Gynecological Oncology

Three cancers dominate this subject, and they are usually learned as three unrelated lists of stages and treatments.

The organising tool is to name the driver first. Cervical cancer is driven by a virus. Endometrial cancer is driven by unopposed oestrogen. Ovarian cancer is driven by ovulation and by inherited mutation.

Once the driver is named, almost everything else is deducible.

A virus can be vaccinated against and detected before it causes cancer, so cervical cancer is screenable and preventable. Unopposed oestrogen produces bleeding early, so endometrial cancer presents at an early stage and does well. Ovulation happens silently inside the pelvis, so ovarian cancer produces no early symptom, has no useful screening test and presents late.

Those three sentences explain why the same subject contains the most preventable gynaecological cancer and the most lethal one.

1. Cervical Cancer and Its Virus

Persistent infection with high-risk human papillomavirus, principally types 16 and 18, causes essentially all cervical cancer.

The virus produces two oncoproteins with defined targets. E6 degrades p53 and E7 inactivates the retinoblastoma protein, removing the two principal brakes on the cell cycle, which is why this is one of the clearest examples of viral carcinogenesis in medicine.

Most infections clear spontaneously within two years. Cancer requires persistence, and the cofactors that permit it are smoking, immunosuppression including advanced human immunodeficiency virus infection, high parity, long-term combined oral contraceptive use and coexisting sexually transmitted infection.

The natural history is slow, typically a decade or more from persistent infection through cervical intraepithelial neoplasia to invasive cancer. That long preinvasive window is the entire reason screening works.

The transformation zone, where columnar epithelium of the endocervix meets squamous epithelium of the ectocervix, is where metaplasia occurs and where the virus establishes itself, so it is the target of every screening and treatment method.

Squamous cell carcinoma is the commonest histological type, with adenocarcinoma second and less well detected by cytology because it arises higher in the canal.

Presentation is postcoital bleeding, intermenstrual bleeding, offensive discharge, and in advanced disease pelvic pain, leg swelling from lymphatic obstruction and renal failure from bilateral ureteric obstruction.

Death in advanced cervical cancer is commonly from uraemia, because the tumour spreads laterally through the parametrium and obstructs both ureters.

2. Screening and Prevention in India

Cytology detects abnormal cells, whereas human papillomavirus testing detects the cause, and testing for the virus is more sensitive and allows longer screening intervals.

Visual inspection with acetic acid is the method used in India's public programme, because it requires no laboratory, gives an immediate result and can be performed by trained health workers. Abnormal epithelium turns acetowhite.

Its sensitivity is lower than cytology or virus testing, but a test that reaches the population beats a better test that does not, and this trade-off is the reason for the choice.

Colposcopy with directed biopsy follows an abnormal screen. Preinvasive disease is treated by excision of the transformation zone, most often by large loop excision, which is both diagnostic and therapeutic.

Cervical intraepithelial neoplasia is graded by how much of the epithelial thickness is replaced by atypical cells: the lower third in grade 1, two-thirds in grade 2 and the full thickness in grade 3, with the basement membrane still intact throughout.

That last clause is the whole point. Nothing has invaded, so complete local excision is curative, and this is why treating grade 3 disease prevents a cancer rather than treating one.

Grade 1 lesions regress spontaneously in the majority of young women and are usually followed rather than excised, whereas grades 2 and 3 are treated. Excision carries a small increase in the risk of preterm birth in later pregnancy, which is why over-treating a lesion that would have regressed is not harmless.

India launched a nationwide human papillomavirus vaccination programme in February 2026, giving a single free dose to girls aged 14, targeting around 1.15 crore girls annually with Gardasil supplied through GAVI.

The single-dose schedule reflects evidence that one dose gives protection comparable to two in this age group, and it makes a national programme logistically feasible in a way a three-dose schedule never was.

Vaccination is given before sexual debut because it prevents infection and does not clear established infection. Vaccination does not remove the need for screening, because the vaccine does not cover every oncogenic type.

3. Staging and Treating Cervical Cancer

The FIGO 2018 revision changed cervical staging fundamentally by allowing imaging and pathology to determine stage, where previously staging was strictly clinical.

