Invasive carcinoma of the vagina is an uncommon tumour constituting less than 2% of all gynaecological malignancies. The incidence is only 1/30th of that of cervical cancer. The age incidence is higher than cervical cancer (reports of mean age vary from 51-65) but the symptoms bear close resemblance. Squamous carcinoma is the predominant histological type and is associated with cervical cancer, cervical intraepithelial disease or prior radiation treatment for anogenital cancer. If a previous diagnosis of cervical cancer was made, vaginal cancer is a primary vaginal cancer if it developed at least 5 years after the cervical cancer diagnosis. Adenocarcinoma (including those in young females exposed to DES in utero) melanoma, sarcoma and embryonal rhabdomyosarcoma in children are rare. The majority (80%) of malignant vaginal tumours result from metastases or extension from nearby organs. There is increasing evidence that vaginal cancer is associated with infection with high risk HPV types. However the progression from the preinvasive form (VAIN III) to invasive cancer is much less common (<5%) and the time course for such progression is unknown. It is sometimes found in association with multifocal preinvasive disease of the lower genital tract in young women, particularly in smokers.
Most patients presents with a painless vaginal discharge and bleeding.
Squamous vaginal cancers are usually located in the upper one-third of the vagina on the posterior wall. Lesions may be exophytic or endophytic with surface ulceration occurring late in the course of the disease. Vaginal cancers are staged clinically. Spread usually occurs by direct extension to pelvic soft tissues, pelvic bones, bladder and rectum. The upper third of the vagina is thought to drain in a way similar to that of the cervix, i.e. to the pelvic nodes, whereas the lower third simulates that of the vulva, i.e. to the inguinal nodes. The middle third may drain either way. Despite the theoretical existence of such a simple stratification, the true picture would appear to be more complicated. There is little information on the incidence of lymph node metastases in vaginal cancer as most patients are not surgically staged.
Haematogenous dissemination to distant organs including lungs liver and bone is a late phenomenon.
Survival is stage dependent with stage I patients having a 75%, stage IIA 55%, stage IIB 43% and stage III 32% and stage IV 0% survival.
I Tumour is limited to the vaginal wall
II Tumour invades paravaginal tissues but not to pelvic wall
III Tumour extends to pelvic wall
IV Tumour invades mucosa of the bladder or rectum and/or extends beyond the true pelvis (bullous oedema is not sufficient evidence to classify a tumour as stage IV
A – Tumour invades bladder and/or rectal mucosa and/or direct extension beyond the true pelvis
B – Spread to distant organs
Due to the relative rarity of this condition, most centres tend to individualize therapy. The close proximity of the bladder and rectum present special problems in management. The predominant mode of therapy is a combination of interstitial, intracavitary and external high voltage pelvic irradiation with surgery being reserved for early stage disease and the treatment of recurrences.
Surgery has a limited role in the management of patients with vaginal cancer. Small lesions involving the upper vagina may be treated by radical hysterectomy and vaginectomy and pelvic lymphadenectomy. In young patients requiring radiation therapy ovarian transposition and possible surgical staging with node dissection may be appropriate. Consideration may be given to construction of a neovagina in younger patients managed surgically.
Patients with stage IVa disease particularly if a rectovaginal or vesicovaginal fistula is present or with central recurrence after radiation therapy, may if suitable be managed by primary pelvic exenteration.
To date there have been few reports on the role of chemotherapy in the management of vaginal tumours. In squamous tumours, chemotherapy regimens similar to those used for cervical squamous carcinoma seem plausible. In tumours with rare histology, treatment should be individualized. Some of these rare tumours in young patients that are chemosensitive may be managed primarily with chemotherapy allowing preservation of fertility.
Generally due to advanced aged and poor performance status of patients with vaginal carcinoma, radiation therapy comprising an integration of teletherapy and intracavitary/interstitial therapy remains the treatment of choice. If the lower third of vagina is involved then groin nodes should also be treated or dissected. If the uterus is intact and the lesion involves the upper vagina, an intrauterine tandem and ovoids can be used. Complications of irradiation include radiation cystitis, vesicovaginal and rectovaginal fistulae and stenosis of vagina, urethra and rectum. Chemoradiation with cisplatin and/or 5-FU is also a reasonable option.
