21st June 2023

Gynaecological malignancies

Uterine cancer

Cancer of the uterus typically presents early due to the presence of post-menopausal or irregular menstrual bleeding, present in 90% of cases. The risk of uterine cancer increases with age, with a peak of cancers diagnosed between ages 40-74. Oestrogen has a pivotal role in the genesis of uterine malignancy as it causes the cells of the endometrium to grow and divide. Related risk factors include obesity, due to the presence of greater levels of oestrogen as a result of increased production of the enzyme aromatase, which peripherally converts circulating androgens into oestrogens. Early menarche and late menopause increase exposure to oestrogen. Hormone replacement therapy and tamoxifen are also implicated. Risk is also elevated in those with Lynch syndrome.

The primary treatment in early-stage disease is a simple hysterectomy. Vaginal vault brachytherapy, external beam radiotherapy and chemotherapy have roles to reduce the risk of recurrence. Chemotherapy, immunotherapy, and radiotherapy have a role in the management of metastatic disease as well as progesterone in the management of ER+ve disease.

Cervical cancer

Cancers of the cervix may present with abnormal vaginal bleeding, dyspareunia, vaginal discharge, pelvic pain or asymptomatically through the national screening programme. NHS screening in England is currently offered every three years between the ages 25-49 and every 5 years between the ages 50-64 to everyone with a cervix. The programme differs across the UK and so questions on the frequency of screening are unlikely to feature in the exam. High-risk HPV infection is found in association with >99% of cervical cancers and therefore is the primary test on the screening sample. HPV negative samples are not further tested. Those found to have a mild dyskaryosis will be invited for a repeat smear as the majority of these changes regress spontaneously. Those with moderate-high grade dyskaryosis will be invited for a colposcopy for diagnosis +/- treatment.

The majority of cervical cancers are squamous cell carcinoma, with adenocarcinoma accounting for 10-15% of cases. Surgical options are the mainstay of treatment for small, organ-confined tumours (<4cm). For patients with very small tumours, fertility-sparing treatments can be offered in the form of a LLETZ (large loop excision of the transformation zone) or trachelectomy. For those tumours >4cm or those which have invaded beyond the cervix, radical treatment is pursued with radical chemoradiotherapy followed by brachytherapy. The management of metastatic disease includes chemotherapy, radiotherapy, and an emerging role for immunotherapy.

Ovarian cancer

Cancers of the ovary are subdivided into the cell of origin. The majority are epithelial in origin, and this also encompasses malignancies of the Fallopian tube and peritoneum. Epithelial cancers are further subdivided into serous carcinoma, endometrioid (linked to endometriosis), clear cell (also linked to endometriosis) and mucinous. The latter should be differentiated from metastatic spread from a mucinous gastrointestinal primary and typically the appendix is resected during surgery to rule this out as a primary site.

Germ-cell tumours are less common but should be suspected in patients presenting at a young age. These can be divided into benign tumours (e.g. mature teratoma) and malignant tumours including dysgerminomas (the ovarian equivalent of seminomas), yolk sac tumours and choriocarcinomas.

Sex-cord stromal tumours are rare entities, making up 5% of ovarian cancers. They originate from the supportive structures of the ovary and can be functional, secreting excessive androgens and oestrogens. Therefore, these may present with dysfunctional menstrual bleeding, post-menopausal bleeding, and breast tenderness.

In those with suspected cancer, the Risk of Malignancy Index (RMI) is employed. This is calculated using the formula RMI = CA125 x U x M. CA125 is a serum tumour marker which is non-diagnostic but is often raised in ovarian malignancy. U confers a score based on ultrasound features, with 1 point for each of the following characteristics: multilocular cysts, solid areas, metastases, ascites, and bilateral lesions. U = 0 (for an ultrasound score of 0), U = 1 (for an ultrasound score of 1), and U = 3 (for an ultrasound score of 2 to 5). M confers the menopausal status, with a score of 1 for pre-menopausal patients and 3 for post-menopausal patients. Referral onwards for specialist review should be triggered in those patients with an RMI of 250 or more.

Treatment for ovarian cancer is typically with surgery, guided by the extent of the disease, ranging from a simple oophorectomy, to total macroscopic clearance of disseminated disease, as well as exenterative surgery. Neoadjuvant or adjuvant chemotherapy is guided by the staging and characteristics of the underlying malignancy.