Vaginal Cancer: Patient Guide

Primary vaginal cancer starts in the vagina itself. NCI's PDQ summary puts it at roughly 2% of cancers of the female genital system, which makes it one of the least common gynecologic cancers.

The word primary is doing real work in that sentence. Cancer found in the vagina is far more often a spread from the cervix, the uterus, or the vulva. PDQ is explicit on this point. A biopsy is required to rule out a cervical or vulvar origin. Only then can a tumor be called a vaginal primary.

PDQ gives the breakdown.

• Squamous cell carcinoma: 80% to 90% of cases. It arises from the flat cells lining the vagina.
• Adenocarcinoma: 5% to 10%. It arises from gland cells.
• Rare types: melanoma, sarcoma, small cell carcinoma, lymphoma, and carcinoid tumors.

Squamous and adenocarcinoma are treated differently at early stage, so the pathology line at the top of the report changes the plan.

PDQ names four risk patterns, and they do not overlap much.

HPV. Human papillomavirus is strongly associated with squamous cell carcinoma here. PDQ notes it shares causal factors with cervical cancer.

DES exposure before birth. Diethylstilbestrol was a drug given to pregnant women decades ago. Exposure in the womb causes clear cell adenocarcinoma of the vagina. Risk is highest when exposure fell in the first trimester. PDQ notes this peaked in the 1970s and is now extremely rare.

Prior hysterectomy. In one 30-year series PDQ cites, 50% of patients had undergone a hysterectomy before their vaginal cancer diagnosis.

Age. Being older than 60 is listed among the poor prognostic factors.

PDQ lists six symptoms. They are abnormal vaginal bleeding, painful intercourse, and pelvic pain. The others are a vaginal mass, painful urination, and constipation.

Here is where the risk factors and the screening rules collide. The U.S. Preventive Services Task Force advises against cervical cancer screening after one specific surgery. That is a hysterectomy in which the cervix was removed. The advice applies only when there is no history of a high-grade precancerous lesion or cervical cancer. That is a Grade D recommendation, meaning the harms outweigh the benefits.

That guidance is about cervical cancer, and it is correct: there is no cervix left to screen. But PDQ lists prior hysterectomy as a risk factor for vaginal cancer. So a woman can be correctly told she no longer needs Pap tests and still develop a cancer in the remaining vaginal tissue.

The practical rule that follows: do not wait for a screening test to catch this. Ask for a pelvic exam and biopsy, not observation, for any of these:

• vaginal bleeding after menopause.
• bleeding after intercourse.
• a lump or mass you can feel in the vagina.
• pelvic pain that is new and unexplained.
• a vaginal symptom that has not resolved after treatment for an assumed infection.

PDQ describes pelvic examination, cervical cytology, HPV testing, and colposcopy, which uses a lighted magnifying instrument to inspect the tissue.

Biopsy is mandatory. Cytology alone cannot make this diagnosis, and it cannot establish that the tumor started in the vagina rather than somewhere adjacent.

• Stage I: limited to the vaginal wall.
• Stage II: involves the tissue beneath the vagina but has not reached the pelvic wall.
• Stage III: extends to the pelvic wall.
• Stage IVa: invades the bladder or rectum, or extends beyond the pelvis.
• Stage IVb: distant spread. PDQ notes the lungs are the most common site.

Stage is not the only thing that predicts outcome. PDQ lists five poor prognostic factors. Age over 60 is one. Having symptoms at presentation is another. So is a lesion in the middle or lower third of the vagina. The last two are poorly differentiated tumor cells and wide involvement of the vaginal wall.

Vaginal intraepithelial neoplasia, or VaIN, is abnormal cells confined to the surface lining. It is not invasive cancer.

PDQ lists several approaches. They are laser therapy, wide local excision, and vaginectomy. Topical fluorouracil cream, intracavitary radiation, and imiquimod cream are also options. For imiquimod, PDQ cites response rates of 50% to 86% in case series.

Case series are weaker evidence than randomized trials. That is worth knowing when several options are presented as equivalent.

