Clinical overview
Cancer complicates roughly one in a thousand pregnancies, and the question the exam wants you to answer is bidirectional: what does pregnancy do to the neoplasm, and what does the neoplasm — and its treatment — do to the pregnancy. In South Africa this is not an academic curiosity. We are a young, high-fertility population superimposed on the world's largest HIV epidemic, and the commonest cancer diagnosed during pregnancy here is cervical cancer, precisely because HPV-driven disease is accelerated by immunosuppression and our screening coverage remains below the WHO 90-70-90 targets. Breast cancer, thyroid cancer, melanoma, lymphoma/leukaemia and ovarian neoplasms make up most of the remainder. A registrar will meet the abnormal smear in the antenatal clinic, the adnexal mass on the dating scan, and the persistently raised βhCG after a "miscarriage" that turns out to be a molar pregnancy.
The central teaching point is that pregnancy is rarely the cause of a worse cancer outcome — stage-for-stage, prognosis is usually equivalent to the non-pregnant patient — but it powerfully modifies detection, investigation and treatment. Physiological breast and pelvic changes mask early signs and delay diagnosis; ionising radiation and many cytotoxics threaten the fetus, especially in the first trimester; and the emotional and ethical weight of balancing two lives demands genuine multidisciplinary, patient-centred decision-making. The skill being tested is the ability to hold maternal oncological benefit and fetal safety in the same frame and arrive at a defensible plan.
Core knowledge
How pregnancy might influence tumour biology
Figure D15.1 — How pregnancy affects neoplasia: hormone-sensitive growth, immune tolerance, vascular/lymphatic boost, diagnostic masking, and placental/fetal metastasis (melanoma).
Several physiological features of pregnancy are theoretically pro-neoplastic, and you should be able to reason through them rather than memorise a verdict.
- Hormonal milieu. Oestrogen, progesterone and prolactin rise enormously. For hormone-receptor-positive tumours (a subset of breast cancer, low-grade endometrial-type lesions, some ovarian sex-cord tumours) this is a plausible growth stimulus, though pregnancy-associated breast cancers are more often receptor-negative and high-grade — partly a biological feature of younger women rather than a hormonal effect.
- Immune modulation. Pregnancy induces a tolerogenic state (shift toward regulatory T cells, altered Th1/Th2 balance) that protects the semi-allograft fetus but may also blunt anti-tumour surveillance. This matters most for immunogenic and virally-driven tumours.
- Angiogenesis and vascular permeability. Pregnancy is a pro-angiogenic, hyperdynamic state (rising VEGF, increased plasma volume and cardiac output), which could theoretically support tumour growth and dissemination.
- Mechanical and lymphatic changes. Increased pelvic and breast vascularity and lymphatic flow are invoked to explain occasional rapid progression, but the evidence that pregnancy genuinely accelerates metastasis is weak for most tumours.
Against this, large series and the ESGO/ESTRO/ESP cervical guideline (Update 2023) — which contains a dedicated cancer-in-pregnancy section — conclude that stage-matched survival is not demonstrably worse for cervical cancer diagnosed in pregnancy. The dominant clinically observable effect is delayed diagnosis, not accelerated biology.
Cervical neoplasia — the SA-relevant centrepiece
Figure D15.2 — Pregnancy-associated cancers and the cervical-cancer-in-pregnancy pathway (ESGO/ESTRO/ESP 2023): individualised by stage, gestational age and the woman's wishes.
Pregnancy is, for many women, their only sustained contact with the health system, making the antenatal visit a screening opportunity that the SASOG/BetterGyn 2024 guideline and NDoH cervical screening policy explicitly endorse. Use WHO 2020 / LAST terminology: LSIL (≈ CIN 1) and HSIL (≈ CIN 2–3), HPV-associated.
Key biological facts:
- HSIL does not progress to invasion during the pregnancy interval. Cytological "regression" postpartum is well described and partly reflects sampling and the transformation-zone eversion of pregnancy rather than true cure.
- Decidualisation of the cervical stroma can mimic dysplasia or invasion both cytologically and colposcopically — a classic pitfall. The transformation zone is everted and more accessible, which aids colposcopy but increases bleeding.