Stage IB is now subdivided by size: IB1 under 2 centimetres, IB2 from 2 to under 4, and IB3 at 4 centimetres or more. Nodal disease creates stage IIIC, with IIIC1 for pelvic nodes and IIIC2 for para-aortic nodes.

A notation of r or p records whether the stage was assigned by imaging or by pathology, which preserves transparency about how the conclusion was reached.

Treatment follows stage. Very early disease may be treated by conisation or simple hysterectomy, and fertility-sparing trachelectomy is possible in selected small tumours.

Early invasive disease is treated by radical hysterectomy with pelvic lymphadenectomy, which removes the parametrium and upper vagina as well as the uterus.

Locally advanced disease is treated with concurrent chemoradiation rather than surgery, using cisplatin as a radiosensitiser, and adding surgery to chemoradiation increases morbidity without improving survival.

4. Endometrial Cancer and Unopposed Oestrogen

Endometrial carcinoma is the commonest gynaecological cancer in high-income countries and is rising in India with obesity.

Every classical risk factor is a mechanism for oestrogen unopposed by progesterone: obesity through peripheral aromatisation in adipose tissue, nulliparity and early menarche with late menopause through more ovulatory cycles, polycystic ovary syndrome through anovulation, oestrogen-only hormone therapy, and tamoxifen through its agonist effect on the endometrium.

Diabetes and hypertension accompany the obesity rather than acting independently.

The protective factors are the mirror image: combined oral contraceptives, pregnancy and smoking, all of which reduce endometrial oestrogen exposure.

Type 1 tumours are endometrioid, oestrogen-driven, arise from hyperplasia, are usually low grade and have a good prognosis. Type 2 tumours, principally serous and clear cell, are not oestrogen-driven, arise in atrophic endometrium in older women, are high grade and behave aggressively.

Postmenopausal bleeding is endometrial cancer until proved otherwise, and it is the reason this cancer presents early.

Assessment is by transvaginal ultrasound measuring endometrial thickness, with a threshold of about 4 millimetres in a postmenopausal woman below which cancer is very unlikely, followed by endometrial sampling where the endometrium is thickened or bleeding persists.

Atypical hyperplasia is the true precursor and carries a substantial risk of coexisting carcinoma, which is why it is treated by hysterectomy rather than observed, with progestogens reserved for women wishing to preserve fertility.

5. FIGO 2023 and Molecular Classification

The FIGO 2023 revision incorporated molecular classification into endometrial cancer staging, which is the most significant change in this subject in a generation.

Four molecular groups are recognised, and each carries a different prognosis.

When the molecular subtype is known it is recorded in the stage with the letter m and a subscript, and in early-stage disease it can change the stage itself.

A POLE-mutated tumour is downstaged and a p53-abnormal tumour is upstaged, because the biology predicts outcome better than the anatomy does in those two groups.

The 2023 revision also separates micrometastasis from macrometastasis in nodal disease, subdividing stage IIIC accordingly.

Mismatch repair deficiency has a further implication beyond prognosis, because it identifies Lynch syndrome, which requires family screening and predicts response to immunotherapy.

Treatment is hysterectomy with bilateral salpingo-oophorectomy and nodal assessment, with adjuvant radiotherapy or chemotherapy according to risk.

6. Ovarian Cancer and Why It Presents Late

Epithelial ovarian cancer accounts for the great majority of ovarian malignancy and has the highest mortality of the gynaecological cancers.

The incessant ovulation hypothesis explains the risk factors. Each ovulation ruptures and repairs the surface epithelium, and more lifetime ovulations means more opportunity for mutation, which is why nulliparity and early menarche with late menopause increase risk while pregnancy, lactation and the combined oral contraceptive pill are protective.

The pill is one of the strongest protective factors in oncology, and the protection persists for decades after stopping.

BRCA1 and BRCA2 mutations account for a substantial minority of cases and cluster with breast cancer in families. There is good evidence that many high-grade serous carcinomas actually arise in the fimbrial end of the fallopian tube rather than the ovary itself.

Ovarian cancer presents late because the pelvis accommodates a growing mass silently. Symptoms are bloating, early satiety, urinary urgency and vague abdominal discomfort, all of which are common and non-specific, and most patients present at stage 3 with peritoneal disease and ascites.

