The distribution of sexually-transmitted Human Papillomaviruses in HIV positive and negative patients in Zambia, Africa

Abstract

Background: Human Papillomaviruses (HPV) are double-stranded DNA viruses, considered to be the primary etiological agents in cervical intraepithelial neoplasias and cancers. Approximately 15-20 of the 40 mucosal HPVs confer a high-risk of progression of lesions to invasive cancer. In this study, we investigated the prevalence of sexually transmitted HPVs in Human Immunodeficiency Virus (HIV) positive and negative patients in Zambia, Africa. The rate of high-risk HPV genotypes worldwide varies within each country. Thus, we sought to investigate the rates of HPV infection in sub-Saharan Africa and the potential role of HIV in affecting the HPV genotype distribution.

Methods: This retrospective cross-sectional study reports findings on the association and effects of HIV on HPV infections in an existing cohort of patients at University Teaching Hospital (UTH) Lusaka, Zambia. The objective of this study was to assess HPV prevalence, genotype distribution and to identify co-factors that influence HPV infection. Polymerase chain reaction (PCR) with two standard consensus primer sets (CpI/II and GP5+/6+) was used to test for the presence of HPV DNA. Primers specific for beta-actin were used to monitor DNA quality. Vaginal lavage samples, collected between 1998-1999 from a total of 70 women, were part of a larger cohort that was also analyzed for HIV and human herpesvirus infection. Seventy of the samples yielded usable DNA. HIV status was determined by two rapid assays, Capillus and Determine. The incidence of HIV and HPV infections and HPV genotype distributions were calculated and statistical significance was determined by Chi-Squared test.

Results: We determined that most common HPV genotypes detected among these Zambian patients were types 16 and 18 (21.6% each), which is approximately three-fold greater than the rates for HPV16, and ten-fold greater than the rates for HPV18 in the United States. The worldwide prevalence of HPV16 is approximately 14% and HPV18 is 5%. The overall ratio of high-risk (HR) to low-risk (LR) HPVs in the patient cohort was 69% and 31% respectively; essentially identical to that for the HR and LR distributions worldwide. However, we discovered that HIV positive patients were two-times as likely to have an HR HPV as HIV negative individuals, while the distribution of LR HPVs was unaffected by HIV status. Interestingly, we observed a nine-fold increase in HPV18 infection frequency in HIV positive versus HIV negative individuals.

Conclusion: The rate of oncogenic HPVs (type 16 and 18) in Zambia was much higher than in the U.S., potentially providing an explanation for the high-rates of cervical cancer in Zambia. Surprisingly, we discovered a strong association between positive HIV status and the prevalence of HR HPVs, and specifically HPV18.

Figure 1

a. HPV infections are graphed by risk type comparing worldwide and Zambian HPV distributions. The worldwide HPV distribution data was adapted from Clifford et al. (2005) and Peyton etal. (2001) [4] [5] [See Additional file 1]. High-risk (HR; blue) and Low-risk (LR; red) HPV distributions among Zambian and worldwide populations. 1b. HPV infections by risk type in relation to HIV status. High-risk (HR; blue) and Low-risk (LR; red) HPV distributions are graphed as a function of HIV status for Zambian study participants. The distribution of HR and LR HPVs is displayed as the percent of HPV infections in participants. Positive HIV status is associated with a higher prevalence of HR HPV infections.

Figure 2

The frequency of HPV genotypes in Zambia as compared to the worldwide HPV distribution. The worldwide HPV data was adapted from Clifford et al. (2005) and Peyton et al. (2001) [4] [5]. Both HPV16 and HPV18 were present at 21.6% compared to 14% and 5%, for HPV16 and HPV18, respectively.

Figure 3

a The incidence of HPV was calculated as a function of HIV status. The data was normalized as percent incidence to assesses possible effects or associations of HIV status with HPV infection. 3b. The prevalence of HPV genotypes present in patients was assessed for both HIV positive (black) and negative patients (gray). The graph displays HPV genotypes on the x-axis and the frequency of each genotype on the y-axis. HR indicates high-risk strains and LR, represents the low-risk strains.