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  You are here : Health.am > Health Centers > Cancer Health Center > Vaginal Cancer

Vaginal Cancer

Cancer of the Vagina

- Crowther ME, Lowe DG, Shepherd JH.

The vagina is a muscular tube that extends from the opening of the womb (cervix) to the folds of skin (vulva) between a woman's legs.

It allows blood from periods (menstruation) to pass out of the body, and is the passageway through which babies are born.

It is also called the "birth canal." The vagina connects the cervix (the opening of the womb, or uterus) and the vulva (the external genitalia).

Essentials of diagnosis

  • Asymptomatic: abnormal vaginal cytology.
  • Early: painless bleeding from ulcerated tumor.
  • Late: bleeding, pain, weight loss, swelling.

General Considerations

Primary cancers of the vagina are rare, representing approximately 3% of gynecologic cancers. Approximately 85% are squamous cell cancers, and the remainder, in decreasing order of frequency, are adenocarcinomas, sarcomas, and melanomas. A tumor should not be considered a primary vaginal cancer unless the cervix is uninvolved or only minimally involved by a tumor obviously arising in the vagina. By convention, any malignancy involving both cervix and vagina that is histologically compatible with an origin in either organ is classified as cervical cancer.

Secondary carcinoma of the vagina is seen more frequently than primary vaginal cancers. Secondary, or metastatic, tumors may arise from cervical, endometrial, or ovarian cancer, breast cancer, gestational trophoblastic disease, colorectal cancer, or urogenital or vulvar cancer. Extension of cervical cancer to the vagina is probably the most common malignancy involving the vagina. HPV, early hysterectomy, and prior radiation are possible risk factors for vaginal cancer, but no specific etiologic agent has been identified.

Pathology

Squamous cell carcinoma may be ulcerative or exophytic. It usually involves the posterior wall of the upper third of the vagina, but may be multicentric. Direct invasion of the bladder or rectum may occur. The incidence of lymph node metastases is directly related to the size of the tumor. The route of nodal metastases depends on the location of the tumor in the vagina. Tumors in the lower third metastasize like cancer of the vulva, primarily to the inguinal lymph nodes (Fig 49-8). Cancers of the upper vagina, which is the most common site, metastasize in a manner similar to cancer of the cervix. The lymphatic drainage of the vagina consists of a fine capillary meshwork in the mucosa and submucosa with multiple anastomoses. As a consequence, lesions in the middle third of the vagina may metastasize to the inguinal lymph nodes or directly to the deep pelvic lymph nodes.
GYNECOLOGIC NEOPLASMS

Melanomas and sarcomas of the vagina metastasize like squamous cell cancer, although liver and pulmonary metastases are more common. Nevi rarely occur in the vagina; therefore, any pigmented lesion of the vagina should be excised or biopsied. The anterior surface and lower half of the vagina are the most common sites. Grossly, the tumors are usually exophytic and described as polypoid or pedunculated with secondary necrosis.

Sarcomas of the vagina occur in children younger than 5 years of age and in women in the fifth to sixth decades. Embryonal rhabdomyosarcomas or sarcoma botryoides, replace the vaginal mucosa of young girls and consist of polypoid, edematous, "grapelike" masses that may protrude from the vaginal introitus. Leiomyosarcomas, reticulum cell sarcomas, and unclassified sarcomas occur in older women. The upper anterior vaginal wall is the most common site of origin. The appearance of these tumors depends on the size and the extent of disease at the time of diagnosis.

Clear cell adenocarcinomas arise in conjunction with vaginal adenosis, which, in recent years, has been detected most frequently in young women with a history of exposure to diethylstilbestrol (DES) in utero (Fig 49-9). The Registry of Clear Cell Adenocarcinoma of the Genital Tract in Young Females was established in 1971 to study the clinicopathologic and epidemiologic aspects of these tumors in girls born in 1940 or later, the years during which DES was used during pregnancy. The risk of developing clear cell adenocarcinoma by age 24 years has been calculated to be 0.14-1.4 per 1000 exposed female fetuses. Adenosis vaginae and adenocarcinoma do occur in sexually mature and postmenopausal women.