Stage I squamous cell carcinoma. For superficial lesions under 0.5 cm thick, PDQ describes intracavitary brachytherapy alone, external beam radiation, or wide local excision. Brachytherapy places the radiation source inside the body, close to the tumor. Thicker lesions get more. One option is radical vaginectomy with pelvic lymph node removal. The other is external beam radiation plus brachytherapy, to 75 Gy or more. Gy stands for gray, the unit of radiation dose.

Stage I adenocarcinoma. PDQ describes total radical vaginectomy with hysterectomy and lymph node removal. Which nodes are removed depends on location: pelvic nodes for upper vaginal disease, inguinal nodes in the groin for lower vaginal disease. Radiation is added for positive margins.

Stages II through IVa. Radiation is standard. PDQ describes external beam radiation, alone or with interstitial or intracavitary brachytherapy. The dose is 75 to 80 Gy at the tumor. The lateral pelvic wall gets 55 to 60 Gy. For lesions in the lower third, the groin nodes receive an elective dose of 45 to 50 Gy. Radical vaginectomy, pelvic exenteration, and chemoradiation are alternatives, though PDQ notes the evidence base is limited.

Stage IVb. Treatment is palliative radiation with or without chemotherapy. PDQ is candid that current therapy is inadequate. Cisplatin- or fluorouracil-based chemoradiation is borrowed from cervical cancer protocols. Strong evidence in this disease is lacking.

Recurrence. Prognosis is poor. In one large series PDQ cites, salvage succeeded in only 10% of cases. Those were all central recurrences, treated with pelvic exenteration or radiation.

Radiation injury to nearby organs. PDQ names rectovaginal and vesicovaginal fistulas. Those are abnormal openings between the vagina and the rectum or bladder. Strictures and tissue death are also listed. Ask what is being done to limit dose to the bladder and rectum, and what symptoms should prompt an urgent call.

DPYD testing before fluorouracil. DPYD is the gene for the enzyme that clears fluoropyrimidine chemotherapy. People with certain variants clear it poorly and can suffer severe toxicity. PDQ puts the cost of the test under $200, and notes that insurance coverage varies. Depending on the genotype, avoiding fluoropyrimidines or halving the dose may be recommended. PDQ also names a trade-off: testing may delay therapy by two weeks, which would not be advisable in an urgent situation. Ask whether it was ordered.

For younger patients, PDQ favors techniques that spare vaginal and ovarian function where possible. That applies above all in clear cell adenocarcinoma.

HPV vaccination is the lever that exists. CDC recommends 2 doses at ages 11 to 12. Catch-up vaccination runs through age 26. Adults aged 27 through 45 may decide to get it after discussion with a clinician.

Dose counts depend on age at the first dose. A first dose before the 15th birthday means 2 doses, given 6 to 12 months apart. A first dose at 15 through 26 means 3 doses over 6 months. People who are immunocompromised, ages 9 through 26, get 3 doses.

• Call 911 or go to an emergency department if vaginal bleeding soaks a pad every hour or two, or if bleeding leaves you faint, breathless, or cold and clammy.
• Call your cancer team straight away, at any hour, if you are on chemotherapy or chemoradiation and your temperature reaches 100.4°F (38°C). CDC calls a fever during chemotherapy a medical emergency, because treatment can leave too few white cells to contain an infection. If you cannot reach your team, go to an emergency department and tell staff you are having chemotherapy.
• Call 911 or go to an emergency department if urine or stool starts passing through the vagina, or you cannot pass urine at all. A fistula or a blocked bladder after radiation needs seeing straight away.
• Call your care team the same day if pelvic pain becomes severe, discharge turns foul-smelling, or bleeding is new and will not settle.
• Call your care team within a day or two if you have new burning on urination, ongoing constipation, or a lump you can feel that was not there before.

• https://www.cancer.gov/types/vaginal/hp/vaginal-treatment-pdq
• https://www.cdc.gov/cancer-preventing-infections/patients/fever.html
• https://www.uspreventiveservicestaskforce.org/uspstf/recommendation/cervical-cancer-screening
• https://www.cdc.gov/hpv/vaccines/index.html