High Rate of Infection by Only Oncogenic Human Papillomavirus in Amerindians

Abstract

Human papillomavirus (HPV), an etiological agent of cervical cancer (CC), has infected humans since ancient times. Amerindians are the furthest migrants out of Africa, and they reached the Americas more than 14,000 years ago. Some groups still remain isolated, and some migrate to towns, forming a gradient spanning urbanization. We hypothesized that, by virtue of their history, lifestyle, and isolation from the global society, remote Amerindian women have lower HPV diversity than do urban women (Amerindian or mestizo). Here we determined the diversity of the 25 most relevant cervical HPV types in 82 Amerindians spanning urbanization (low, medium, and high, consistent with the exposure to urban lifestyles of the town of Puerto Ayacucho in the Venezuelan Amazonas State), and in 29 urban mestizos from the town. Cervical, anal, oral, and introitus samples were taken, and HPVs were typed using reverse DNA hybridization. A total of 23 HPV types were detected, including 11 oncogenic or high-risk types, most associated with CC. Cervical HPV prevalence was 75%, with no differences by group, but Amerindians from low and medium urbanization level had significantly lower HPV diversity than mestizos did. In Amerindians, but not in mestizos, infections by only high-risk HPVs were higher than coinfections or by exclusively low-risk HPVs. Cervical abnormalities only were observed in Amerindians (9/82), consistent with their high HPV infection. The lower cervical HPV diversity in more isolated Amerindians is consistent with their lower exposure to the global pool, and transculturation to urban lifestyles could have implications on HPV ecology, infection, and virulence.IMPORTANCE The role of HPV type distribution on the disparity of cervical cancer (CC) incidence between human populations remains unknown. The incidence of CC in the Amazonas State of Venezuela is higher than the national average. In this study, we determined the diversity of known HPV types (the viral agent of CC) in Amerindian and mestizo women living in the Venezuelan Amazonas State. Understanding the ecological diversity of HPV in populations undergoing lifestyle transformations has important implication on public health measures for CC prevention.

Keywords: diversity; human papillomavirus; lifestyle; oncogenic virus; urbanization.

FIG 1

Diagram of geographic locations included in this study. Sampling was performed at eight locations with different urbanization levels: five locations with low urbanization level (green), one location with medium urbanization level (orange), and two locations with high urbanization (blue). Distances to the urban town were 150 to 210 km (by road and river) for the medium and low urban-level communities. Most communities can be reached only by river; however, some low-level urban communities can be accessed by 1 to 2 days of trekking through the forest. The medium urban level community is located 190 km from an urban location (130 km by river and 60 km by road). The two high urban level communities are located 8 km from each other. The map was generated using Quantum GIS Geographic Information System v. 2.18.14 (https://www.qgis.org/en/site/).

FIG 2

Prevalence and diversity of cervical HPV by subject-based urban groups. (a) HPV general prevalence. (b) HPV risk type prevalence. No prevalence differences were found among Amerindian groups (P = 0.540 by χ² test) or between Amerindians from the high urban group and mestizos (P = 1.000 by χ² test). Unlike mestizos, Amerindian women showed higher prevalence of only high-risk HPV types in relation to low-risk HPV or both types (P = 0.007 in the log linear model). The circles represent mean prevalence, and the bars show 95% confidence intervals (95% CIs). Prevalence that is statistically significantly (P < 0.050) different is indicated by a bar and asterisk. (c) Shannon diversity (Hill number q = 1) of cervical HPV by urban groups, based on a rarefied/extrapolated sample size of 28 women. Amerindians for low and medium urban groups were significantly less diverse than mestizos. There was a nonsignificant tendency to increasing HPV diversity with urbanization. The solid line curve fraction (interpolation) corresponds to the actual number of women sampled. The dashed line corresponds to the estimated diversity (extrapolation). Curved shaded areas represent the 95% CIs estimated from the bootstrap (50 replications). Significant differences are reached when 95% CIs do not overlap. Different letters indicate significant differences. (d) Beta diversity analysis by urban groups. Median distance to the centroid using Sorensen dissimilarity index. No difference among or within a group’s dispersion was observed (P > 0.05, PERMANOVA and permutation test for homogeneity of multivariate dispersions). (e) Heat map of prevalence of cervical HPV types. HPV18 and HPV39 of the α7 family showed the highest relative proportions. HPV L1 region sequences were used to generate a maximum likelihood tree rooted with theta HPV type (not shown). HPV families and their relative proportions (as a percentage; among only HPV-positive samples) are shown on the right. HPV68 and HPV73 were excluded from the tree, since the LiPA25 kit does not discriminate between these two types.