Vaginal intraepithelial neoplasia: Risky and underrecognized

Planned combined treatment using laser vaporization followed by 5-FU cream has been reported efficacious in the treatment of diffuse vaginal condylomata.²¹ Selected patients with VAIN also may benefit,²² such as those with plaque-like disease (where a thick layer of keratin can reduce penetration of the 5-FU cream), diffuse/multifocal disease where laser vaporization is likely to be incomplete, or vaginal anatomy that makes it difficult to accomplish complete laser vaporization.

Vaginectomy is definitive management for selected patients with extensive VAIN. The operation is done transperineally, although hysterovaginectomy may require a combined approach.²³ Leaving the distal third of the vagina intact (when disease distribution allows) makes the operation easier and may help avert iatrogenic urinary incontinence. Follow-up examination—and treatment, if necessary—of the remaining short vaginal stump is fairly easy.

Removal of the vagina is technically demanding in some women. A Schuchardt incision is useful in such instances.

The other obvious disadvantage of vaginectomy is loss of coital function, although placement of a skin graft is an option.

Brachytherapy is another option for treating extensive VAIN in highly selected patients.^24,25

A cylindrical apparatus placed in the vagina delivers radiotherapy to the vaginal epithelium; the likelihood of significant morbidity is low. This method is most applicable to poor surgical candidates with extensive VAIN. Disadvantages include fibrosis of the vagina, limited data on efficacy (and particular concern about inadequate dosing to buried or distorted vaginal cuff epithelium), and potential difficulties with follow-up and treatment of recurrence.^3,5

“Chemosurgery,” specifically 5-FU cream followed by surgical removal of the then-partially-detached VAIN, followed by additional 5-FU cream, has been used effectively at 1 center.¹⁰ Other reported-but-less-investigated methods include cryotherapy, electrocautery, loop electrosurgical excision, and cavitational ultrasonic surgical aspiration (CUSA).^3-5

VAIN in a radiated vagina

Most women who develop VAIN in this scenario received radiation therapy many years earlier for carcinoma of the cervix.^5,11

The most common sites are the upper third to upper half of the remaining vagina, where radiation changes are prominent.

Diagnosis often is problematic due to:

• difficulties with interpreting cytologic preparations in such patients;
• radiation changes in the vagina (pale and fibrotic with telangiectasis), which largely obscure colposcopic findings;
• the difficulty and potential hazards of biopsy of a thin, fibrotic upper vagina; and
• obliterative coaptation of the upper third to half of the vagina.

Significantly abnormal cytology in the absence of a colposcopically identified lesion (or palpable abnormality) is of particular concern. In such patients, view the abnormal cytologic interpretation with caution and consider further initial evaluation, including outside review of the cytology slides, treatment of the vagina with estrogen, and repeat cytologic and colposcopic evaluation.

When there is clear cytologic evidence of a severe abnormality, consider the possibility of occult neoplasia within the coapted upper vagina and/or cervix.

Management of VAIN in a radiated vagina.

Take into account the anatomic distortion of the upper vagina, the thin and fibrotic nature of the epithelium, and the potential for fistula formation with excisional procedures or other treatments that produce injury beneath the surface of the epithelium. Among the options:

• 5-FU cream or laser vaporization. VAIN that is completely visualized within the remaining vagina is probably best treated with one of these modalities, provided the physician is experienced in managing such patients.^5,9
• Excision of the upper vagina,⁵ including the coapted portion (and sometimes the residual cervix with or without the uterus) is appropriate for highly selected cases, but only after careful consideration of:
• the likelihood of finding significant neoplasia,
• the anatomic feasibility (it is desirable to perform the procedure transvaginally), and
• the overall risk versus benefit. Such procedures should be performed only by an experienced physician.

The chronically immunocompromised

These patients often have undergone organ transplants or are human immunodeficiency virus (HIV)-positive. Diffuse HPV infection of the lower genital tract is pervasive in these women,^5,10,26 and diffuse/multifocal lower genital tract intraepithelial neoplasia is often present as well.

These women may be at increased risk for progression to invasive cancer.

Eradication may not be possible. Attempts to eliminate intraepithelial disease are usually unsuccessful.

Management. Many of these women are severely debilitated, with other, more significant medical problems and a short life expectancy. Vigilance is required, as other lower genital tract (and anal) sites are frequently involved. Since eradication of diffuse/multifocal intraepithelial disease is not a realistic goal, treatment followed by chronic suppressive therapy (such as a low intermittent dose of 5-FU) is reasonable.^9,10,22

Another approach is close observation, including frequent examinations, with prompt intervention when invasive disease is suspected.

FOLLOW-UP

After treatment for VAIN, follow-up is similar to that for a comparable cervical lesion. Once the vagina has healed, see the patient every 3 to 6 months for 2 years and annually thereafter. In addition to obtaining vaginal cytology, carefully inspect and palpate the vagina (including the vaginal cuff scar).