-grade squamous intraepithelial lesion, HSIL ≈ CIN2–3), her HIV status and CD4, her age and fertility intentions, her access to follow-up, and whether the colposcopy was adequate and concordant. A coherent plan answers: does this lesion need treatment now, surveillance, or excision for diagnosis — and what is the follow-up that closes the loop so a missed cancer never walks out the door. This chapter assumes you understand the upstream biology covered in hpv-pathology, cin-pathophysiology and cervical-carcinogenesis, and the population screening machinery in cervical-screening-sa.
Core knowledge
Terminology: the two-tier WHO-2020 system and CIN equivalence
The WHO Classification of Tumours of the Female Genital Tract, 5th edition (2020), adopts the LAST/2014 two-tier nomenclature for HPV-associated squamous lesions, replacing the old three-tier CIN system. You must be fluent in both because South African laboratories and clinicians still speak in CIN:
| WHO-2020 / LAST | CIN equivalent | Biology |
|---|---|---|
| LSIL | CIN1 | Productive HPV infection; mostly transient |
| HSIL | CIN2 and CIN3 | Transforming infection; true precursor |
CIN2 is the deliberately ambiguous middle ground. Biologically it is a mix of regressing LSIL-like lesions and genuine HSIL, and reproducibility between pathologists is poor. p16 immunohistochemistry is the tiebreaker: a block-positive (diffuse, strong) p16 stain reclassifies an equivocal CIN2 as HSIL, while a negative/patchy stain supports LSIL and conservative management. This matters because over-calling CIN2 leads to over-treatment of young women whose lesions would have regressed.
Natural history and the numbers that drive decisions
LSIL/CIN1 is the cytological and histological footprint of a productive HPV infection. The majority regress — roughly 60% clear and only around 1% progress to invasion over years — which is why CIN1 is generally observed, not excised. HSIL/CIN2–3 is the transforming lesion: a meaningful proportion of untreated CIN3 (classically cited around a third or more over decades) progresses to invasive cancer, which is why HSIL is treated. The lag from persistent infection to invasion is typically a decade or more in an immunocompetent woman — the biological basis for unhurried screening intervals — but this assumption collapses in immunosuppression.
HIV: why South African CIN is different
This is the single most important contextual fact for an FCOG candidate. In women living with HIV, HPV is acquired more readily, cleared less often, and progresses faster; multiple high-risk genotypes coexist; CIN is more prevalent, higher-grade, more often multifocal (involving vagina and vulva), and recurs more frequently after treatment. Recurrence/residual disease rates after excision are substantially higher than in HIV-negative women, and lower CD4 counts worsen this further. The practical consequences run through every management decision: a lower threshold to treat, awareness that ablation may be less reliable, mandatory antiretroviral optimisation (TLD — tenofovir/lamivudine/dolutegravir — per the SA HIV Clinicians Society 2023 and SA National HIV/ART Consolidated Guidelines 2023), and tighter, lifelong follow-up. Effective ART reduces but does not abolish the excess risk.
The transformation zone and excision types
Treatment geography is everything. CIN arises at the transformation zone (TZ). Whether the squamocolumnar junction is fully visible determines whether colposcopy is "adequate" and which excision is appropriate. The IFCPC/BSCCP framework classifies excisions as Type 1 (TZ fully ectocervical/visible), Type 2 (TZ partly endocervical but visible), and Type 3 (TZ not fully visible, extends up the canal). A Type 3 excision (the old "cone") removes more canal and is required when disease extends endocervically, when glandular disease (AIS) is suspected, or when colposcopy is inadequate. See colposcopy for the technique itself.
Assessment
How she presented — and the cardinal rule
CIN is asymptomatic. A symptomatic cervix — post-coital bleeding, intermenstrual bleeding, offensive discharge, a visible or palpable lesion — is cancer until proven otherwise and must not be managed down a CIN pathway. The first assessment step is always to exclude invasion clinically.
Most patients reach you by one of two routes: (1) screen-positive (hrHPV-positive on the SA national programme, or abnormal cytology) referred for colposcopy, or (2) already biopsy-proven CIN referred for treatment or surveillance. Establish exactly which.
History
Confirm the screening/cytology/HPV result and any genotype (16/18 carry the highest risk). Take an HIV history — status, date of diagnosis, CD4 nadir and current, ART regimen and adherence, viral load — because it reframes the whole plan. Document age, parity, contraception, current pregnancy or fertility plans (excision carries obstetric risk), smoking (a cofactor for persistence), prior cervical treatment, and immunosuppression of any cause. Ask about symptoms specifically to flag possible invasion.
Examination and colposcopy
Figure D4.1 — Colposcopy: acetowhite change at the transformation zone, TZ Types 1–3, and the features that flag high-grade disease or invasion.
