Note: Estimated new cases and deaths from vaginal (and other female genital) cancer in the United States in 2007: [1]
• New cases: 2,140.
• Deaths: 790.
Carcinomas of the vagina are uncommon tumors comprising 1% to 2% of gynecologic malignancies. They can be effectively treated, and when found in early stages, are often curable. The histologic distinction between squamous cell carcinoma and adenocarcinoma is important because the two types represent distinct diseases, each with a different pathogenesis and natural history. Squamous cell vaginal cancer (approximately 85% of cases) initially spreads superficially within the vaginal wall and later invades the paravaginal tissues and the parametria. Distant metastases occur most commonly in the lungs and liver. [2] Adenocarcinoma (approximately 15% of cases) has a peak incidence between 17 and 21 years of age and differs from squamous cell carcinoma by an increase in pulmonary metastases and supraclavicular and pelvic node involvement. [3] Rarely, melanoma and sarcoma are described as primary vaginal cancers. Adenosquamous carcinoma is a rare and aggressive mixed epithelial tumor comprising approximately 1% to 2% of cases.
Prognosis depends primarily on the stage of disease, but survival is reduced in patients who are greater than 60 years of age, are symptomatic at the time of diagnosis, have lesions of the middle and lower third of the vagina, or have poorly differentiated tumors. [4] [5] In addition, the length of vaginal wall involvement has been found to be significantly correlated to survival and stage of disease in squamous cell carcinoma patients. [6]
Therapeutic alternatives depend on stage; surgery or radiation therapy is highly effective in early stages, while radiation therapy is the primary treatment of more advanced stages. [7] [8] Chemotherapy has not been shown to be curative for advanced vaginal cancer, and there are no standard drug regimens.
Clear cell adenocarcinomas are rare and occur most often in patients less than 30 years of age who have a history of in utero exposure to diethylstilbestrol (DES). 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. [3] Young women with a history of in utero DES exposure should prospectively be followed carefully to diagnose this disease at an early stage. In women who have been carefully followed and well-managed, the disease is highly curable.
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. The natural history, prognosis, and treatment of other primary vaginal cancers (sarcoma, melanoma, lymphoma, and carcinoid tumors) may be different, and specific references should be sought. [9]
References:
1. American Cancer Society.: Cancer Facts and Figures 2007. Atlanta, Ga: American Cancer Society, 2007. Also available online. Last accessed December 20, 2007.
2. Gallup DG, Talledo OE, Shah KJ, et al.: Invasive squamous cell carcinoma of the vagina: a 14-year study. Obstet Gynecol 69 (5): 782-5, 1987.
3. Herbst AL, Robboy SJ, Scully RE, et al.: Clear-cell adenocarcinoma of the vagina and cervix in girls: analysis of 170 registry cases. Am J Obstet Gynecol 119 (5): 713-24, 1974.
4. Kucera H, Vavra N: Radiation management of primary carcinoma of the vagina: clinical and histopathological variables associated with survival. Gynecol Oncol 40 (1): 12-6, 1991.
5. Eddy GL, Marks RD Jr, Miller MC 3rd, et al.: Primary invasive vaginal carcinoma. Am J Obstet Gynecol 165 (2): 292-6; discussion 296-8, 1991.
6. Dixit S, Singhal S, Baboo HA: Squamous cell carcinoma of the vagina: a review of 70 cases. Gynecol Oncol 48 (1): 80-7, 1993.
7. Perez CA, Camel HM, Galakatos AE, et al.: Definitive irradiation in carcinoma of the vagina: long-term evaluation of results. Int J Radiat Oncol Biol Phys 15 (6): 1283-90, 1988.
8. Pride GL, Schultz AE, Chuprevich TW, et al.: Primary invasive squamous carcinoma of the vagina. Obstet Gynecol 53 (2): 218-25, 1979.
9. Sulak P, Barnhill D, Heller P, et al.: Nonsquamous cancer of the vagina. Gynecol Oncol 29 (3): 309-20, 1988.
Stage Information
Cervical biopsies are mandatory to rule out carcinoma of the cervix. Carcinoma of the vulva should also be ruled out.
Stages are defined by the Federation Internationale de Gynecologie et d’Obstetrique (FIGO) and the American Joint Committee on Cancer’s (AJCC) TNM classification. [1] The definitions of the T categories correspond to the stages accepted by the FIGO and both systems are included for comparison.
