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Incidence and Mortality
Estimated new cases and deaths from vaginal (and other female genital) cancer in the United States in 2012:
Carcinomas of the vagina are uncommon tumors comprising about 1% of the cancers that arise in the female genital system.[1,2]
Early stage tumors are often curable with local modality therapies, but there is no standard treatment of proven efficacy for metastatic disease. A large proportion (30%–50%) of women with vaginal carcinomas have had a prior hysterectomy for benign, pre-malignant, or malignant disease.[3,4]
The American Joint Committee on Cancer (AJCC) staging system indicates that tumors in the vagina that involve the cervix of women with an intact uterus are classified as cervical cancers. Therefore, tumors that may have actually originated in the apical vagina but extend to the cervix would be classified as cervical cancers.
Squamous cell cancer (SCC) accounts for approximately 85% of vaginal cancer cases. SCC initially spreads superficially within the vaginal wall and later invades the paravaginal tissues and the parametria. Distant hematogenous metastases occur most commonly in the lungs, and less frequently in liver, bone, or other sites. SCC of the vagina is associated with a high rate of infection with oncogenic strains of human papillomavirus (HPV) and has many risk factors in common with SCC of the cervix.[6,7,8] HPV infection has also been described in a case of vaginal adenocarcinoma.
Approximately 5% to 10% of cases of vaginal cancers are adenocarcinomas. A rare form of adenocarcinoma (clear cell carcinoma, described below) occurs in association with in utero exposure to diethylstilbestrol (DES), with a peak incidence at young ages (less than 30 years). However, adenocarcinomas that are not associated with DES exposure occur primarily during postmenopausal years.
The association between the clear cell carcinomas and in utero exposure to DES was first reported in 1971. The incidence of this disease, which is highest for those exposed during the first trimester, peaked in the mid-1970s, reflecting the use of DES in the 1950s. It is extremely rare now. However, women with a known history of in utero DES exposure should be carefully followed for this tumor.
Vaginal adenosis is most commonly found in young women who had in utero exposure to DES and may coexist with a clear cell adenocarcinoma, though it rarely progresses to adenocarcinoma. Adenosis is replaced by squamous metaplasia, which occurs naturally, and requires follow-up but not removal.
Rarely, melanomas (often nonpigmented), sarcomas, or small-cell carcinomas have been described as primary vaginal cancers.
Patient prognosis depends primarily on the stage of disease, but survival is reduced among those who are older than 60 years, are symptomatic at the time of diagnosis, have lesions of the middle and lower third of the vagina, or have poorly differentiated tumors.
In addition, the length of vaginal wall involvement has been found to be associated with survival and stage of disease in vaginal SCC patients.
Non–DES-associated adenocarcinomas generally have a worse prognosis than SCC tumors, but DES-associated clear cell tumors have a relatively good prognosis. The natural history, prognosis, and treatment of other primary vaginal cancers (i.e., sarcoma, melanoma, lymphoma, and carcinoid tumors) are different and are not covered in this summary.
Therapeutic options depend on tumor stage; surgery and radiation therapy are highly effective in early stages, whereas radiation therapy is the primary treatment of more advanced stages. Chemotherapy has not been shown to be curative for advanced vaginal cancer, and there are no standard drug regimens.
If the cervix is intact, biopsies are mandatory to rule out a primary carcinoma of the cervix. Carcinoma of the vulva should also be ruled out.
The Féderation Internationale de Gynécologie et d'Obstétrique (FIGO) and the American Joint Committee on Cancer (AJCC) have designated staging to define vaginal cancer; the FIGO system is most commonly used.[1,2] The definitions of the AJCC's T, N, and M categories correspond to the stages accepted by FIGO.
FIGO staging system (and modified World Health Organization [WHO] prognostic scoring system)
The FIGO staging system is as follows:
In addition, the FIGO staging system incorporates a modified WHO prognostic scoring system. The scores from the eight risk factors are summed and incorporated into the FIGO stage, separated by a colon (e.g., Stage II:4, Stage IV:9, etc.). Unfortunately, a variety of risk scoring systems have been published, making comparisons of results difficult.
