KEY POINTS
- Most women diagnosed with vaginal intraepithelial neoplasia (VAIN) have a history of cervical intraepithelial neoplasia.
- Compelling clinical and laboratory data indicate a causal relationship between human papillomavirus and VAIN.
- Like its cervical counterpart, VAIN 3 is thought to have substantial potential to progress to invasive cancer.
- Diagnosis includes careful gross and colposcopic inspection of the entire vagina (with mapping of involved areas), representative colposcopically directed biopsies, and careful palpation of the vaginal walls, especially the vaginal cuff scar.
- Important factors to consider when selecting appropriate treatment for women with VAIN include prior hysterectomy, prior radiation therapy, age, whether she is sexually active, comorbidities, vaginal anatomy, and prior treatments.
We can easily identify vulvar intraepithelial neoplasia (VIN): The patient complains of itching and has a visible lesion. We find cervical intraepithelial neoplasia (CIN) by investigating an abnormal Pap test. But what about vaginal intraepithelial neoplasia (VAIN)? It does not itch and is invisible to the naked eye. A Pap test sometimes catches it, although this test is used mainly to screen for CIN, not VAIN.
VAIN just does not grab our attention. It is uncommon, and invasive vaginal cancer is rare. But before you slip this article into the “obscure disease” file, consider the following:
- VAIN is difficult to diagnose, but some women are at increased risk.
- It is difficult to manage, but understanding the treatment options is important to success.
- The potential for VAIN to evolve into invasive cancer is probably substantial.
- Treatment of invasive vaginal cancer has a high rate of complications and is often unsuccessful.
This article describes the epidemiology, natural history, diagnosis, and treatment of VAIN, focusing primarily on management.
A range of risk factors
As with many uncommon diseases that are difficult to diagnose, good data on the incidence of VAIN are not available. Women diagnosed with VAIN can be in their late teens or senior citizens; mean age is about 50 years.1-5 Race is not mentioned in most studies.
CIN. Although concomitant or subsequent VAIN is very unusual in the approximately 600,000 women identified with CIN each year in the United States, most patients diagnosed with VAIN have a history of CIN. The small number who still have a cervix and are diagnosed with VAIN have a high incidence of concomitant CIN.1 Of women who have had a hysterectomy for CIN, only 1% to 5% are subsequently diagnosed with VAIN.6,7
Since most women who develop vaginal intraepithelial neoplasia have a prior or current history of cervical neoplasia, the “field effect” also renders them at risk for vulvar neoplasia.
HPV. Compelling data indicate a causal relationship between human papillomavirus (HPV) and CIN; the same is true for VAIN.8
Tobacco use. A history of tobacco use is frequent among women diagnosed with VAIN.1
Pelvic radiotherapy is commonly reported in case series.1,3-5 Generally, malignancy is potentially radiation-related if it develops at least 5 to 10 years after treatment.
We do not know whether radiotherapy induces neoplastic transformation in the vagina, but women with a history of radiation warrant long-term follow-up, as they seem to be at increased risk and diagnosis may be difficult.4,5
Chronically immunocompromised women are at particular risk for multifocal lower genital tract neoplasia.9,10
Natural history
The limited data available do suggest that vaginal intraepithelial neoplasia is a premalignant condition.11,12 Unfortunately, little is known about the relationship between severity of the intraepithelial neoplastic process and degree of risk. Natural history studies of VAIN 3 are even more limited than those of CIN 3.
Like its cervical counterpart, VAIN 3 is thought to have substantial potential for progression to invasive cancer.1-4,10-13
EVALUATIONDiagnosis entails inspection, palpation, and directed biopsies
VAIN is most commonly diagnosed after investigation of an abnormal Pap test taken from the vaginal cuff of a woman who has undergone a prior hysterectomy for cervical neoplasia. Occasionally, the disease is identified during colposcopy as extension of a cervical lesion. In either case, VAIN usually involves the upper third of the vagina.1-5,11 A minority of patients will be found to have diffuse multifocal lesions along the vaginal walls.
Adequate diagnosis mandates:
- careful gross and colposcopic inspection of the entire vagina (with mapping of involved areas),
- representative colposcopically directed biopsies,
- careful palpation of the vaginal walls, especially the vaginal cuff scar, and
- in some cases, excision of the vaginal cuff scar.
VAIN is often readily visualized with a colposcope, and the appearance may be more prominent than that of a comparable cervical lesion (FIGURE 1). The lesions are sometimes hyperkeratotic and grossly visible. However, colposcopy of the vagina is more difficult than that of the cervix due to vaginal folding, a larger surface area, and vaginal cuff irregularities.