- HIV (high local prevalence) drives both higher HPV-HSIL incidence and faster progression; HIV-positive pregnant women warrant a low threshold to evaluate. The HIV-positive screening rule — screen at diagnosis and approximately 3-yearly regardless of age — is unchanged by pregnancy.
For invasive disease, FIGO 2018 staging applies (IA microscopic by depth ≤5 mm; IB by size; nodal disease = IIIC). MRI without gadolinium is the preferred imaging in pregnancy for local extent.
Ovarian and adnexal neoplasms
Most adnexal masses found in pregnancy are benign and physiological or functional (corpus luteum, theca-lutein cysts), and the majority resolve by the second trimester. Among persistent masses, mature cystic teratoma and benign cystadenoma dominate. Malignancy is uncommon (roughly 1–6% of persistent masses); when present, germ-cell tumours and borderline epithelial tumours are over-represented relative to the older non-pregnant population. See adnexal-mass-in-pregnancy and ultrasound-malignancy-signs. CA-125 and many tumour markers (AFP, βhCG, inhibin) are physiologically altered by pregnancy and must be interpreted with great caution.
Gestational trophoblastic disease and neoplasia
This is the one neoplastic process that arises from the pregnancy itself, and it is uniquely important. Complete hydatidiform mole is diploid androgenetic (46XX); partial mole is triploid. Gestational trophoblastic neoplasia (GTN) is defined by persistently rising or plateaued βhCG after evacuation, or by choriocarcinoma/PSTT/ETT. Choriocarcinoma is the malignant trophoblastic tumour that may follow any pregnancy event (mole, miscarriage, term delivery) and characteristically presents with haemorrhagic metastases (lung, brain, vagina). GTN is staged by FIGO 2000 anatomical staging (I–IV) plus the modified WHO prognostic score, and is exquisitely chemosensitive (see gtd-diagnosis and gtd-pathology).
Breast, melanoma and other tumours
Pregnancy-associated breast cancer is masked by physiological engorgement and is often diagnosed late and at higher stage; melanoma may darken or enlarge naevi physiologically but pregnancy does not convincingly worsen melanoma prognosis stage-for-stage. Both can metastasise to the placenta (melanoma is the commonest tumour to do so), mandating placental histology when maternal metastatic disease is present.
Assessment
Recognising malignancy against a physiological background
The diagnostic challenge is that pregnancy mimics and masks. Weight loss is unexpected; persistent or escalating pain, an enlarging fixed mass, abnormal bleeding beyond a reasonable obstetric explanation, lymphadenopathy and unexplained anaemia should all prompt investigation rather than reassurance. Do not attribute postcoital or persistent vaginal bleeding to "a friable cervix of pregnancy" without a speculum examination — a visible cervical lesion needs biopsy.
Cytology, colposcopy and biopsy in pregnancy
- Screening: an abnormal smear in pregnancy is managed by colposcopy, not by deferring assessment, when high-grade disease or invasion is suspected.
- Colposcopy is safe; the everted transformation zone aids visualisation but bleeds readily, and decidual change can be misread as high-grade disease or invasion (the principal pitfall — see colposcopy).
- Excisional procedures (LLETZ/cone) carry real risk in pregnancy — haemorrhage, miscarriage, preterm birth — and are reserved for ruling out invasion when microinvasion or worse is suspected, ideally in the second trimester. Endocervical curettage is contraindicated.
- HSIL without invasion is followed, not treated, during pregnancy, with definitive treatment deferred to a postpartum reassessment (typically about 6–8 weeks after delivery), because of the high postpartum regression rate and the absence of progression to cancer over the pregnancy interval. See cin-management.
Imaging — minimising fetal dose
The governing principle is to use the least harmful modality that answers the question.
- Ultrasound and MRI (without gadolinium) are the workhorses — no ionising radiation; MRI is excellent for local staging of cervical and pelvic tumours. Gadolinium crosses the placenta and is avoided.
- Ionising radiation: the fetus is most vulnerable in the first trimester (organogenesis, miscarriage, malformation) and the conceptus carries a lifetime stochastic cancer risk. Most diagnostic studies with appropriate abdominal shielding deliver well below thresholds for deterministic harm, but PET-CT and CT abdomen/pelvis are avoided where MRI/ultrasound can substitute. A chest radiograph with shielding delivers a negligible fetal dose and is acceptable when staging the chest is essential.