TNM Definitions
TNM Categories/FIGO Stages
Primary tumor (T)
• TX: Primary tumor cannot be assessed
• T0: No evidence of primary tumor
• Tis/ 0: Carcinoma in situ
• T1/I: Tumor confined to vagina
• T2/II: Tumor invades paravaginal tissues but not to pelvic wall*
• T3/III: Tumor extends to pelvic wall*
• T4/IVA: Tumor invades mucosa of the bladder or rectum and/or extends beyond the true pelvis (Bullous edema is not sufficient evidence to classify a tumor as T4.)
*Pelvic wall is defined as muscle, facia, neurovascular structures, or skeletal portions of the bony pelvis.
Regional lymph nodes (N)
• NX: Regional nodes cannot be assessed
• N0: No regional lymph node metastasis
• N1/IVB: Pelvic or inguinal lymph node metastasis
Distant metastasis (M)
• MX: Distant metastasis cannot be assessed
• M0: No distant metastasis
• M1/IVB: Distant metastasis
AJCC Stage Groupings
Stage 0
• Tis, N0, M0
Stage I
• T1, N0, M0
Stage II
• T2, N0, M0
Stage III
• T1, N1, M0
• T2, N1, M0
• T3, N0, M0
• T3, N1, M0
Stage IVA
• T4, any N, M0
Stage IVB
• Any T, any N, M1
References:
1. Vagina. In: American Joint Committee on Cancer.: AJCC Cancer Staging Manual. 6th ed. New York, NY: Springer, 2002, pp 251-257.
Treatment Option Overview
Factors to be considered in planning therapy for vaginal cancer are:
• Stage, size, and location of the lesion.
• Presence or absence of the uterus.
• Whether there has been prior pelvic radiation therapy.
In a large series of women studied retrospectively for 30 years, 50% had undergone hysterectomy prior to the diagnosis of vaginal cancer. [1] 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. The proximity of the vagina to the bladder or rectum limits treatment options and increases complications involving these organs. For patients with carcinoma of the vagina in its early stages, standard treatment applied by gynecologic oncologists or radiation oncologists is highly effective. For patients with stages III and IVA disease, radiation therapy alone is standard. For patients with stage IVB disease, current therapy is inadequate, and no established anticancer drugs can be considered standard treatment. Considering the rarity of such patients, they should be considered candidates for clinical trials using anticancer drugs and/or radiosensitizers to attempt to improve survival or local control.
Information about ongoing clinical trials is available from the NCI Web site.
References:
1. Stock RG, Chen AS, Seski J: A 30-year experience in the management of primary carcinoma of the vagina: analysis of prognostic factors and treatment modalities. Gynecol Oncol 56 (1): 45-52, 1995.
Stage 0 Vaginal Cancer
Squamous Cell Carcinoma In Situ
This disease is usually multifocal and commonly occurs at the vaginal vault. Because vaginal intraepithelial neoplasia (VAIN) is associated with other genital neoplasias, the cervix (when present) and vulva should be carefully examined. The treatments listed below produce equivalent cure rates. The selection of treatment depends on patient factors and local expertise (e.g., anatomical distortion of the vaginal vault [related to wall closure at the time of 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. [1]
Standard treatment options:
1. Wide local excision with or without skin grafting.
2. Partial or total vaginectomy with skin grafting for multifocal or extensive disease.
3. Intravaginal chemotherapy with 5% fluorouracil cream. Instillation of 1.5 g weekly for 10 weeks has been found to be as effective as more frequent use. [2]
4. Laser therapy. [2]
5. Intracavitary radiation therapy delivering 60 Gy to 70 Gy to the mucosa. [3] [4] The entire vaginal mucosa should be treated. [5]
References:
1. Wright VC, Chapman W: Intraepithelial neoplasia of the lower female genital tract: etiology, investigation, and management. Semin Surg Oncol 8 (4): 180-90, 1992 Jul-Aug.
2. Krebs HB: Treatment of vaginal intraepithelial neoplasia with laser and topical 5-fluorouracil. Obstet Gynecol 73 (4): 657-60, 1989.
3. Perez CA, Camel HM, Galakatos AE, et al.: Definitive irradiation in carcinoma of the vagina: long-term evaluation of results. Int J Radiat Oncol Biol Phys 15 (6): 1283-90, 1988.
4. Woodman CB, Mould JJ, Jordan JA: Radiotherapy in the management of vaginal intraepithelial neoplasia after hysterectomy. Br J Obstet Gynaecol 95 (10): 976-9, 1988.
5. Perez CA, Garipagaoglu M: Vagina. In: Perez CA, Brady LW, eds.: Principles and Practice of Radiation Oncology. 3rd ed. Philadelphia, Pa: Lippincott-Raven Publishers, 1998, pp 1891-1914.
Stage I Vaginal Cancer
Squamous Cell Carcinoma
The treatments listed below produce equivalent cure rates. The selection of treatment depends on patient factors and local expertise.
