With the recent apparent increase in invasive adenocarcinoma of the endocervix, more attention is directed toward AIS. There is evidence that AIS may progress to invasive cancer (108). In a series of 52 cases of adenocarcinoma of the uterine cervix, the results of 18 endocervical biopsies were interpreted as negative 3 to 7 years before the presentation with cancer (130). In five of these cases, AIS was found. In a study of the anatomic distribution of AIS in 23 women, all patients had AIS involving both the surface and the glandular endocervical epithelium, often with the deepest glandular cleft involved (131). The entire endocervical canal was at risk; nearly one-half of the patients had lesions 1.5 to 3 cm from the external os. Overall, 15 patients had unifocal disease, 3 had multifocal disease, and 5 had AIS of undermined type; 11 of the 23 patients had squamous intraepithelial lesions and AIS. In a study of 40 patients with AIS who had cervical conization, 23 of 40 patients (58%) had coexisting squamous intraepithelial lesions and 2 had invasive squamous cell carcinoma (128). Of the 22 patients who underwent hysterectomy, the margins on the cone specimen were positive in 10 patients, and 70% had residual AIS, including 2 patients with foci of invasive adenocarcinoma. One of the 12 patients with negative margins had focal residual adenocarcinoma in the hysterectomy specimen, and 18 women had conization only with negative margins and no relapse of disease after a medium interval of 3 years. Thus, positive margins on the conization specimen are significant findings in these patients (132).
In a more alarming study of 28 patients with AIS, of the 8 patients with positive margins who underwent repeat conization or hysterectomy, 3 had residual AIS and 1 patient had invasive adenocarcinoma (133). Of 10 patients with negative margins who underwent hysterectomy or repeat conization, 4 had residual AIS. One patient in whom the cone margin could not be evaluated had invasive adenocarcinoma. Of the 15 patients treated conservatively with repeat conization of the cervix and close follow-up, 7 (47%) had a recurrent glandular lesion detected after the conization, including invasive adenocarcinoma in 2 women. A glandular lesion was not suspected in 48% of the patients, based on Pap test and endocervical curettage results obtained before conization of the cervix.
AIS must be considered a serious cancer precursor of adenocarcinoma. The entire endocervical canal is at risk, and detection of the lesion with cytologic assessment or endocervical curettage may not be reliable. Any patient with a positive cone margin should undergo repeat conization. If fertility is not desired, a hysterectomy should be performed because of the risk of recurrence, even in the presence of negative margins.
VAIN often accompanies CIN and is believed to share a common etiology (134). Such lesions may be extensions onto the vagina from the CIN, or they may be satellite lesions occurring mainly in the upper vagina. Because the vagina does not have a transformation zone with immature epithelial cells to be infected by HPV, the mechanism of entry for HPV is by way of microabrasions resulting primarily from insertional sexual activity. As these abrasions heal with metaplastic squamous cells, the HPV may begin its growth in a manner similar to that in the cervical transformation zone. VAIN lesions are asymptomatic. Because they often accompany active HPV infection, the patient may report vulvar warts or an odoriferous vaginal discharge from vaginal warts.