Roles of Radiation, Surgery, and Chemotherapy
Given the rarity of vaginal carcinoma, studies are limited to retrospective case series that may span a number of years, usually from single-referral institutions.[Level of evidence 3iiiD] Comparison of different treatment approaches is further complicated by the frequent failure of investigators to provide precise staging criteria (particularly for stage I vs. stage II disease) or criteria for the choice of treatment modality. This has led to a broad range of reported disease control and survival rates for any given stage and treatment modality. In addition, given the long time span covered by these case series, there are often changes within a given case series in the available staging tests and radiation techniques, including the shift to high-energy accelerators and conformal- and intensity-modulated radiation.[2,3]
Factors to be considered in planning therapy for vaginal cancer include:
In a series of 100 women studied retrospectively over 30 years, 50% had undergone hysterectomy prior to the diagnosis of vaginal cancer. In this posthysterectomy group, 31 of 50 (62%) women developed cancers limited to the upper third of the vagina. In women who had not previously undergone hysterectomy, upper vaginal lesions were found in only 17 of 50 (34%) women.
The lymphatics may drain to pelvic or inguinal nodes or both, depending on tumor location, and consideration should be given to these areas in treatment planning.
Radiation-induced damage to nearby organs may include:[2,3]
The proximity of the vagina to the bladder or rectum also limits surgical treatment options and increases short- and long-term surgical complications and functional deficits involving these organs.
For patients with carcinoma of the vagina in its early stages, radiation or surgery or a combination of these treatments are standard treatment. Data from randomized trials are lacking and the choice of therapy is generally determined by institutional experience and the factors listed above. For patients with stages III and IVA disease, radiation therapy is standard and includes external-beam radiation, alone or with brachytherapy. Regional lymph nodes are included in the radiation portal. When used alone, external-beam radiation involves a 60 Gy to 70 Gy tumor dose, using shrinking fields, delivered within 6 to 7 weeks. Intracavitary brachytherapy provides insufficient dose penetration for locally advanced tumors, so interstitial brachytherapy (75 Gy–85 Gy) is used if brachytherapy is employed.[1,5]
Local control is a problem with bulky tumors. In recent years, some investigators have also used concurrent chemotherapy with agents such as cisplatin, bleomycin, mitomycin-C, floxuridine, and vincristine; but this practice has not been proven to improve outcomes. It is an extrapolation from treatment approaches used in cervical cancer, based on shared etiologic and risk factors.
For patients with stage IVB or recurrent disease that cannot be managed with local treatments, current therapy is inadequate. No established anticancer drugs can be considered of proven clinical benefit, although patients are often treated with regimens used to treat cervical cancer. (Refer to the PDQ summary on Cervical Cancer Treatment for more information.)
Concurrent chemotherapy, using 5-fluorouracil or cisplatin-based therapy, and radiation are sometimes advocated, again based solely on extrapolation from cervical cancer management strategies.[6,7,8] Experience is limited to small case series and the incremental impact on survival and local control is not well defined.[Level of evidence 3iiiDiv] Because of the rarity of these patients, they should be considered candidates for clinical trials of anticancer drugs and/or radiosensitizers to attempt to improve survival or local control.
Management of the extremely rare vaginal clear cell carcinoma is generally similar to the management of squamous cell carcinoma, though techniques that preserve vaginal and ovarian function are given strong consideration in treatment planning, given the young average age at diagnosis.
In light of the many uncertainties about the relative efficacy of treatment approaches, ongoing clinical trials should be discussed with patients if they are eligible. Information about ongoing clinical trials is available from the NCI Web site.
As is the case with other gynecologic malignancies, the evidence base for surveillance after initial management of vaginal cancer is weak because of a lack of randomized, or even prospective, clinical studies. There is no reliable evidence that routine cytologic or imaging procedures in patients improve health outcomes beyond what is achieved by careful physical examination and assessment of new symptoms. Therefore, outside the investigational setting, imaging procedures may be reserved for patients in whom physical examination or symptoms raise clinical suspicion of a recurrence or progression.