Standard treatment options for superficial lesions less than 0.5 cm thick:
1. Intracavitary radiation therapy. In most instances, 60 Gy to 70 Gy prescribed to 0.5 cm is delivered to the tumor for 5 to 7 days (external-beam radiation therapy [EBRT] is required for bulky lesions). [1] For lesions of the lower third of the vagina, elective radiation therapy of 45 Gy to 50 Gy is given to pelvic and/or inguinal lymph nodes. [1]
2. Surgery. Wide local excision or total vaginectomy with vaginal reconstruction, especially in lesions of the upper vagina. In cases with close or positive surgical margins, adjuvant radiation therapy should be considered. [2]
Standard treatment options for lesions greater than 0.5 cm thick:
1. Surgery. In lesions of the upper third of the vagina, radical vaginectomy and pelvic lymphadenectomy should be performed. Construction of a neovagina may be performed if feasible and if desired by the patient. [2] [3] In lesions of the lower third, inguinal lymphadenectomy should be performed. In cases with close or positive surgical margins, adjuvant radiation therapy should be considered. [2]
2. Radiation therapy. Combination of interstitial (single-plane implant) and intracavitary therapy to a dose of at least 75 Gy to the primary tumor. In addition to brachytherapy, EBRT is advocated for poorly differentiated or infiltrating tumors that may have a higher probability of lymph node metastasis. [1] [4] For lesions of the lower third of the vagina, elective radiation therapy of 45 Gy to 50 Gy is given to the pelvic and/or inguinal lymph nodes. [1]
Adenocarcinoma
Standard treatment options:
1. Surgery. Because the tumor spreads subepithelially, total radical vaginectomy and hysterectomy with lymph node dissection are indicated. The deep pelvic nodes are dissected if the lesion invades the upper vagina, and the inguinal nodes are removed if the lesion originates in the lower vagina. Construction of a neovagina may be performed if feasible and if desired by the patient. [2] In cases with close or positive surgical margins, adjuvant radiation therapy should be considered. [2] [3]
2. Intracavitary and interstitial radiation as previously described for squamous cell cancer. [1] For lesions of the lower third of the vagina, elective radiation therapy of 45 Gy to 50 Gy is given to the pelvic and/or inguinal lymph nodes. [1]
3. Combined local therapy in selected cases, which may include wide local excision, lymph node sampling, and interstitial therapy. [5]
References:
1. Perez CA, Camel HM, Galakatos AE, et al.: Definitive irradiation in carcinoma of the vagina: long-term evaluation of results. Int J Radiat Oncol Biol Phys 15 (6): 1283-90, 1988.
2. Stock RG, Chen AS, Seski J: A 30-year experience in the management of primary carcinoma of the vagina: analysis of prognostic factors and treatment modalities. Gynecol Oncol 56 (1): 45-52, 1995.
3. Rubin SC, Young J, Mikuta JJ: Squamous carcinoma of the vagina: treatment, complications, and long-term follow-up. Gynecol Oncol 20 (3): 346-53, 1985.
4. Andersen ES: Primary carcinoma of the vagina: a study of 29 cases. Gynecol Oncol 33 (3): 317-20, 1989.
5. Senekjian EK, Frey KW, Anderson D, et al.: Local therapy in stage I clear cell adenocarcinoma of the vagina. Cancer 60 (6): 1319-24, 1987.
Stage II Vaginal Cancer
Squamous Cell Carcinoma
Radiation therapy is the standard treatment for patients with stage II vaginal carcinoma.
Standard treatment options:
1. Combination of brachytherapy and external-beam radiation therapy (EBRT) to deliver a combined dose of 70 Gy to 80 Gy to the primary tumor volume. [1] For lesions of the lower third of the vagina, elective radiation therapy of 45 Gy to 50 Gy is given to the pelvic and/or inguinal lymph nodes. [1] [2]
2. Radical surgery (radical vaginectomy or pelvic exenteration) with or without radiation therapy. [3] [4]
Adenocarcinoma
Standard treatment options:
1. Combination of brachytherapy and EBRT to deliver a combined dose of 70 Gy to 80 Gy to the primary tumor. [1] For lesions of the lower third of the vagina, elective radiation therapy of 45 Gy to 50 Gy is given to the pelvic and/or inguinal lymph nodes. [1] [2]
2. Radical surgery (radical vaginectomy or pelvic exenteration) with or without radiation therapy.
References:
1. Perez CA, Camel HM, Galakatos AE, et al.: Definitive irradiation in carcinoma of the vagina: long-term evaluation of results. Int J Radiat Oncol Biol Phys 15 (6): 1283-90, 1988.
