Abstract and Introduction
Abstract
Objective: HIV infection and low CD4 T-cell count are associated with an increased risk of persistent oncogenic human papillomavirus infection—the major risk factor for cervical cancer. Few reported prospective cohort studies have characterized the incidence of invasive cervical cancer (ICC) in HIV-infected women.
Methods: Data were obtained from HIV-infected and -uninfected female participants in the North American AIDS Cohort Collaboration on Research and Design with no history of ICC at enrollment. Participants were followed from study entry or January 1996 through ICC, loss to follow-up, or December 2010. The relationship of HIV infection and CD4 T-cell count with risk of ICC was assessed using age-adjusted Poisson regression models and standardized incidence ratios. All cases were confirmed by cancer registry records and/or pathology reports. Cervical cytology screening history was assessed through medical record abstraction.
Results: A total of 13,690 HIV-infected and 12,021 HIV-uninfected women contributed 66,249 and 70,815 person-years of observation, respectively. Incident ICC was diagnosed in 17 HIV-infected and 4 HIV-uninfected women (incidence rate of 26 and 6 per 100,000 person-years, respectively). HIV-infected women with baseline CD4 T-cells of ≥350, 200–349, and <200 cells per microliter had a 2.3, 3.0, and 7.7 times increase in ICC incidence, respectively, compared with HIV-uninfected women (Ptrend = 0.001). Of the 17 HIV-infected women, medical records for the 5 years before diagnosis showed that 6 had no documented screening, 5 had screening with low-grade or normal results, and 6 had high-grade results.
Conclusions: This study found elevated incidence of ICC in HIV-infected compared with -uninfected women, and these rates increased with immunosuppression.
Introduction
Human papillomavirus (HPV), a common sexually transmitted virus, is a necessary cause of invasive cervical cancer (ICC). Although the vast majority of cervical HPV infections clear or become undetectable, these infections persist in a subset of women. HIV-infected women are significantly more likely than HIV-uninfected women to have incident and persistent HPV cervical infections and to develop incident precancers such as squamous intraepithelial lesions (SIL) including high-grade SIL (HSIL). Among HIV-infected women, the incidence of HPV infection and SIL increases with lower CD4 T-cell count (CD4). These collective findings strongly support a dose–response relationship between host immune status and the risk of early and intermediate stages of HPV-related tumorigenesis.
There are few data, however, regarding the influence of immunodeficiency on the risk of incident ICC. Few prospective studies of HIV-infected women have had sufficient size to evaluate ICC as an outcome. Though ICC was included as an AIDS-defining event in the 1993 case definition, the evidence for inclusion came from studies of cervical dysplasia rates among HIV-infected women. Inferences regarding the risk of ICC in HIV-infected women have been based primarily on evidence from studies linking HIV/AIDS diagnosis with cancer registries. These studies have reported several fold greater incidence of ICC among women with HIV/AIDS compared with the general population. Linkage studies, however, lack detailed prospective data to assess the temporality between host immunity and cancer risk. To our knowledge, only 1 prospective cohort study examined the association between time-updated current CD4 and ICC. In this study, based in the French Hospital Database on HIV cohort, Guiguet et al reported a significant association of CD4 with risk of ICC.
The current study is the first multicohort prospective investigation of the relationship between HIV infection, immunosuppression, and incident ICC in North America. Using data from 18 collaborating cohorts of the North American AIDS Cohort Collaboration on Research and Design (NA-ACCORD), we examined rates of incident ICC based on cases ascertained through a rigorous standardized validation procedure. The association between CD4 and ICC risk was assessed prospectively to characterize the relevant periods of immunosuppression in relation to ICC risk.