Population screening does not work. Neither CA-125 nor ultrasound has sufficient specificity in a disease of low prevalence, and trials have not shown a mortality benefit, so screening is offered only to high-risk women such as BRCA carriers.

CA-125 is used for monitoring and for the risk of malignancy index, not for diagnosis, and it rises in endometriosis, fibroids, pelvic infection, pregnancy and any peritoneal irritation.

Risk-reducing bilateral salpingo-oophorectomy after childbearing is offered to BRCA carriers and substantially reduces both ovarian and breast cancer risk.

Treatment is cytoreductive surgery with platinum and taxane chemotherapy, and the volume of residual disease after surgery is among the strongest predictors of survival, which is why the operation aims at leaving no visible tumour.

7. Ovarian Tumour Types and Their Markers

Ovarian tumours are classified by cell of origin, and the age of the patient is the most useful first clue.

Germ cell tumours occur in young women and are usually curable, which is the opposite of the epithelial pattern, so the age of the patient changes the entire outlook.

Mature cystic teratoma, the dermoid cyst, is the commonest ovarian tumour in young women and is benign. Struma ovarii is a teratoma composed of thyroid tissue and can cause thyrotoxicosis.

Granulosa cell tumours secrete oestrogen, producing precocious puberty in girls and postmenopausal bleeding in older women, and they can therefore present with endometrial hyperplasia. Sertoli-Leydig tumours secrete androgens and cause virilisation.

Meigs syndrome is the combination of a benign ovarian fibroma with ascites and a pleural effusion, both of which resolve after removing the tumour.

Krukenberg tumour is bilateral ovarian metastasis with signet ring cells, classically from a gastric primary.

8. Gestational Trophoblastic Disease

A complete mole arises when an empty ovum is fertilised, has a diploid entirely paternal karyotype, contains no fetal tissue, and shows diffuse villous swelling with a snowstorm appearance on ultrasound.

A partial mole is triploid, contains some fetal tissue, and has a much lower malignant potential.

Presentation is early pregnancy bleeding with a uterus large for dates, hyperemesis, and a human chorionic gonadotropin level far above that expected.

Because the hormone is structurally similar to thyroid stimulating hormone, very high levels can cause thyrotoxicosis, and early pre-eclampsia before 20 weeks in a molar pregnancy is another recognised consequence.

Treatment is suction evacuation with subsequent monitoring of the hormone level to detect persistent trophoblastic disease. Pregnancy is avoided during follow-up because a rising hormone level would then be uninterpretable.

Choriocarcinoma is highly chemosensitive and curable even with metastases, which makes it unusual among malignancies and is the reason follow-up is worth its inconvenience.

9. Vulvar and Vaginal Cancer

Vulvar carcinoma is uncommon and is usually squamous, and it has two quite separate causal routes that map onto two different age groups.

The younger route is viral, driven by human papillomavirus through vulvar intraepithelial neoplasia, and it occurs in women in their forties and fifties who often have other virus-related lesions.

The older route is inflammatory, arising in longstanding lichen sclerosus, and it occurs in women in their seventies and eighties on a background of years of itching and white atrophic skin.

The presentation is a persistent lump, ulcer or itch, and the commonest error is treating chronic vulvar itching with repeated courses of topical steroid or antifungal without ever examining or biopsying the skin.

Spread is to inguinofemoral nodes, and nodal status is the dominant prognostic factor. Treatment is wide local excision with groin node assessment, using sentinel node biopsy in selected early cases to spare the substantial lymphoedema that full groin dissection causes.

Primary vaginal cancer is rare, and most vaginal malignancy is metastatic or direct extension from the cervix or vulva. Clear cell adenocarcinoma of the vagina in a young woman is the classic consequence of intrauterine diethylstilbestrol exposure, now of historical rather than practical importance.

10. Worked Examples

Example 1. A 58-year-old obese woman has a single episode of postmenopausal bleeding. Transvaginal ultrasound shows an endometrial thickness of 9 millimetres.

Postmenopausal bleeding is endometrial cancer until proved otherwise, and obesity supplies the mechanism through peripheral aromatisation of androgens to oestrogen in adipose tissue.

