Risk of cervical precancer and cancer among HIV-infected women with normal cervical cytology and no evidence of oncogenic HPV infection

Abstract

Context: US cervical cancer screening guidelines for human immunodeficiency virus (HIV)-uninfected women 30 years or older have recently been revised, increasing the suggested interval between Papanicolaou (Pap) tests from 3 years to 5 years among those with normal cervical cytology (Pap test) results who test negative for oncogenic human papillomavirus (HPV). Whether a 3-year or 5-year screening interval could be used in HIV-infected women who are cytologically normal and oncogenic HPV-negative is unknown.

Objective: To determine the risk of cervical precancer or cancer defined cytologically (high-grade squamous intraepithelial lesions or greater [HSIL+]) or histologically (cervical intraepithelial neoplasia 2 or greater [CIN-2+]), as 2 separate end points, in HIV-infected women and HIV-uninfected women who at baseline had a normal Pap test result and were negative for oncogenic HPV.

Design, setting, and participants: Participants included 420 HIV-infected women and 279 HIV-uninfected women with normal cervical cytology at their enrollment in a multi-institutional US cohort of the Women's Interagency HIV Study, between October 1, 2001, and September 30, 2002, with follow-up through April 30, 2011. Semiannual visits at 6 clinical sites included Pap testing and, if indicated, cervical biopsy. Cervicovaginal lavage specimens from enrollment were tested for HPV DNA using polymerase chain reaction. The primary analysis was truncated at 5 years of follow-up.

Main outcome measure: Five-year cumulative incidence of cervical precancer and cancer.

Results: No oncogenic HPV was detected in 369 (88% [95% CI, 84%-91%]) HIV-infected women and 255 (91% [95% CI, 88%-94%]) HIV-uninfected women with normal cervical cytology at enrollment. Among these oncogenic HPV-negative women, 2 cases of HSIL+ were observed; an HIV-uninfected woman and an HIV-infected woman with a CD4 cell count of 500 cells/μL or greater. Histologic data were obtained from 4 of the 6 clinical sites. There were 6 cases of CIN-2+ in 145 HIV-uninfected women (cumulative incidence, 5% [95% CI, 1%-8%]) and 9 cases in 219 HIV-infected women (cumulative incidence, 5% [95% CI, 2%-8%]). This included 1 case of CIN-2+ in 44 oncogenic HPV-negative HIV-infected women with CD4 cell count less than 350 cells/μL (cumulative incidence, 2% [95% CI, 0%-7%]), 1 case in 47 women with CD4 cell count of 350 to 499 cells/μL (cumulative incidence, 2% [95% CI, 0%-7%]), and 7 cases in 128 women with CD4 cell count of 500 cells/μL or greater (cumulative incidence, 6% [95% CI, 2%-10%]). One HIV-infected and 1 HIV-uninfected woman had CIN-3, but none had cancer.

Conclusion: The 5-year cumulative incidence of HSIL+ and CIN-2+ was similar in HIV-infected women and HIV-uninfected women who were cytologically normal and oncogenic HPV-negative at enrollment.

Figure 1

Censoring among cytologically normal, oncogenic HPV-negative women in the life-table analysis, by year of follow-up and HIV status. A. Loss to follow-up and censoring for cervical treatment (including hysterectomy) among women in the analysis of HSIL+. In life-table analysis all censoring is assumed to occur uniformly throughout each interval (see Statistical Methods). Thus, in the analysis of HSIL+, 70% (effective sample size 218 + 1 case) of the 255 HIV-uninfected women and 67% (effective sample size 245 non-cases + 1 case) of the 369 HIV-infected women contributed five years of observation. The corresponding rates of follow-up at 3 years of observation were 86% and 81%, respectively. B. Loss to follow-up and censoring for cervical treatment among women in the analysis of CIN-2+. In the analysis of CIN-2+, 82% (113 non-cases + 6 cases) of 145 HIV-uninfected women and 78% (162 non-cases + 9 cases) of 219 HIV-infected women contributed five years of observation to the analysis of CIN-2+. The corresponding rates of follow-up at 3 years of observation were 92% and 88%, respectively.

Figure 1

Censoring among cytologically normal, oncogenic HPV-negative women in the life-table analysis, by year of follow-up and HIV status. A. Loss to follow-up and censoring for cervical treatment (including hysterectomy) among women in the analysis of HSIL+. In life-table analysis all censoring is assumed to occur uniformly throughout each interval (see Statistical Methods). Thus, in the analysis of HSIL+, 70% (effective sample size 218 + 1 case) of the 255 HIV-uninfected women and 67% (effective sample size 245 non-cases + 1 case) of the 369 HIV-infected women contributed five years of observation. The corresponding rates of follow-up at 3 years of observation were 86% and 81%, respectively. B. Loss to follow-up and censoring for cervical treatment among women in the analysis of CIN-2+. In the analysis of CIN-2+, 82% (113 non-cases + 6 cases) of 145 HIV-uninfected women and 78% (162 non-cases + 9 cases) of 219 HIV-infected women contributed five years of observation to the analysis of CIN-2+. The corresponding rates of follow-up at 3 years of observation were 92% and 88%, respectively.