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.