Vaginal Intraepithelial Neoplasia (VAIN) Including Squamous Cell CarcinomaIn Situ
Squamous cell carcinoma in situ of the vagina is a lesion that falls within the more general category known as vaginal intraepithelial neoplasia (VAIN). VAIN, the presence of noninvasive squamous cell atypia, is associated with a high rate of human papillomavirus (HPV) infection and is thought to have a similar etiology as cervical intraepithelial neoplasia (CIN).[1,2,3] VAIN is classified by the degree of involvement of the epithelium: VAIN 1, 2, and 3 denote involvement of the upper one-third, two-thirds, and more than two-thirds of the epithelial thickness, respectively. Carcinoma in situ denotes VAIN 3 lesions that involve the full thickness of the epithelium. The FIGO staging system no longer includes vaginal carcinoma in situ (Stage 0) in its staging system, but it is retained in the AJCC staging system. Vaginal carcinoma in situ is often multifocal and commonly occurs at the vaginal vault. Because it is associated with other genital neoplasia, and in some cases may be an extension of CIN, the cervix (when present) and vulva should be carefully evaluated.
Women with VAIN 1 can usually be observed carefully without ablative or surgical treatment, since the lesions often regress spontaneously. The natural history of VAIN is not known with precision because of its rarity, but patients with VAIN 3 are felt to be at substantial risk of progression to invasive cancer and are treated immediately. The intermediate grade, VAIN 2, is variously managed by careful observation or initial treatment. The treatments listed below have not been compared directly in randomized trials, so their relative efficacy is uncertain.[Level of evidence 3iiiDiv] The selection of treatment depends on patient factors, anatomic location, evidence of multifocality, and local expertise (e.g., anatomical distortion of the vaginal vault related to wall closure at the time of prior hysterectomy requires excision for technical reasons to exclude the possibility of invasion by buried disease). Lesions with hyperkeratosis respond better to excision or laser vaporization than to fluorouracil.
Standard treatment options:
Imiquimod cream 5%, an immune stimulant used to treat genital warts, is an additional topical therapy that has a reported complete clinical response rate of 50% to 86% in small case series of patients with multifocal high-grade HPV-associated VAIN 2 and 3. However, it is investigational, and it may have only short-lived efficacy.
Current Clinical Trials
Check for U.S. clinical trials from NCI's list of cancer clinical trials that are now accepting patients with stage 0 vaginal cancer. The list of clinical trials can be further narrowed by location, drug, intervention, and other criteria.
General information about clinical trials is also available from the NCI Web site.
The treatments listed below have not been directly compared in randomized trials.[Level of evidence 3iiiD] Because of differences in patient selection, local expertise, and staging criteria, it is difficult to determine whether there are differences in disease control rates.
Squamous Cell Carcinoma
Standard treatment options for superficial lesions less than 0.5 cm thick:
Standard treatment options for lesions greater than 0.5 cm thick:
Check for U.S. clinical trials from NCI's list of cancer clinical trials that are now accepting patients with stage I vaginal cancer. The list of clinical trials can be further narrowed by location, drug, intervention, and other criteria.
The treatments listed below have not been directly compared in randomized trials.[Level of evidence 3iiiD] As a result of differences in patient selection, local expertise, and staging criteria, it is difficult to determine whether there are differences in disease control rates. Radiation therapy is the most common treatment for patients with stage II vaginal cancer.
Standard treatment options:
Check for U.S. clinical trials from NCI's list of cancer clinical trials that are now accepting patients with stage II vaginal cancer. The list of clinical trials can be further narrowed by location, drug, intervention, and other criteria.
Check for U.S. clinical trials from NCI's list of cancer clinical trials that are now accepting patients with stage III vaginal cancer. The list of clinical trials can be further narrowed by location, drug, intervention, and other criteria.
Check for U.S. clinical trials from NCI's list of cancer clinical trials that are now accepting patients with stage IVA vaginal cancer. The list of clinical trials can be further narrowed by location, drug, intervention, and other criteria.
