Cervical & Ovarian Cancer
A boards-focused pairing of cervical cancer (HPV-driven, screenable, prevented by vaccine, presents with postcoital bleeding) against ovarian cancer (BRCA/tubal-origin, no screening, late vague presentation, most lethal), emphasizing next-best-step decisions, classic markers, and buzzword histology.
Two cancers, two opposite stories
Cervical and ovarian cancer are the two most heavily tested gynecologic malignancies, and boards love them because their biology is a study in contrasts.
Cervical cancer is sexually transmitted oncogenesis. Persistent infection with high-risk HPV (types 16 and 18 cause ~70%) drives it: viral oncoproteins E6 (degrades p53) and E7 (inactivates Rb) release the cell-cycle brakes. Dysplasia (CIN) begins at the transformation zone (squamocolumnar junction) and progresses over years to invasive squamous cell carcinoma (most common) or adenocarcinoma. Because there is a long, detectable pre-invasive phase, cervical cancer is largely preventable by vaccination and screening.
Ovarian cancer is the mirror image: no effective screening, vague symptoms, and usually late-stage presentation — making it the most lethal gynecologic cancer. About 90% are epithelial (high-grade serous is commonest and deadliest, now known to arise from the fallopian tube fimbriae). The remainder are germ cell tumors (young women) and sex cord–stromal tumors, each with signature markers and syndromes.
- Cause: persistent high-risk HPV (16, 18 > 31, 33, 45). E6 → p53, E7 → Rb.
- Risk factors: early coitarche, multiple/high-risk partners, smoking, immunosuppression / HIV, long-term OCPs, high parity, inadequate screening.
- Presentation: often asymptomatic early; classic = postcoital (contact) bleeding, intermenstrual bleeding, malodorous or blood-tinged discharge.
- Advanced/complication: lateral extension → ureteral obstruction → hydronephrosis → post-renal failure (a leading cause of death); flank/back pain, leg edema.
- Screening (US): start at age 21 regardless of sexual history. 21–29: cytology q3y. 30–65: primary hrHPV q5y (preferred), co-testing q5y, or cytology q3y. Stop at 65 if adequate prior negative screening.
- Abnormal Pap → colposcopy + biopsy (± endocervical curettage).
- Prevention: 9-valent HPV vaccine, routine at 11–12 (catch-up to 26; shared decision 27–45). Vaccination does not change screening intervals.
Vignette: A 44-year-old woman reports postcoital bleeding and malodorous discharge for 3 months; she has not had a Pap in 12 years. Speculum exam shows a friable, exophytic 2-cm cervical mass that bleeds on contact.
- Most likely diagnosis: invasive cervical (squamous cell) carcinoma.
- Next best step: biopsy the visible lesion — not a Pap smear. A grossly visible/suspicious cervical lesion is worked up by direct biopsy; cytology can be falsely negative in frank cancer and only delays diagnosis.
- If instead the Pap were abnormal with no visible lesion, the next step is colposcopy with directed biopsy.
- After tissue diagnosis: exam + imaging (MRI/CT/PET) for FIGO staging (the 2018 revision incorporates imaging/pathology). Treat early disease surgically (radical hysterectomy + pelvic lymphadenectomy); treat locally advanced disease with cisplatin-based chemoradiation.
Board pearl: Don't screen a cancer you can already see — biopsy it.
- Epidemiology: most lethal gynecologic cancer (late presentation, no screening).
- Epithelial (~90% of malignant): high-grade serous = most common & deadliest, BRCA1/2-linked, arises from fallopian tube (STIC lesion), psammoma bodies, TP53 mutation. Others: mucinous, endometrioid, clear cell.
- Germ cell (young, teens–20s): dysgerminoma (↑LDH; most common malignant germ cell), yolk sac (↑AFP, Schiller-Duval bodies), choriocarcinoma (↑β-hCG), immature teratoma. Mature cystic teratoma (dermoid) is benign.