Vaginal melanoma is very uncommon. It is predominantly a disease of postmenopausal women. Vaginal bleeding is the most frequent symptom. Vaginal discharge and the presence of a lump are less frequently reported. It may arise anywhere in the vagina, with a predilection for the lower third, on the anterior wall. Disease may be nonpigmented and frequently ulcerated. Most are deeply invasive; expressed in terms of Chung’s level of invasion most are at level IV. The survival at 2 years following radical surgery is significantly better than with any other therapy. The survival rates at 5 years are equivalent regardless of therapy and are poor.
Treatment must be individualized due to the advanced age of the patients, often with poor performance status and the natural unpredictability of melanoma and its documented poor prognosis. Radical surgery is the mainstay of treatment and will usually involve anterior, posterior or total exenteration. Small upper vaginal lesions may be treated by radical hysterectomy, subtotal vaginectomy and pelvic lymphadenectomy; small distal vaginal lesions may be amenable to partial vaginectomy total or partial vulvectomy and bilateral inguinal-femoral lymphadenectomy. Radiation therapy especially combination of external and interstitial may offer palliation in selected patients. Chemotherapy e.g. methyl-CCNU or dacarbazine (DTIC) has been disappointing.
Such as fibrosarcoma and leiomyosarcomas are rare. They usually present as bulky lesions in upper vagina. Treatment involves surgical excision. The value of adjuvant treatment is not known. Recurrences were seen in tumors larger than 3 cm in diameter with moderate to marked cytologic atypia and more than 5 mitoses per 10HPF.
Also known as embryonal rhabdomyosarcoma are found in the vagina in infancy and childhood; involving the cervix in reproductive years and corpus uteri in postmenopausal years. Conservative surgery in conjunction with preoperative or postoperative chemotherapy (VAC: Vincristine, Actinomycin D and Cytoxan) is the current standard.
Endodermal Sinus Tumor (Yolk Sac Tumor)
Is a rare germ cell tumor occasionally found in extragonadal sites such as vagina. The average age of patients is 10mths, and vaginal bleeding is the main presenting symptom. Serum AFP is elevated. Therapy consists of initial chemotherapy to reduce tumor volume followed by either partial colpectomy and/or radiotherapy.
DES Exposure In Utero
Exposure to DES in utero probably prevents the formation or upward extension of squamous epithelium from the vagina, resulting in vaginal adenosis or the presence of excessive columnar epithelium on the ectocervix extending into the fornices and vagina. The incidence of adenosis in exposed females varies between 30-95%, while a similar, less florid lesion is seen in 3-5% of non-exposed females.
The glandular epithelium is confined to upper vagina in 90-95% of cases, extends to middle third in 5-10% cases and to lower third in only 1% cases. Cervical/vaginal adenosis usually pursues a benign course, transforming via metaplasia to normal squamous epithelium. However there is a modest increased risk of development of cervical dysplasia because of the large area of exposed immature metaplasia in these patients.
Knowledge of exposure is important as (i) there is a small risk of developing clear cell adenocarcinoma of the vagina and cervix (ii) exposure also increases the presence of structural changes in the vagina and cervix and uterus including hooded cervix, pseudopolyps of the cervix, ridge formation and transverse vaginal septum, uterine constriction rings, uterine filling defects, synechia and uterine bicornis. Occurrence is related to dose and time of exposure. The risk is insignificant if exposure occurs after 22 weeks (iii) reproductive function is impaired, related to the structural defects noted, increased rates of endometriosis and increased pregnancy loss and (iv) increased risk of acquiring auto-immune disease
There have been just over 600 cases of clear cell carcinoma of the vagina or cervix reported. Patient’s age range from 14-33 years and the peak age at diagnosis is 19 years. The estimated risk of clear cell adenocarcinoma in an exposed offspring is 1:1000 or less. Approximately 70% of vaginal adenocarcinomas are stage I at diagnosis. The majority of DES exposed individuals are now older than 50 years.
These cancers are treated similarly to squamous lesions, but combined modality is preferred as they tend to locally recur.