Invasive Squamous Cell Carcinoma
Primary invasive carcinoma of the vagina accounts for 12% of all gynecologic malignancies. It is a disease of older women, with the peak incidence in the sixth and seventh decades. Only 10% of these carcinomas occur in women younger than 40 years of age. Squamous cell lesions constitute 80-90% of all invasive malignancies.
Stage 0 : Carcinoma in situ; intraepithelial carcinoma
Stage 1 : Carcinoma limited to vaginal mucosa (wall)
Stage 2 : Subvaginal infiltration into parametrium, not extending to the pelvic wall
Stage 3 : Carcinoma has extended to the pelvic wall
Stage 4 : Carcinoma has extended beyond the true pelvis or involves mucosa of bladder or rectum
Stage 4A : Carcinoma has spread to adjacent organs and/or direct extension beyond the true pelvis
Stage 4B : Carcinoma has spread to distant organs
Modified from International Federation of Gynecology and Obstetrics. Annual report on the results of treatment in gynecological cancer. 22nd edition. Stockholm: FIGO, 1994
Diagnosis
Only about 20% of patients with invasive carcinoma are asymptomatic. Most patients present with abnormal vaginal bleeding or discharge, which may be malodorous. Less frequent complaints include dysuria, urgency, constipation, and pain, all usually occurring with more advanced disease. The upper one third of the vagina is involved in 4050% of cases in reported series. Involvement of the distal third of the vagina may be noted in as many as one third of patients. Posterior wall involvement is more common than lateral or anterior locations. Tumors usually appear exo-phytic or ulcerated. Most gynecologists use FIGO clinical staging (see the box). To rule out adjacent organ primary cancers, staging pelvic examination with biopsies under anesthesia may be indicated.
Once the histologic diagnosis is made, cystoscopy and proctoscopy are indicated in patients with large tumors. Chest X-ray and intravenous pyelography or computed tomography with intravenous and oral contrast usually aid in treatment planning, particularly with clinical stage II or more advanced disease. Magnetic resonance imaging may help in differentiating between fibrotic tissue and tumor infiltration. The use of tumor markers, such as squamous cell carcinoma antigen, has been suggested to assist in surveillance, but these markers are expensive, and few data are available to support their sensitivity or specificity.
Some researchers have recommended surgical evaluation of adjacent nodes for treatment planning. Lymphatics from the upper vagina probably drain in a manner similar to that of the cervix, whereas those from the lower vagina are assumed to drain in a manner similar to that of vulvar lesions. The lymphatic drainage of the vagina is complex and consists of an extensive intercommunicating, interconnecting network. Because of the rarity of vaginal tumors, meaningful surgical studies of lymph node metastasis have not been performed. Lymphangiography may be a less costly and morbid technique for assessing lymph node involvement, particularly in obese patients.
Because patients with vaginal intraepithelial neoplasia are usually asymptomatic, an abnormal Pap test frequently leads to the diagnosis. Rarely, patients may present with postcoital spotting. Colposcopically directed biopsies usually establish the diagnosis. In the patient who has had a hysterectomy, care should be taken to evaluate the pockets sometimes present in the lateral vault areas. During inspection, the speculum blade should be withdrawn slowly and rotated in the partially open position to allow visualization of the entire vaginal tube.
Application of 4-5% acetic acid will cause affected areas to appear white and well demarcated, allowing for target biopsies. Lesions are usually located in the upper one third of the vagina, but because vaginal intraepithelial neoplasia tends to be multifocal, potential lesions in the lower vault should be identified. The lesions may be flat, slightly raised, or warty and granular. Keratinization may obscure any vascular pattern, mosaic, or punctuation. In the postmenopausal patient, lesions are sometimes not easily identified. Topical estrogen for several weeks may help mature vaginal mucosa and allow for easier detection on reexamination. Lugol’s solution may be helpful in determining the extent or location of lesions.
A mixture of 1% lidocaine and vasopressin, injected with a small-gauge spinal needle, will provide local anesthesia for the few patients who need it. The biopsy is often facilitated by grasping tissue adjacent to the lesion with a skin hook and pulling the tissue toward the surgeon. Adequate specimens can be obtained with small, alligator-jaw forceps.
Treatment
Proposed treatments for vaginal intraepithelial neoplasia include surgical excision with partial vaginectomy, laser, topical 5-fluorouracil cream, total vaginectomy with split-thickness skin graft, cryotherapy, and radiation therapy. The mainstay of treatment is wide local excision of the affected area or upper vault vaginectomy. The use of dilute vasopressin injection will facilitate surgery. Laser vaporization has been used, but a biopsy of multiple areas should be performed to rule out invasion. Vasopressin injection also facilitates laser vaporization, and the depth of destruction should be limited to 2 mm. Topical administration of 5-fluorouracil cream has yielded cure rates in selected, compliant patients and may be of particular value in immunosuppressed patients with HPV-associated vaginal intraepithelial neoplasia or in patients who have had previous irradiation. The 5% cream is applied in several regimens, such as every night for 7-10 days with a 2-week break or every week at night for 10 weeks. Caveats to ensure patient compliance and minimize morbidity include inserting one quarter to one third of the applicator high in the vagina before retiring, using a tampon, and protecting the vulva from irritation by use of petroleum jelly.
Use of cryotherapy should be discouraged. Two other, less desirable modalities include total vaginectomy with skin grafting and delivering 6,500-8,000 cGy via an intra-cavitary application. Both procedures can lead to stenosis, scarring, and the rare formation of fistulas.
Primary carcinoma of the vagina is rare and comprises only 1-2% of all female genital malignancies. To be classified as primary vaginal cancer, the lesion must arise in the vagina and must not involve the cervix or vulva. More than 80% of primary vaginal cancers are squamous cell carcinomas, and these squamous cell lesions usually occur in postmenopausal women. The nonsquamous cancers tend to occur in younger females. For example, embryonal rhabdomyosarcomas and endodermal sinus tumors usually occur in children younger than 5 years of age, whereas the rare clear-cell adenocarcinoma, epidemiologically related to diethylstilbestrol (DES), is declining in incidence.
Epidemiologic factors associated with the occurrence of preinvasive and invasive squamous cell lesions include chemotherapy, chronic vaginal irritation, excessive douching, a history of condyloma acuminatum, immunosuppressive treatment or states, long-term pessary use, low socioeconomic status, neglected prolapse, previous irradiation for cervical cancer, primary hysterectomy for cervical intraepithelial neoplasia (CIN) or for benign disease, and multiple sex partners. No single predisposing factor or a combination of factors have been identified.
Vaginal Intraepithelial Neoplasia
Vaginal intraepithelial neoplasia accounts for fewer than 1% of lower genital intraepithelial lesions. Women with vaginal intraepithelial neoplasia tend to be one to two decades younger than those with invasive squamous lesions. Vaginal intraepithelial neoplasia is most often associated with prior or coexistent neoplasia of the cervix or vulva. Prior pelvic irradiation, immunosuppression, or a history of HPV are other common predisposing factors.