Vaginal intraepithelial neoplasia: Risky and underrecognized
Hysterectomy for cervical neoplasia, radiation for cervical carcinoma, and chronic immunocompromise heighten risk—and both diagnosis and treatment can be tricky.
Vaginal atrophy also creates diagnostic difficulties related to colposcopic assessment, and to overreading of vaginal cytology (eg, when a lesion is interpreted as high-grade dysplasia or suspicious). Reassessment after 4 to 6 weeks of estrogen therapy helps resolve these issues.
FIGURE 1 Colposcopic view of VAIN 3
Note the hyperkeratotic, prominent appearance of the VAIN lesions.
TREATMENT
Because women with VAIN are a heterogeneous group, treatment must be individualized. Important factors to consider when selecting appropriate treatment include prior hysterectomy, prior radiation therapy, age, whether the woman is sexually active, comorbidities, vaginal anatomy, and prior treatments.
Prior hysterectomy
Most women diagnosed with VAIN have previously undergone hysterectomy, usually because of cervical neoplasia.2-5,10 In these women, VAIN is generally confined to the vaginal apex (FIGURE 2).
Watch for occult neoplasia. Buried epithelium within the vaginal cuff scar may harbor occult neoplasia. Patients with VAIN at the vaginal apex5,10,11,13 and a vaginal cuff from a hysterectomy for cervical neoplasia are analogous to women with CIN and an unsatisfactory colposcopy.
Excision is usual management. Most of these women are appropriately managed with excision of the involved vaginal apex, including the cuff scar.1,3-5,11,14 Problematic vaginal shortening is uncommon following this procedure. The status of the resection margin is predictive of the likelihood of recurrence.3
With more extensive vaginal epithelial involvement, consider cuff excision in selected cases to eliminate the potential for occult disease. The remainder of the involved vagina can be treated by other means outlined below.
FIGURE 2 VAIN 3 at vaginal apex
VAIN usually is confined to the apex in women hysterectomized for cervical neoplasia.
When CIN extends onto the vaginal fornix
This is an uncommon scenario, although its underrecognition may explain why some VAIN is diagnosed shortly after hysterectomy for CIN.
Management is simpler than for disease involving the posthysterectomy apex because there is no scarring, distortion, or buried epithelium, and traction on the cervix generally provides good exposure.
Laser vaporization is an option. For many such patients, this is one of the few good indications remaining for laser vaporization.5,15,16
If hysterectomy is indicated, remove the affected portion of the upper vagina along with the cervix.5,17
Multifocal or diffuse pattern: Typical of immunocompromise
Multifocal or diffuse manifestation is likewise uncommon, often involving low-grade neoplasia and condylomatous changes.5,18 This is the pattern typically seen in chronically immunocompromised women.5,10
The natural history of VAIN—especially the malignant potential—is less well understood for women with this disease pattern. When managing such patients, keep in mind the potential for occult neoplasia in the vaginal cuff scar. However, broaden the focus of treatment to encompass the entire vagina. The various management options are described below:
- If the patient has cervical intraepithelial neoplasia 2 or 3, treat with laser, cryotherapy, or large loop excision of the transformation zone at least 2 weeks prior to beginning 5-fluorouracil (5-FU).
- Treat vulvar, anal, or urethral lesions with a laser or local excision prior to 5-FU.
- Treat vulvovaginitis prior to 5-FU.
- Have the patient administer 1/2 vaginal applicator of 5% 5-FU (Efudex; 2.5 g) deep in the vagina weekly at bedtime for 10 weeks. Instruct her to place a tampon or cotton balls into the outer vagina, unless the distal vagina is involved. Also have her apply petroleum jelly to all vulvar tissues, around the urethra, and to the anus. In the morning, she should remove the tampon, wash the vulva with soap and water, and dry carefully. This should be followed by another application of petroleum jelly (sparingly) to vulvar tissues. A mini napkin may help prevent staining of garments.
- When 5-FU treatment ends, have the patient administer 1/3 applicator of vaginal estrogen cream nightly for 2 weeks beginning 3 weeks prior to reevaluation.
- Evaluate with colposcopy and cytology 8 weeks after completing 5-FU therapy.
Observation only is particularly suited for women who have low-grade disease or who are severely debilitated and chronically immunocompromised.
5-fluorouracil (5-FU) cream is a very good treatment when VAIN involves the upper half to two thirds of the vagina.2,9 However, the cream does not reach buried epithelium in the vaginal cuff scar and probably does not consistently treat the lower vagina when applied with the standard vaginal applicator. Applying the cream directly to the lower vagina may be more effective when that region is involved (see “6-step vaginal fluorouracil therapy for intraepithelial neoplasia,” above).
Laser vaporization is well accepted and commonly used.2,9,15,19,20 Advantages are versatility in treatment of multifocal disease without sacrificing vaginal epithelium, and low likelihood of complications. Disadvantages include inability to treat buried vaginal cuff epithelium; technical difficulties in applying the laser to a folding and often distorted (cuff) surface within a confined space; and the expensive equipment, technical support, and surgical expertise required.1,4,5,11,15,16,20