Speculum examination assesses the cervix directly — never assume the abnormality is purely cytological. Colposcopy after acetic acid (and Lugol's iodine) grades the lesion: acetowhite change, margins, vascular pattern (punctation, mosaic, atypical vessels), and the Swede or IFCPC score guide where to biopsy. Critically, you record whether the colposcopy is adequate (entire TZ and lesion margins seen) and whether the colposcopic impression is concordant with cytology/HPV. Discordance — for example high-grade cytology with a normal colposcopy — mandates further evaluation (repeat, top-of-canal sampling, or diagnostic excision), never reassurance.
Histology
Colposcopically directed punch biopsy gives the grade that drives management; report it in WHO-2020 terms with CIN equivalence and use p16 for equivocal CIN2. NHLS turnaround and the realities of public-sector follow-up shape whether "see-and-treat" (treat at the colposcopy visit on cytology/colposcopy grounds) is safer than a biopsy-then-recall pathway that loses women to follow-up — a recurring South African tension between diagnostic precision and loss to follow-up.
Management
Figure D4.2 — The CIN management algorithm: observe LSIL/CIN1 vs treat HSIL/CIN2–3, and thermal ablation vs LLETZ excision (with the never-ablate and over-treatment cautions).
A management plan must state: treat now, observe, or excise-to-diagnose — plus the follow-up that closes the loop. Counsel and consent throughout (informed-consent).
LSIL / CIN1 — observe
Confirmed LSIL/CIN1 with a fully visible TZ and concordant findings is observed, not treated, because most regress and excision carries obstetric morbidity. Surveillance is by HPV-based testing/cytology at intervals per the SASOG/BetterGyn 2024 SA cervical screening guideline and NDoH policy. Persistent CIN1 beyond roughly two years, or CIN1 with an unsatisfactory colposcopy/abnormal endocervical sampling, shifts the balance toward excision. In a woman living with HIV, the threshold to treat persistent low-grade disease is lower given faster progression and multifocality.
HSIL / CIN2–3 — treat
Confirmed HSIL is treated. Two modalities:
- Ablation (thermal ablation/cryotherapy) destroys the TZ in situ. It is appropriate only when colposcopy is adequate, the entire lesion and TZ are visible and ectocervical (Type 1), there is no suspicion of invasion or glandular disease, and cytology/histology concord. Thermal ablation is the WHO-endorsed, EML-available workhorse for screen-and-treat in lower-resourced SA settings.
- Excision (LLETZ — large loop excision of the transformation zone) removes the TZ and provides a specimen for histology, allowing assessment of margins and exclusion of occult invasion. LLETZ is preferred when the lesion extends into the canal (Type 2/3), when colposcopy is inadequate, when glandular disease (AIS) is suspected, when there is any concern about invasion, and as the safer default in women living with HIV given higher residual-disease rates. A Type 3 excision (cone) is used for endocervical extension or suspected AIS.
The key trade-off: ablation is quicker, cheaper, fertility-friendlier and ideal for screen-and-treat throughput, but yields no specimen — so it can never be used where invasion or glandular disease is a possibility. Excision is diagnostic and therapeutic but carries a dose-dependent risk of preterm birth and cervical insufficiency in future pregnancies (deeper/repeat excisions, larger volumes, worse risk) — counsel any woman of reproductive age explicitly. See cervical-screening-sa for how screen-and-treat is operationalised nationally.
CIN2 in young women who want fertility
Because CIN2 includes regressing lesions, observation (rather than immediate excision) is a reasonable option in selected young, immunocompetent women with HSIL/CIN2 (especially p16-negative or genotype-favourable), with close HPV/colposcopic surveillance and treatment if persistence or progression. This conservative pathway is NOT appropriate in women living with HIV, where progression risk dominates.
Adenocarcinoma in situ (AIS)
Glandular pre-invasive disease behaves differently: it is often endocervical, skip lesions occur, and ablation is contraindicated. AIS requires an excisional procedure (Type 3/cone) with clear margins, careful margin assessment, and a low threshold for hysterectomy once fertility is complete. Positive margins after AIS excision carry meaningful residual-invasion risk and mandate re-excision rather than surveillance.
HIV-specific management
Optimise ART (TLD; SAHCS 2023) in every HIV-positive woman with CIN — viral suppression and immune reconstitution reduce recurrence. Prefer excision over ablation given higher residual disease; accept that recurrence is common and build in lifelong, more frequent post-treatment surveillance. Manage multifocal lower-genital-tract disease (vagina/vulva) actively. The NDoH/national cervical screening policy explicitly directs that HIV-positive women are screened at HIV diagnosis and more frequently thereafter (≈3-yearly) regardless of age. See hiv-gynaecology.