2. Andersen ES: Primary carcinoma of the vagina: a study of 29 cases. Gynecol Oncol 33 (3): 317-20, 1989.
3. Rubin SC, Young J, Mikuta JJ: Squamous carcinoma of the vagina: treatment, complications, and long-term follow-up. Gynecol Oncol 20 (3): 346-53, 1985.
4. Stock RG, Chen AS, Seski J: A 30-year experience in the management of primary carcinoma of the vagina: analysis of prognostic factors and treatment modalities. Gynecol Oncol 56 (1): 45-52, 1995.
Stage III Vaginal Cancer
Squamous Cell Carcinoma
Standard treatment options:
1. Combination of interstitial, intracavitary, and external-beam radiation therapy (EBRT). EBRT for a period of 5 to 6 weeks (including pelvic nodes) followed by an interstitial and/or intracavitary implant for a total tumor dose of 75 Gy to 80 Gy and a dose to the lateral pelvic wall of 55 Gy to 60 Gy. [1]
2. Rarely, surgery may be combined with the above. [2]
Adenocarcinoma
Standard treatment options:
1. Combination of interstitial, intracavitary, and EBRT as described for squamous cell cancer. [1]
2. Rarely, surgery may be combined with the above. [2]
References:
1. Perez CA, Camel HM, Galakatos AE, et al.: Definitive irradiation in carcinoma of the vagina: long-term evaluation of results. Int J Radiat Oncol Biol Phys 15 (6): 1283-90, 1988.
2. Boronow RC, Hickman BT, Reagan MT, et al.: Combined therapy as an alternative to exenteration for locally advanced vulvovaginal cancer. II. Results, complications, and dosimetric and surgical considerations. Am J Clin Oncol 10 (2): 171-81, 1987.
Stage IVA Vaginal Cancer
Squamous Cell Carcinoma
Standard treatment options:
1. Combination of interstitial, intracavitary, and external-beam radiation therapy (EBRT). [1]
2. Rarely, surgery may be combined with the above. [2]
Adenocarcinoma
Standard treatment options:
1. Combination of interstitial, intracavitary, and EBRT. [1]
2. Rarely, surgery may be combined with the above.
References:
1. Perez CA, Camel HM, Galakatos AE, et al.: Definitive irradiation in carcinoma of the vagina: long-term evaluation of results. Int J Radiat Oncol Biol Phys 15 (6): 1283-90, 1988.
2. Boronow RC, Hickman BT, Reagan MT, et al.: Combined therapy as an alternative to exenteration for locally advanced vulvovaginal cancer. II. Results, complications, and dosimetric and surgical considerations. Am J Clin Oncol 10 (2): 171-81, 1987.
Stage IVB Vaginal Cancer
Squamous Cell Carcinoma
Patients should be considered candidates for one of the ongoing clinical trials to improve therapeutic results. Information about ongoing clinical trials is available from the NCI Web site. Standard treatment is inadequate.
Standard treatment options:
• Radiation (for palliation of symptoms) with or without chemotherapy.
Adenocarcinoma
Patients should be considered candidates for one of the ongoing clinical trials to improve therapeutic results. Information about ongoing clinical trials is available from the NCI Web site.
Standard treatment options:
• Radiation (for palliation of symptoms) with or without chemotherapy.
Recurrent Vaginal Cancer
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 failed in the central pelvis. [1] Most recurrences are in the first 2 years after treatment. In centrally recurrent vaginal cancers, some patients may be candidates for pelvic exenteration or radiation therapy. Clinical trials are also appropriate and should be considered. Information about ongoing clinical trials is available from the NCI Web site. Neither cisplatin nor mitoxantrone has significant activity in recurrent or advanced squamous cell cancer. There is no standard chemotherapy.
References:
1. Stock RG, Chen AS, Seski J: A 30-year experience in the management of primary carcinoma of the vagina: analysis of prognostic factors and treatment modalities. Gynecol Oncol 56 (1): 45-52, 1995.
Changes to This Summary (01/09/2008)
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.
Added Purpose of This PDQ Summary as a section.
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o Treatment options for adult cancers.
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o Tests or procedures that detect specific types of cancer.
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o Risk factors and methods to increase chances of preventing specific types of cancer.
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o Genetics of specific cancers and inherited cancer syndromes, and ethical, legal, and social concerns.
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o Information about complementary and alternative forms of treatment for patients with cancer.
Important:
This information is intended mainly for use by doctors and other health care professionals. If you have questions about this topic, you can ask your doctor, or call the Cancer Information Service at 1-800-4-CANCER (1-800-422-6237).
Date last modified: 2008-01-09

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