Association of cervical precancer with human papillomavirus types other than 16 among HIV co-infected women

Abstract

Background HIV-seropositive women face high risk for infection with oncogenic human papillomavirus (oncHPV) types, abnormal Pap test results, and precancer, but cervical cancer risk is only modestly increased. Human papillomavirus (HPV)16 is highly oncogenic but only weakly associated with HIV status and immunosuppression, suggesting HPV16 may have a greater innate ability to evade host immune surveillance than other oncHPV types, which in turn should result in a greater relative increase in the prevalence of other oncHPV types among women with cervical precancer. Objective We sought to assess whether the underrepresentation of HPV16 among HIV-seropositive relative to HIV-seronegative women remains among those with cervical precancers. Study Design HIV-seropositive and HIV-seronegative women in the Women's Interagency HIV Study were screened for cervical intraepithelial neoplasia (CIN) grade ≥3 (CIN3+). DNA from >40 HPV types was detected by polymerase chain reaction in cervicovaginal lavage specimens obtained at the visit at which CIN3+ was diagnosed. Results HPV16 was detected in 13 (62%) of 21 HIV-seronegative women with CIN3+ but only 44 (29%) of 154 HIV-seropositive women with CIN3+ (P = .01). The lower prevalence of HPV16 in CIN3+ among HIV-seropositive women persisted after controlling for covariates (odds ratio [OR], 0.25; 95% confidence interval [CI], 0.08–0.78). The prevalence of other members of the HPV16-related alpha-9 oncHPV clade as a group was similar in HIV-infected and uninfected women with CIN3+ (OR, 1.02; 95% CI, 0.53–1.94). The prevalence of non-alpha-9 oncHPV types was increased in HIV-seropositive vs HIV-seronegative women with CIN3+ (OR, 3.9; 95% CI, 1.3–11.8). Conclusion The previously demonstrated increase in CIN3+ incidence among HIV-seropositive women is associated with lower HPV16 and higher non-alpha-9 oncHPV prevalence. This is consistent with prior reports that HIV has a weak effect on infection by HPV16 relative to other oncHPV and supports use of nonavalent HPV vaccine in HIV-seropositive women.

Strategies for screening and early detection of anal cancers: A narrative and systematic review and meta‐analysis of cytology, HPV testing, and other biomarkers

“…It has been hypothesized that HPV16 is more capable of evading host‐immune control than other carcinogenic types. In patients who have impaired immune function, other genotypes may persist longer and cause precancers or cancers more often compared with immune‐competent individuals . This could explain the lower relative proportion of HPV16‐positive cancers among HIV‐positive versus HIV‐negative men and women (Fig.…”

Association of HIV status with infection by multiple HPV types

“…HPV-16 had the highest prevalence in the study population (regardless of HIV status) ( Figure 1 immunocompetent ones) [19]. By contrast, studies in countries with heterogeneous populations have indicated that HPV-16 continues to have the highest prevalence (regardless of HIV status) and contributes towards development of cervical lesions in the population living with HIV [2,20,21].…”

“…The clinical characteristics (determined exclusively in HIV-positive women) showed that a viral load >100 000 copies/ml (adjusted OR 7.76; 95% CI 1.64-63. 19) was strongly associated with multiple infection; by contrast, women with CD4 cell counts >500 cells/mm 3 were at lower risk of multiple infection (adjusted OR 0.38; 95% CI 0.13-0.98) ( Table 3).…”

“…HPV‐16 had the highest prevalence in the study population (regardless of HIV status) (Figure ); nevertheless, the results regarding this HPV type's contribution to CC development in HIV‐positive women have been contradictory. The Women's Interagency HIV Study (WIHS) found that this HPV type had lower prevalence and weak association with development of high‐grade cervical abnormalities in HIV‐positive women (compared with immunocompetent ones) . By contrast, studies in countries with heterogeneous populations have indicated that HPV‐16 continues to have the highest prevalence (regardless of HIV status) and contributes towards development of cervical lesions in the population living with HIV .…”

Epidemiological evidence that common HPV types may be common because of their ability to evade immune surveillance: Results from the Women's Interagency HIV study

“…For example, the prevalence of HPV16, which causes approximately 55–60% of all cervical cancers in the general population, was found to be the least affected by HIV status and CD4 count of any oncogenic HPV, based on prevalence ratios (PR) in multiplicative multivariate models . This relative independence from host immune status has been interpreted as evidence that HPV16 may have an innate ability to avoid the effects of immunosurveillance, which could partly explain the high prevalence of HPV16 in the general population and its unique carcinogenicity …”