Human Papillomavirus (HPV) Test and PAP Smear as Predictors of Outcome in Conservatively Treated Adenocarcinoma In Situ (AIS) of the Uterine Cervix

Abstract

An increasing proportion of cervical carcinomas are adenocarcinomas, and many studies have shown that both adenocarcinoma and adenocarcinoma in situ (AIS) are frequently missed by conventional cytologic study. This study examined clinical outcomes in 42 consecutive women who had conservative treatment of AIS by cervical conization and were prospectively followed up for 40 months on average by colposcopy, Pap smear, biopsy, and human papillomavirus (HPV) testing (with hybrid capture II). Six follow-up assessments were planned at 6-month intervals. All but one of the women had been referred for colposcopy because of an abnormal Pap smear. Only 43% of the 42 women had atypical glandular cells in their referral Pap smears. Colposcopy was negative in 17% of cases and unsatisfactory in another 55%. Twenty-four patients, 57% of those studied, had pure AIS, while 18 had AIS combined with a squamous-cell lesion. Four of the latter patients had invasive squamous-cell carcinoma. Persistent or recurrent disease was documented in 17 women, 40% of those enrolled in the study. The incidence was 19% in patients with free margins and 65% when involved margins were seen on initial conization. Four patients were diagnosed during follow-up as having stage IA1 adenocarcinoma. All 42 women were free of disease at the end of follow-up. Results of HPV testing were a significant predictor of the clearance or persistence of disease (odds ratio, 12.6; 95% confidence interval, 1.18-133.89). In contrast, at no time did the Pap smear have significant predictive power. The combination of a Pap smear and HPV testing was 90% sensitive and 50% specific, with positive and negative predictive values of 53% and 89%, respectively, at initial follow-up. At the second follow-up visit, the combination was 100% sensitive and 53% specific, and had positive and negative predictive values of 40% and 100%, respectively. All AIS lesions had disappeared by the time of the fourth follow-up assessment. A combination of cytology and HPV testing is clearly superior to cytology alone when monitoring women who have been conservatively treated for cervical AIS.