Tumour markers and staging caveats
CA-125, AFP, βhCG, inhibin and others are physiologically elevated or unreliable in pregnancy; serial trends after definitive intervention are more useful than single values. In GTN, by contrast, βhCG is the central, quantitative marker of disease activity, response and surveillance.
Management
Figure D15.3 — Managing cancer in pregnancy: pregnancy-safe staging imaging, chemotherapy from the 2nd trimester, radiotherapy avoidance, delivery timing, and the MDT.
Management hinges on three variables held together: tumour type and stage, gestational age, and the patient's informed wishes. Decisions are made by a multidisciplinary team — gynaecological oncology, medical and radiation oncology, obstetrics/maternal-fetal medicine, neonatology and the patient — and documented with explicit informed-consent. The default goal, wherever oncologically safe, is to treat the mother effectively while allowing the pregnancy to reach a viable, ideally near-term, gestation.
Trimester-based principles for systemic and radiation therapy
- Chemotherapy is contraindicated in the first trimester (teratogenesis, organogenesis, fetal loss). From the second trimester onward, several regimens can be given with acceptable fetal safety, though with increased fetal growth restriction and a need to time delivery away from cytotoxic nadirs (avoid chemotherapy after ~33–35 weeks so maternal and neonatal counts recover before birth).
- Pelvic/abdominal radiotherapy is incompatible with continuing an intrauterine pregnancy — definitive cervical chemoradiation cannot be delivered with a viable fetus in situ. Antineoplastic agents and pelvic radiation are EML-listed but their use in pregnancy is individualised by the MDT.
- Targeted/immunotherapy agents (immune checkpoint inhibitors, anti-angiogenics) are generally avoided in pregnancy on safety grounds; the pivotal trials below were conducted in non-pregnant populations and do not license pregnancy use.
Cervical cancer in pregnancy
Decisions follow the ESGO/ESTRO/ESP 2023 cancer-in-pregnancy framework, individualised to stage and gestation:
- Microinvasive / very early stage (e.g. IA), gestation allowing: cone/trachelectomy or close surveillance with definitive treatment after delivery may be feasible, prioritising pregnancy continuation.
- Locally advanced disease diagnosed early, where the woman wishes to continue: neoadjuvant platinum-based chemotherapy (from the second trimester) can control disease and allow the pregnancy to reach viability, with definitive treatment (radical surgery, or concurrent chemoradiation with weekly cisplatin plus image-guided brachytherapy, EMBRACE-II/GEC-ESTRO standards) delivered postpartum.
- Advanced disease where immediate definitive treatment is required and/or the woman does not wish to continue: chemoradiation proceeds, which is not compatible with an ongoing viable pregnancy.
- Mode and timing of delivery: for invasive cervical cancer, caesarean section is generally preferred (vaginal delivery risks haemorrhage, obstruction and tumour implantation in episiotomy/lacerations), and definitive surgery can be combined with caesarean (e.g. caesarean radical hysterectomy). Delivery is timed to fetal maturity balanced against maternal disease.
The newer agents on the verified list — pembrolizumab added to chemoradiation (KEYNOTE-A18) for high-risk locally advanced disease, and pembrolizumab plus chemotherapy ± bevacizumab first-line for recurrent/metastatic disease (KEYNOTE-826, PD-L1 CPS ≥1) with cemiplimab as a second-line option — define modern non-pregnant cervical cancer care and are relevant to the postpartum or metastatic setting, but are not used during pregnancy.
Ovarian/adnexal masses
Most are observed; surgery is reserved for the symptomatic (torsion, rupture), the persistently large, or the radiologically suspicious mass. When operative intervention is needed, the second trimester is the safest window. Germ-cell and borderline tumours predominate among the malignant minority, and platinum/taxane chemotherapy from the second trimester is feasible when adjuvant treatment is required.
Gestational trophoblastic neoplasia
GTN is the success story of chemosensitivity and the most curable gynaecological malignancy. Treatment is risk-stratified by the FIGO 2000 stage + modified WHO prognostic score (per RCOG GTG 38):
| Risk group | WHO prognostic score | First-line chemotherapy |
|---|---|---|
| Low risk | ≤ 6 | Single-agent — methotrexate (± folinic acid) or actinomycin-D |
| High risk | ≥ 7 (and stage IV) | Multi-agent — EMA-CO |
Cure rates exceed 90%. βhCG guides response and surveillance; the UK central-registration model informs SA practice. See gtd-diagnosis.
