Cervical neoplasia in women with and without HIV-related immune depletion : epidemiology and pathogenesis related to HPV types

Abstract

Objectives: Despite current comprehension of HPV epidemiology, the question of how HPV type distribution in the South African population differs from that in the rest of the world remains largely unanswered for both prevalence and oncogenic potential. The primary objective of this study was to investigate the causal relationship between oncogenic or high-risk HPV (HrHPV) types and disease of the cervix, ranging from healthy women to pre-neoplastic and malignant disease. The secondary objective was to investigate the potential differences in the importance of oncogenic HPV types between HIV-infected and HIV-non-infected women. This information is crucial to design country-specific primary and secondary prevention programmes. Methods and materials: This study consists of five smaller studies to address the research problem. Firstly, we investigated the prevalence and distribution of HPV types in sample South African women representative of the general population and subset women with AIDS, both with normal cytology. Secondly, we assessed HPV types present in patients with biopsy-confirmed CIN II/III and to compare HPV type distribution between HIV-infected- and -non-infected women. DNA typing was done on the surface as well as in tissue samples of the dysplastic lesion, in an attempt to identify the lesion-causing virus. Immunohistochemical markers was utilised to insure accurate histological diagnosis and reduce inter- and intra-observer variability. Lastly, we investigated type-specific prevalence in women with invasive cervical cancer (ICC) with and without HIV co-infection. All the above data was then collated to determine the importance of HPV types in cervical oncogenesis in South African women with and without HIV. Results: High-risk HPV DNA was detected from 45% of women with normal cytology, 93% of CIN II/III and 88% of ICC. The four most prevalent HrHPV types found in women without cytological abnormalities were HPV 16, 51, 58 and 45; among women with CIN II/III HPV 16, 52, 35 and 18 were the most common single types; and in ICC samples HPV 16, 18, 45 and 35 were most common. HPV 16, 18, 31, 33, 35, 51, 52 and 56 were all found to be important causes of cervical dysplasia. HPV 16, 18 and 35 were more common in ICC than in women with normal cytology, while HPV 16, 18 and 45 were more common in ICC than preinvasive disease. Infection with HPV and with multiple HPV types was more common among HIVpositive women in all disease groups of the study. Among HIV-positive women HPV 18, 35, 45 and 56 seem to be more important in CIN II/III, while HPV 18, 33, 45 and 58 may be more important causes of ICC. Only HPV 45 was statistically significantly more common among HIV-positive women. Conclusion: The studied population of South African women differs significantly from published data. We also described potential differences in the oncogenic importance of specific HPV types among immune depleted women never discussed before. It is recommended that efforts for both vaccination and screening should be focused only on HPV alpha-9 and alpha-7 groups and firstly only on HPV 16, 18, 45 and 35.