Metastatic adenocarcinoma to the vagina may arise from the urethra, Bartholin's gland, the rectum or bladder, the endometrial cavity, the endocervix, or an ovary, or it may be metastatic from a distant site. Hypernephroma of the kidney characteristically metastasizes to the anterior wall of the vagina in the lower third. These tumors are not primary vaginal cancers.

Clinical Findings

Vaginal cancer is often asymptomatic, discovered by routine vaginal cytologic examination, and confirmed by biopsy after delineation of the location and extent of the tumor by colposcopy.

Postmenopausal vaginal bleeding and/or bloody discharge are the most common presenting symptoms. Approximately 50% of patients with invasive vaginal cancer report for examination within 6 months after symptoms are noted. Less commonly, advanced tumors may impinge upon the rectum or bladder or extend to the pelvic wall, causing pain or leg edema.

A diagnosis of primary cancer of the vagina cannot be established unless metastasis from another source is eliminated. A complete history and physical examination should be performed, including a thorough pelvic examination, cervical cytologic examination, endometrial biopsy when indicated, complete inspection of the vagina, including colposcopy, and biopsy of the vaginal tumor. Careful bimanual examination with palpation of the entire length of the vagina can detect small submucosal nodules not visualized during the examination.

The staging system for cancer of the vagina is clinical and not surgical (Table 49-2).

Differential Diagnosis

Benign tumors of the vagina are uncommon, are usually cystic, arise from the mesonephric (wolffian) or paramesonephric ducts, and are usually an incidental finding on examination of the anterolateral wall of the vagina (Gartner's duct cyst).

An ulcerative lesion may occur at the site of direct trauma, following an inflammatory reaction caused by prolonged retention of a pessary or other foreign body, or, occasionally, following a chemical burn. Granulomatous venereal diseases seldom affect the vagina but may be diagnosed with appropriate laboratory studies and a biopsy.

Endometriosis that penetrates the cul-de-sac of Douglas into the upper vagina cannot be differentiated from cancer except by biopsy.

Cancer of the urethra, bladder, rectum, or Bartholin's gland may penetrate or extend into the vagina. Cloacogenic carcinoma is a rare tumor of the anorectal region originating from a persistent remnant of the cloacal membrane of the embryo. The tumor accounts for 2-3% of anorectal carcinomas and occurs more than twice as often in women. Although these metastatic tumors often penetrate into the vagina as fungating or ulcerating lesions, they may present as a submucosal mass.

Biopsy should be performed to establish a histologic diagnosis.

Treatment

Following biopsy confirmation of disease, all patients should undergo a thorough physical examination and evaluation of the extent of local and metastatic disease. Pretreatment evaluation may include the following studies: chest radiography, intravenous pyelogram, cystoscopy, proctosigmoidoscopy, and CT scan of the abdomen and pelvis. The treatment of patients with invasive vaginal cancer primarily consists of combined external-beam and internal radiation therapy. In patients in whom coitus is an important factor, surgery should be considered. Also in patients with stages I and IIA lesions, radical hysterectomy with an upper vaginectomy may be performed. Therapy is complicated by the anatomic proximity of the vagina to the rectum, bladder, and urethra. Most primary invasive epidermoid cancers of the vagina are treated by irradiation. Irradiation consists of whole-pelvis external therapy supplemented by internal radiation treatment. Interstitial therapy is commonly used unless there exists a small vault lesion, which may be adequately managed by a tandem and ovoid implant.

A select group of patients with stage III or IV disease may benefit from preoperative whole-pelvic radiation followed by radical surgery. However, most affected patients are treated by irradiation, which consists of whole-pelvis external irradiation followed by intracavitary or interstitial implants, or additional external therapy through a treatment field that has been reduced in size and localized to the affected parametrium. In some cases, carcinoma at the introitus may be treated like cancer of the vulva, using radical vulvectomy and bilateral superficial and deep inguinal lymphadenectomy. A very small and early lesion may be treated by total vaginectomy. However, the close proximity of the bladder and the rectum often precludes conservative surgery. Irradiation is essentially the same as that used for cancers of the upper vagina. When the lower third of the vagina is involved, the inguinal nodes must be treated with either irradiation or inguinal lymphadenectomy.

