HPV types present in invasive cervical cancers of HIV‐seropositive women

Abstract

A recent report by De Vuyst et al. 1 found that the prevalence of human papillomavirus (HPV) 16, the most important oncogenic HPV type, was similar in cervical cancer specimens obtained from HIV-seropositive and HIV-seronegative women in Kenya (41 and 44%, respectively). These data are important, since they suggest that current HPV vaccines containing HPV 16 and 18 (if effective in HIV-seropositive patients) have the potential to prevent many cancers in this and similar settings.The findings were also something of a surprise. Prior reports had led to predictions that HPV 16 would be under-represented (and other oncogenic HPV types overrepresented) in cervical cancer specimens among HIVseropositive compared with HIV-seronegative women. In particular, a meta-analysis of studies from around the world found that HPV 16 was significantly less prevalent in high grade squamous intraepithelial lesions (HSILs) from HIVseropositive women than in the general female population, 2 and two large, independent cohorts found that the prevalence of HPV 16 was more weakly associated with CD41 T-cell count than the prevalence of any other HPV type. 3 HPV 16's relative independence from immune status in these studies has been interpreted as evidence that HPV 16 may be innately better than other HPV types at avoiding the effects of immune surveillance and, thereby, less affected by changes in immune status.The disconnect between these prior reports and the study in Kenya can have several possible explanations, including: (i) The prior data showing a weak association of HPV 16 with host immune status were incorrect; (ii) The HPV 16-immune status association is (as reported) weak during the early stages of cervical tumorigenesis. However, it is the accumulation of relevant genetic mutations that is most important in the etiopathogenesis of frank carcinoma; (iii) The differences in HPV natural history between HIV-seropositive and HIV-seronegative women is not as strong in Kenya as it is in Europe and North America.The latter explanation may be the most likely (and most intriguing). Micronutrient deficiencies and chronic infections, especially helminthic infections, are common in many developing economic settings, and can create a relative immunosuppressive state. 4 This might make HIV-seronegative women less immunologically distinct from HIV-seropositive women, and could, in theory, contribute to the high cervical cancer rates common in such settings. The authors, in fact, correctly point out that studies in Africa have often found weaker associations between cervical cancer and HIV/AIDS than have been reported in Europe and North America.It is also possible, however, that technical issues have led to underestimation of the effects of HIV/AIDS on risk of cervical cancer in Africa. The only truly population-based study (e.g., involving linkage between a cancer registry and AIDS registry; similar to those conducted in the US 5,6 ) found a significant association between HIV/AIDS and risk of cervical cancer in Uganda. 7 Moreover, De Vuyst ...

HPV Genotype Distribution in Cervical Intraepithelial Neoplasia among HIV-Infected Women in Pune, India

“…This is likely reflective of the loss of immune control against non-HPV16 genotypes in the context of severe immune suppression, and thus a relative preponderance along with HPV16. [14], [26] Yet, in our study we did not observe an increase of non-HPV16 carcinogenic genotypes with worsening immune status; while HPV16 was higher in women with lower CD4 counts and those currently taking cART. In fact, other than HPV16, we did not see any differences by ART status in any carcinogenicity grouping (data not shown).…”

“…It has been hypothesized HPV16 has better evolutionary ability to escape the effects of immune surveillance, while non-HPV16 genotypes are often better controlled by immune response. [26], [27] Some studies, especially in those conducted in severely immunocompromised women and those not accessing ART [14], [27], [28] have reported higher relative preponderance of non-HPV16 genotypes. This is likely reflective of the loss of immune control against non-HPV16 genotypes in the context of severe immune suppression, and thus a relative preponderance along with HPV16.…”

The Burden of Human Papillomavirus Infections and Related Diseases in Sub-Saharan Africa

“…HPV type 16 is the most common genotype, as in HIV-uninfected populations, although the relative proportion of HPV16 compared to other carcinogenic HPV types is influenced by the degree of immunosuppression [28,56,57]. In addition to a wider variety and multiplicity of carcinogenic HPV types, HIV-infected individuals also have a high prevalence of non-carcinogenic HPV types, or HPV types with unknown carcinogenicity [58].…”

Association between cervical dysplasia and human papillomavirus in HIV seropositive women from Johannesburg South Africa

“…Data concerning the relative importance of the most common HPV types in ICC among HIV-seronegative women (type 16) have been inconsistent among HIV-seropositive women [4, 16] and [17]. These data have important implications for currently available HPV prophylactic vaccines targeting oncogenic HPV types 16 and 18 [18, 19].…”