- Sex cord–stromal: granulosa cell (↑inhibin/estrogen, Call-Exner bodies → precocious puberty, endometrial hyperplasia/postmenopausal bleeding); Sertoli-Leydig (androgens → virilization); fibroma → Meigs syndrome (fibroma + ascites + right pleural effusion).
- Metastatic: Krukenberg = bilateral ovarian mets, signet-ring cells, usually gastric.
- Risk: BRCA1/2 (→ high-grade serous), Lynch (→ endometrioid/clear cell), nulliparity, early menarche/late menopause, age. Protective: OCPs, multiparity, breastfeeding, tubal ligation/salpingectomy.
- CA-125: monitors epithelial disease response/recurrence — not a screening test.
Ovarian tumor subtypes, markers & clues
| Category | Key tumor(s) | Marker / histology | Classic clue |
|---|---|---|---|
| Epithelial (~90%) | High-grade serous, mucinous, endometrioid, clear cell | CA-125; psammoma bodies (serous) | Older woman; BRCA; tubal (STIC) origin |
| Germ cell (young) | Dysgerminoma | ↑ LDH | Most common malignant germ cell |
| Yolk sac (endodermal sinus) | ↑ AFP; Schiller-Duval bodies | Child/adolescent | |
| Choriocarcinoma | ↑ β-hCG | Hematogenous spread | |
| Teratoma (immature) | — | Mature = benign dermoid | |
| Sex cord–stromal | Granulosa cell | ↑ inhibin/estrogen; Call-Exner bodies | Precocious puberty; postmenopausal bleeding |
| Sertoli-Leydig | Androgens | Virilization / hirsutism | |
| Fibroma | — | Meigs: ascites + pleural effusion |
Vignette: A 62-year-old postmenopausal woman has 4 months of bloating, early satiety, and increasing abdominal girth. Exam reveals a fixed, solid right adnexal mass and shifting dullness (ascites).
- Most likely diagnosis: epithelial ovarian cancer (classic vague, late presentation).
- Next best step: transvaginal ultrasound (± CA-125). Worrisome features: solid, complex/septated, thick walls, papillary projections, bilaterality, ascites, elevated CA-125.
- Do NOT perform percutaneous/needle biopsy of an adnexal mass — risks rupture and tumor seeding. Diagnosis and staging are surgical (exploratory laparotomy).
- Management: refer to gyn-onc for surgical staging + debulking (cytoreduction), then platinum-based chemo (carboplatin + paclitaxel); add a PARP inhibitor if BRCA-mutated.
- In a younger woman with a pelvic mass, order AFP, β-hCG, LDH to catch a germ cell tumor.
Psammoma bodies are laminated, concentric calcifications. Remember the classic four sites with "PSaMMoma":
- P — Papillary thyroid carcinoma
- S — Serous (papillary) cystadenocarcinoma of the ovary (also serous endometrial carcinoma)
- M — Meningioma
- M — Mesothelioma
In an ovarian vignette, psammoma bodies point to serous (epithelial) carcinoma — the BRCA-associated, tubal (STIC)-derived, CA-125-secreting tumor.
Cervical vs. ovarian cancer — side by side
| Feature | Cervical cancer | Ovarian cancer |
|---|---|---|
| Driver | High-risk HPV (16/18); E6/E7 | BRCA1/2, Lynch; tubal (STIC) origin |
| Commonest histology | Squamous cell carcinoma | High-grade serous (epithelial) |
| Screening | Yes — cytology/HPV (age 21–65) | None effective |
| Prevention | HPV vaccine + screening | OCPs, salpingectomy, risk-reducing BSO (BRCA) |
| Classic symptom | Postcoital bleeding | Bloating, early satiety, distension (late) |
| Tumor marker | (HPV testing) | CA-125 (monitoring, not screening) |
| Diagnosis | Biopsy visible lesion / colposcopy | Surgical (TVUS + CA-125 → laparotomy) |
| Key morbidity | Local → ureteral obstruction / renal failure | Transcoelomic → peritoneal/omental, ascites |
| Treatment | Surgery ± cisplatin chemoradiation | Debulking + carbo/paclitaxel ± PARP |
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