An endometrial thickness above about 4 millimetres in a postmenopausal woman requires tissue, so endometrial sampling or hysteroscopy with biopsy is the next step. A thin endometrium would have made cancer very unlikely, but 9 millimetres does not permit reassurance.

Example 2. A 62-year-old woman has abdominal distension, early satiety and ascites, with a CA-125 of 800.

This is the classic late presentation of epithelial ovarian cancer, and the vagueness of the symptoms is precisely why it presented at this stage.

CA-125 supports the diagnosis but does not establish it, since it rises with any peritoneal irritation. Imaging and multidisciplinary assessment follow, and treatment is cytoreductive surgery with platinum-based chemotherapy, aiming to leave no visible residual disease because residual volume strongly predicts survival.

Example 3. A 19-year-old woman has a rapidly enlarging pelvic mass with a raised alpha-fetoprotein.

Age changes the differential completely. A young woman with an ovarian mass and a raised alpha-fetoprotein has a germ cell tumour, most likely a yolk sac tumour, not an epithelial cancer.

Germ cell tumours are usually curable with fertility-sparing surgery and chemotherapy, so the outlook is far better than the presentation suggests, and preserving the contralateral ovary and uterus is an explicit goal of management.

Summary

• Name the driver: virus for cervix, unopposed oestrogen for endometrium, ovulation for ovary.
• The driver explains the screening, the presentation and the prognosis.
• Human papillomavirus E6 degrades p53 and E7 inactivates retinoblastoma protein.
• Most infections clear; cancer requires persistence over a decade or more.
• The long preinvasive window is why screening works.
• The transformation zone is the target of screening and treatment.
• Advanced cervical cancer kills by bilateral ureteric obstruction and uraemia.
• India uses visual inspection with acetic acid because it reaches the population.
• India launched single-dose human papillomavirus vaccination for girls aged 14 in February 2026.
• Vaccination does not remove the need for screening.
• FIGO 2018 allowed imaging and pathology to determine cervical stage.
• Nodal disease is stage IIIC, subdivided into pelvic and para-aortic.
• Locally advanced cervical cancer is treated with chemoradiation, not surgery.
• Every endometrial risk factor is a route to unopposed oestrogen.
• Tamoxifen is antagonist at breast and agonist at endometrium.
• Type 1 endometrial cancer is oestrogen-driven; type 2 is not and is aggressive.
• Postmenopausal bleeding is endometrial cancer until proved otherwise.
• An endometrial thickness above about 4 millimetres requires sampling.
• Atypical hyperplasia is treated by hysterectomy, not observation.
• FIGO 2023 incorporated molecular classification into endometrial staging.
• POLE-mutated tumours are downstaged; p53-abnormal tumours are upstaged.
• Mismatch repair deficiency identifies Lynch syndrome and predicts immunotherapy response.
• Incessant ovulation explains ovarian risk and protective factors.
• The combined pill is strongly protective and the effect persists for decades.
• Many high-grade serous carcinomas arise in the fallopian tube fimbria.
• Ovarian cancer presents late because the pelvis accommodates growth silently.
• Population screening for ovarian cancer does not work.
• CA-125 monitors rather than diagnoses and rises in many benign conditions.
• Residual disease volume after cytoreduction strongly predicts survival.
• Germ cell tumours occur in young women and are usually curable.
• Granulosa cell tumours secrete oestrogen; Sertoli-Leydig secrete androgens.
• Meigs syndrome is fibroma with ascites and pleural effusion.
• Krukenberg tumour is bilateral ovarian metastasis with signet ring cells.
• Cervical intraepithelial neoplasia is graded by epithelial thickness replaced.
• Grade 1 usually regresses; grades 2 and 3 are treated.
• Excision slightly raises later preterm birth risk, so over-treatment is not harmless.
• Vulvar cancer has a viral route in younger women and a lichen sclerosus route in older.
• Chronic vulvar itching must be examined and biopsied, not treated blindly.
• A complete mole is diploid, entirely paternal, with no fetal tissue.
• Very high chorionic gonadotropin can cause thyrotoxicosis and early pre-eclampsia.
• Choriocarcinoma is curable even with metastases.