Pregnancy
In pregnancy the aim is to exclude invasion and defer treatment. Colposcopy is performed by an experienced colposcopist; biopsy only if invasion is suspected; treat CIN definitively postpartum (≥6–8 weeks) once the cervix has involuted, because excision in pregnancy risks haemorrhage and pregnancy loss. See pregnancy-and-neoplasia.
Follow-up — the part that prevents cancers
Figure D4.3 — HPV-based test of cure after treating HSIL, the recurrence-risk factors, and how HIV changes follow-up.
The test of cure is HPV-based. After treatment of HSIL, follow-up co-testing/HPV testing (e.g. at 6 and ~12–24 months per SASOG/BetterGyn 2024) detects residual/recurrent disease; a negative hrHPV test of cure is the strongest reassurance. HPV-positive or cytologically abnormal follow-up returns the woman to colposcopy. Margin status, endocervical involvement, age >50, and HIV all raise recurrence risk and tighten surveillance. Women treated for HSIL remain at elevated cancer risk for decades and require long-term follow-up — they are never simply discharged to routine screening immediately.
Primary prevention as part of the plan
A CIN consultation is also a prevention opportunity. The WHO Cervical Cancer Elimination Strategy (2020) sets the 90-70-90 targets for 2030 (90% of girls HPV-vaccinated by 15; 70% of women screened with a high-performance test by 35 and 45; 90% of those with disease treated). South Africa's school-based HPV vaccination programme (girls 9–14 since 2014) and the WHO-endorsed single-dose schedule sit upstream of every CIN you treat; the nonavalent vaccine gives broadest coverage. Vaccination is prophylactic, not therapeutic, but counsel about household/eligible vaccination and reinforce screening uptake.
Red flags / pitfalls
- Treating a symptomatic cervix as CIN. Post-coital/intermenstrual bleeding or a visible lesion is cancer until excluded. Never ablate or LLETZ a suspicious cervix without excluding invasion.
- Ablating when you cannot see the whole TZ, when disease is endocervical, or when AIS is possible. Ablation destroys the evidence — you can ablate an occult cancer. Inadequate colposcopy, Type 3 lesions, glandular disease and any invasion concern all demand excision.
- Cytology/colposcopy discordance treated as reassurance. High-grade cytology with normal colposcopy is not a normal result — it is incomplete evaluation. Sample the canal / diagnostic excision.
- Over-treating LSIL/CIN1 and young CIN2. Excising lesions that would regress imposes preterm-birth risk for no oncological gain. Use p16 to adjudicate CIN2; observe where appropriate.
- Forgetting HIV reframes everything. Assuming immunocompetent natural history in an HIV-positive woman under-treats and under-follows her. Optimise ART, prefer excision, follow lifelong.
- Loss to follow-up. In SA the commonest way CIN becomes cancer is a woman who never returns. Weigh see-and-treat against biopsy-then-recall realistically, and build robust recall.
- No HPV test of cure. Discharging a treated woman without a documented negative hrHPV follow-up misses residual disease — the highest-risk window for invasion.
- Ignoring positive excision margins (especially AIS / endocervical). These predict residual disease and need re-excision or stricter surveillance, not reassurance.
- Counselling failure on fertility. Not warning a young woman about the cumulative preterm-birth risk of deep/repeat excision is a consent failure.
Evidence anchors
- SASOG / BetterGyn Clinical Guideline for cervical cancer screening (2024) and NDoH National Cervical Cancer Screening / Prevention & Control Policy — the South African source of truth: the move toward HPV-DNA primary screening (informed by the DiaVACCS trial), HPV → triage → treat (thermal ablation or LLETZ) pathway, screen-and-treat, HIV-positive screening at diagnosis and ≈3-yearly thereafter regardless of age, and post-treatment HPV-based test of cure. Confirm exact intervals/algorithm against the current PDF before asserting numbers.
- WHO Cervical Cancer Elimination Strategy (2020) — 90-70-90 by 2030, single-dose HPV schedule (WHO 2022; adopted across Africa), nonavalent vaccine for broadest cover; South African school-based programme since 2014.
- WHO Classification of Tumours of the Female Genital Tract, 5th edition (2020) — LAST/2014 two-tier LSIL/HSIL terminology replacing CIN1–3, HPV-associated lesions, and the role of p16 in adjudicating equivocal CIN2.
- ESGO/ESTRO/ESP Guidelines for cervical cancer — Update 2023 — principles of staging (FIGO 2018), the management of frankly invasive disease that CIN treatment must exclude, fertility-sparing principles, and cancer in pregnancy.
- South African HIV Clinicians Society Adult ART Guidelines (2023) and SA National HIV/ART Consolidated Guidelines (2023) — TLD (TDF + 3TC + DTG) as first-line ART, the basis for optimising immune status in HIV-positive women with CIN; SA EML for thermal ablation/LLETZ availability and NHLS for histology turnaround.