Vaginal cancer

Overview

• Rare: ~1 to 2% of gynecologic cancers. Most are squamous cell carcinoma, typically in the sixth to seventh decade; incidence before age 40 is rising with HPV.
• Consider metastatic/recurrent disease first: a new vaginal lesion is more often metastatic or recurrent from another site (cervix, vulva, ovary, breast, endometrium, uterus) than a true primary vaginal carcinoma.
• Histology: squamous cell (~85%, HPV-related); adenocarcinoma (clear cell, from in-utero DES exposure); mucosal melanoma; sarcoma (sarcoma botryoides in children); small cell. Non-squamous types are extremely rare.
• Risk factors: HPV (16, 18), smoking, early age at first intercourse, multiple partners, prior STDs, prior cervical/vulvar HPV-related disease, prior pelvic RT, in-utero DES exposure (clear cell).

Workup and staging

• Pelvic exam, biopsy, exam under anesthesia.
• Imaging: pelvic MRI, CT chest, PET-CT.
• FIGO staging: stage I (vaginal wall only) through stage IVA (invasion of bladder/rectal mucosa or extension beyond the true pelvis) and IVB (distant metastasis); note stage II = subvaginal tissue not reaching the pelvic wall, stage III = extends to pelvic wall.

Treatment

• No prospective trials guide treatment; recommendations extrapolate from cervical cancer and retrospective vaginal series.
• Primary treatment is surgical when feasible (e.g., partial vaginectomy for small stage I), or RT (brachytherapy with or without EBRT).
• Stage II to IVA: definitive concurrent chemoRT (cisplatin + EBRT + brachytherapy boost), extrapolated from cervical standard of care. No prospective data prove chemoRT superior to RT alone, but many extrapolate from cervical randomized trials.
• Stage IVB / metastatic / recurrent: platinum-based chemo plus pembrolizumab for PD-L1-positive disease (CPS ≥1), with or without bevacizumab (cervix-extrapolated, KEYNOTE-826); tisotumab vedotin is NCCN-listed for vaginal SCC. Palliative cytotoxic chemo may be offered, though no prospective data establish active agents.
• Mucosal melanoma: different biology; localized resectable disease: wide local excision with negative margins (consider perioperative checkpoint inhibitor); unresectable or metastatic: nivolumab + ipilimumab or anti-PD-1 monotherapy.

Survivorship

• Follow with serial physical and pelvic examinations on a schedule similar to cervical cancer.

High-yield vaginal pearls

• HPV-related SCC is most common; rule out metastasis from another primary first.
• Clear cell adenocarcinoma from in-utero DES exposure.
• ChemoRT is the mainstay for invasive locally advanced disease.
• Mucosal melanoma has different biology; for localized, resectable disease, surgical excision with negative margins is the primary local treatment, with checkpoint immunotherapy for unresectable/metastatic or perioperative settings.