Current therapy is of unclear benefit for patients with Stage IVB disease. No established anticancer drugs can be considered of proven clinical benefit, although patients are often treated with regimens used to treat cervical cancer. (Refer to the PDQ summary on Cervical Cancer Treatment for more information.)
Concurrent chemotherapy using 5-fluorouracil or cisplatin-based therapy and radiation is sometimes advocated, and, again, this is based solely on extrapolation from cervical cancer management strategies.[1,2,3] Experience is limited to small case series and the incremental impact on survival and local control is not well defined.[Level of evidence 3iiiDiv] Considering the rarity of these patients, they should be considered candidates for clinical trials to improve survival or local control. Information about ongoing clinical trials is available from the NCI Web site.
Check for U.S. clinical trials from NCI's list of cancer clinical trials that are now accepting patients with stage IVB vaginal cancer. The list of clinical trials can be further narrowed by location, drug, intervention, and other criteria.
Recurrence carries a grave prognosis. In a large series, only five of fifty patients with recurrence were salvaged by surgery or radiation therapy. All five of these salvaged patients originally presented with stage I or II disease and had tumor recurrence in the central pelvis. Most recurrences occur in the first 2 years after treatment. In centrally recurrent vaginal cancers, some patients may be candidates for pelvic exenteration or radiation therapy.
No established anticancer drugs can be considered of proven clinical benefit, although patients are often treated with regimens used to treat cervical cancer. (Refer to the PDQ summary on Cervical Cancer Treatment for more information.) If eligible, patients should be offered the option of participation in one of the ongoing clinical trials. Information about ongoing clinical trials is available from the NCI Web site.
Check for U.S. clinical trials from NCI's list of cancer clinical trials that are now accepting patients with recurrent vaginal cancer. The list of clinical trials can be further narrowed by location, drug, intervention, and other criteria.
The PDQ cancer information summaries are reviewed regularly and updated as new information becomes available. This section describes the latest changes made to this summary as of the date above.
This summary was comprehensively reviewed and extensively revised.
This summary is written and maintained by the PDQ Adult Treatment Editorial Board, which is editorially independent of NCI. The summary reflects an independent review of the literature and does not represent a policy statement of NCI or NIH. More information about summary policies and the role of the PDQ Editorial Boards in maintaining the PDQ summaries can be found on the About This PDQ Summary and PDQ NCI's Comprehensive Cancer Database pages.
Purpose of This Summary
This PDQ cancer information summary for health professionals provides comprehensive, peer-reviewed, evidence-based information about the treatment of vaginal cancer. It is intended as a resource to inform and assist clinicians who care for cancer patients. It does not provide formal guidelines or recommendations for making health care decisions.
Reviewers and Updates
This summary is reviewed regularly and updated as necessary by the PDQ Adult Treatment Editorial Board, which is editorially independent of the National Cancer Institute (NCI). The summary reflects an independent review of the literature and does not represent a policy statement of NCI or the National Institutes of Health (NIH).
Board members review recently published articles each month to determine whether an article should:
Changes to the summaries are made through a consensus process in which Board members evaluate the strength of the evidence in the published articles and determine how the article should be included in the summary.
The lead reviewers for Vaginal Cancer Treatment are:
Any comments or questions about the summary content should be submitted to Cancer.gov through the Web site's Contact Form. Do not contact the individual Board Members with questions or comments about the summaries. Board members will not respond to individual inquiries.
Levels of Evidence
Some of the reference citations in this summary are accompanied by a level-of-evidence designation. These designations are intended to help readers assess the strength of the evidence supporting the use of specific interventions or approaches. The PDQ Adult Treatment Editorial Board uses a formal evidence ranking system in developing its level-of-evidence designations.
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National Cancer Institute: PDQ® Vaginal Cancer Treatment. Bethesda, MD: National Cancer Institute. Date last modified <MM/DD/YYYY>. Available at: http://cancer.gov/cancertopics/pdq/treatment/vaginal/HealthProfessional. Accessed <MM/DD/YYYY>.
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Last Revised: 2012-09-07
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