The principles of treatment of primary adenocarcinoma of the vagina are the same as those for squamous cell cancer. However, preferred therapy for clear cell carcinoma of the vagina and cervix in young women has not been established. Approximately 60% of tumors occur in the upper half of the vagina, and the remainder occur in the cervix. The incidence of nodal metastases is approximately 18% in stage I and 30% or more in stage II disease. If the disease is found sufficiently early and is confined to the upper vagina and cervix, radical abdominal hysterectomy, upper vaginectomy, and pelvic lymphadenectomy with ovarian preservation can be performed. More advanced lesions are treated with irradiation.

Sarcoma botryoides, a variety of rhabdomyosarcoma, is usually seen in patients who are younger than 5 years of age. Radiation therapy or local excision has yielded poor results; thus, historically, pelvic exenteration was the standard of therapy. Primary chemotherapy with vincristine, actinomycin D, and cyclophosphamide plus radiation leads to excellent results in treating patients with this disease. Melanoma of the vagina may be treated with radiation, conservative excision, and/or radical surgery.

Gynecologic Cancers

Epidermoid cancers that recur after primary radiation therapy are usually treated by pelvic exenteration. Chemotherapy for recurrent disease has been relatively ineffective, but multidrug regimens incorporating cisplatin may prove to be more useful.

Prognosis

The size and stage of the disease at the time of diagnosis are the most important prognostic indicators in squamous cell cancers. The 5-year survival rate is approximately 77% in patients with stage I disease, 45% in patients with stage II disease, 31% in patients with stage III disease, and 18% in patients with stage IV disease.

Melanomas—even small ones—are very malignant, and few respond to therapy. The tumor recurs locally and metastasizes to the liver and lungs. Chemotherapy and immunotherapy have been used as adjunctive treatment.

Too few sarcomas of the vagina have been reported to generate survival data. These tumors have a propensity for local recurrence and distant metastases, and the prognosis is usually poor.

REFERENCES

General
Berek JS: Novak's Gynecology. Philadelphia: Williams & Wilkins, 2002.

Preinvasive Disease of the Vulva & Vagina
Davis G, Wentworth J, Richard J: Self-administered topical imiquimod treatment of vulvar intraepithelial neoplasia. J Reprod Med 2000;45:619.

Hart WR: Vulvar intraepithelial neoplasia: Historical aspects and current status. Int J Gynecol Pathol 2001;20:116.

Hillemanns P et al: Integration of HPV-16 and HPV-18 DNA in vulvar intraepithelial neoplasia. Gynecol Oncol [2005; Epub ahead of print]. 2006;100:276.

Jones RW, Rowan DM: Spontaneous regression of vulvar intraepithelial neoplasia 2-3. Obstet Gynecol 2000;96:470.

Joura EA et al: Increasing incidence of vulvar intraepithelial neoplasia and squamous cell carcinoma of the vulva in young women. J Reprod Med 2000;45:613.

McNally OM et al: VIN 3: A clinicopathologic review. Int J Gynecol Cancer 2002;12:490.

Muderspach L et al: A phase I trial of a HPV peptide vaccine for women with high grade cervical and vulvar intraepithelial neoplasia who are HPV 16 positive. Clin Cancer Res 2000;6:3406.

Murta EF et al: Vaginal intraepithelial neoplasia: Clinical-therapeutic analysis of 33 cases. Arch Gynecol Obstet 2005;272:261.

Rome RM et al: Management of vaginal intraepithelial neoplasia: A series of 132 cases with long-term follow-up. Int J Gynecol Cancer 2000;10:382.

Cancer of the Vagina
Miner TJ et al: Primary vaginal melanoma: A critical analysis of therapy. Ann Surg Oncol 2004;11:34.

Samant R et al: Radiotherapy for the treatment of primary vaginal cancer. Radiother Oncol 2005;77:133.

Tjalama WA et al: The role of surgery in invasive squamous carcinoma of the vagina. Gynecol Oncol 2001;81:360.


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