South African service realities
NHLS turnaround for histology and HPV testing, distances to tertiary gynaecological-oncology and radiation-oncology centres, and the competing demand on scarce MRI capacity all shape what is achievable. The antenatal clinic remains an under-used screening contact point; embedding HPV-based screening and decidualisation-aware colposcopy into antenatal care directly serves the WHO 90-70-90 elimination agenda in a population where late presentation is the rule.
Red flags / pitfalls
- Attributing red-flag symptoms to "normal pregnancy." Postcoital/persistent bleeding, an enlarging fixed mass, weight loss or lymphadenopathy demand investigation. Always do a speculum exam — visible cervical lesions need biopsy, not reassurance.
- Mistaking decidualised cervix or stroma for dysplasia or invasion on cytology, colposcopy or histology — over-call leads to harmful intervention.
- Over-treating HSIL in pregnancy. It does not progress to cancer over the pregnancy interval and frequently regresses postpartum; the role of antenatal evaluation is to exclude invasion, not to treat dysplasia. Endocervical curettage is contraindicated; excisional procedures risk haemorrhage and preterm birth.
- First-trimester chemotherapy or any pelvic radiotherapy with a continuing viable pregnancy — both are unacceptable; sequence therapy to gestation.
- Gadolinium contrast and avoidable CT/PET-CT — substitute non-contrast MRI and ultrasound.
- Misreading pregnancy-altered tumour markers (CA-125, AFP, βhCG) as evidence of disease activity in non-trophoblastic tumours.
- Forgetting placental and neonatal assessment in maternal metastatic disease — melanoma is the classic placental/fetal metastasiser; send the placenta for histology.
- Vaginal delivery with invasive cervical cancer — risks catastrophic haemorrhage and episiotomy-site implantation; caesarean is generally preferred.
- Missing GTN — investigate persistently raised or plateauing βhCG after any pregnancy event; do not dismiss it as retained products.
Evidence anchors
- ESGO/ESTRO/ESP Guidelines for cervical cancer — Update 2023 (Int J Gynecol Cancer) — includes a dedicated cancer-in-pregnancy section; staging by FIGO 2018.
- SASOG / BetterGyn Clinical Guideline (2024) on South African cervical cancer screening + NDoH National Cervical Cancer Screening / Prevention & Control Policy — antenatal screening opportunity; HIV-positive women screened at diagnosis and ~3-yearly regardless of age.
- WHO Cervical Cancer Elimination Strategy (2020) — 90-70-90 by 2030.
- EMBRACE-II / GEC-ESTRO image-guided adaptive brachytherapy standards; definitive cervical chemoradiation = weekly cisplatin + image-guided brachytherapy (delivered postpartum, not with a viable pregnancy in situ).
- KEYNOTE-A18 (pembrolizumab + chemoradiation, high-risk locally advanced) and KEYNOTE-826 (pembrolizumab + chemo ± bevacizumab, recurrent/metastatic, PD-L1 CPS ≥1); cemiplimab second-line — modern non-pregnant cervical cancer care.
- RCOG Green-top Guideline No. 38 — Gestational Trophoblastic Disease (4th edition, 2020) — GTN definition, FIGO 2000 staging + modified WHO score, single-agent (methotrexate/actinomycin-D) vs multi-agent (EMA-CO).
- FIGO GTD 2021 update (Ngan HYS et al., Int J Gynecol Obstet 2021;155(Suppl 1):86–93) — current FIGO management reference; retains FIGO 2000 staging + modified WHO score, adds ultra-high-risk (≥13) low-dose etoposide–cisplatin induction.
- WHO Classification of Tumours of the Female Genital Tract, 5th ed (2020) — LSIL/HSIL (LAST/2014) terminology replacing CIN 1–3; HPV-associated vs HPV-independent typing; trophoblastic and ovarian tumour classification.
- South African EML — Hospital Level (Adults) — antineoplastic agents; use in pregnancy individualised by the MDT.