General Considerations
Vaginal intraepithelial neoplasia (VAIN) can occur as an isolated lesion, but multifocal disease is more common. Although little is known regarding the natural history of VAIN, it is thought to be similar to that of cervical intraepithelial neoplasia (CIN). Many patients may have similar intraepithelial neoplastic lesions involving the cervix or vulva.

At least one-half to two-thirds of patients with VAIN have been treated for similar disease in either the cervix or the vulva. In addition, VAIN can reappear several years later, necessitating long-term follow-up in these patients.

Several investigators have recognized a “field response” involving the squamous epithelium of the lower genital tract including the cervix, vagina, and vulva to be affected simultaneously by the same carcinogenic agent. The vagina lacks a transformation zone, whereas in the cervix immature epithelial cells are infected with HPV. Some theorize that the HPV entry mechanisms involve abrasions from coitus or tampon use. HPV may begin its growth in a healing abrasion in a similar fashion as in the transformation zone.

The upper third of the vagina is vulnerable to the development of dysplasia and carcinoma in situ whether or not hysterectomy has been performed previously for intraepithelial neoplasia. Each of these entities has a potential for progression to invasive cancer. For this reason, women who have had a hysterectomy with a history of HPV or intraepithelial neoplasia should continue to have periodic cytologic screening of the vaginal apex. A similar lesion may develop after prior irradiation for a pelvic malignancy; some authors report a 20% incidence of cervical or vaginal dysplasia. These tumors are usually asymptomatic and detected by routine vaginal cytologic studies. New invasive tumors in an irradiated field usually develop 15-30 years after therapeutic irradiation.

Condylomatous lesions of the lower genital tract often demonstrate associated dysplasias. For this reason a biopsy should be made of condylomatous growth of the vagina prior to treatment.

Pathology

As with other intraepithelial neoplasias occurring in the lower genital tract, VAIN is characterized by a loss of epithelial cell maturation. This is associated with nuclear hyperchromatosis and pleomorphism with cellular crowding. The thickness of the epithelial abnormality designates the various lesions as VAIN I, II, or III. VAIN III is synonymous with carcinoma in situ of the vagina.

Diagnosis

Almost all lesions of VAIN are asymptomatic. Lesions often accompany HPV infection, so patients may complain of vulvar warts. An abnormal Papanicolaou (Pap) smear is usually the first sign of disease. The diagnosis is made by colposcopic examination of the vagina with a directed biopsy. Colposcopic examination of the vagina can be difficult to perform, particularly if a hysterectomy has already been done. Techniques similar to those used for colposcopic examination of the cervix are used for examination of the vagina. After application of 3-5% acetic acid to the vagina, a lesion under the colposcope may appear as white epithelium, and may have mosaicism or punctation. Lugol’s iodine may also help to identify the borders of a lesion. Lesions are often located along the vaginal ridges; they may appear to be raised or have spicules. Because the disease process tends to be multifocal, a thorough examination of the vagina from the introitus to the apex must be conducted.

Treatment

The primary treatment modality for VAIN is surgical excision or carbon dioxide laser ablation. VAIN I lesions usually do not require treatment, as lesions typically regress, are multifocal, and often recur. VAIN II and III can be treated by laser ablation or excision. VAIN III lesions are more often associated with an early invasive lesion; therefore, adequate sampling should be performed before any ablative procedure is employed. If the lesion is focal, it is best removed in its entirety with local excision. When carcinoma in situ of the cervix extends to the upper vagina, the upper third of the vagina can be removed at the time of hysterectomy. If multifocal disease is present, a total vaginectomy may be performed with a split-thickness skin graft vaginal reconstruction. Topical 5-FU may also be used in treating multifocal VAIN. Approximately 80% of patients can expect to have evidence of regression of disease after one to two courses of treatment.

Follow-Up

Intraepithelial neoplasia of the vagina tends to be multifocal, with involvement of the cervix and vulva in many cases. These lesions can be difficult to eradicate with only one treatment modality or treatment session. This group of patients must be monitored closely every 3-4 months with colposcopic examinations of not only the vagina but also the entire lower genital tract.

Hoffman JS, Kumar NB, Morley GW.