Human papillomavirus prevalence and type distribution in invasive cervical cancer in sub-Saharan Africa.

In sub-Saharan Africa, invasive cervical cancer (ICC) incidence and mortality are among the highest in the world. This cross-sectional epidemiological study assessed human papillomavirus (HPV) prevalence and type distribution in women with ICC in Ghana, Nigeria, and South Africa. Cervical biopsy specimens were obtained from women aged ≥ 21 years with lesions clinically suggestive of ICC. Histopathological diagnosis of ICC was determined by light microscopy examination of hematoxylin and eosin stained sections of paraffin-embedded cervical specimens; samples with a confirmed histopathological diagnosis underwent HPV DNA testing by polymerase chain reaction. HPV-positive specimens were typed by reverse hybridization line probe assay. Between October 2007 and March 2010, cervical specimens from 659 women were collected (167 in Ghana, 192 in Nigeria and 300 in South Africa); 570 cases were histologically confirmed as ICC. The tumor type was identified in 551/570 women with ICC; squamous cell carcinoma was observed in 476/570 (83.5%) cases. The HPV-positivity rate in ICC cases was 90.4% (515/570). In ICC cases with single HPV infection (447/515 [86.8%]), the most commonly detected HPV types were HPV16 (51.2%), HPV18 (17.2%), HPV35 (8.7%), HPV45 (7.4%), HPV33 (4.0%) and HPV52 (2.2%). The prevalence of single and multiple HPV infections seemed higher among HIV-positive women and HPV type distribution appeared to differ according to tumor type and HIV status. In conclusion, HPV16, 18, 45 and 35 were the most common HPV types in sub-Saharan African women with ICC and HPV infections were more common in HIV-positive women.

Prevalence of human papillomavirus in women with invasive cervical carcinoma by HIV status in Kenya and South Africa.

Data on the prevalence of human papillomavirus (HPV) types in cervical carcinoma in women with HIV are scarce but are essential to elucidate the influence of immunity on the carcinogenicity of different HPV types, and the potential impact of prophylactic HPV vaccines in populations with high HIV prevalence. We conducted a multicentre case-case study in Kenya and South Africa. During 2007-2009, frozen tissue biopsies from women with cervical carcinoma were tested for HPV DNA using GP5+/6+-PCR assay. One hundred and six HIV-positive (mean age 40.8 years) and 129 HIV-negative women (mean age 45.7) with squamous cell carcinoma were included. Among HIV-positive women, the mean CD4 count was 334 cells/µL and 48.1% were on combined antiretroviral therapy. HIV-positive women had many more multiple HPV infections (21.6% of HPV-positive carcinomas) compared with HIV-negative women (3.3%) (p < 0.001) and the proportion of multiple infections was inversely related to CD4 level. An excess of HPV18 of borderline statistical significance was found in HIV-positive compared with HIV-negative cases (Prevalence ratio (PR) = 1.9, 95% confidence interval (CI): 1.0-3.7, adjusted for study centre, age and multiplicity of infection). HPV16 and/or 18 prevalence combined, however, was similar in HIV-positive (66.7%) and HIV-negative cases (69.1%) (PR = 1.0, 95% CI: 0.9-1.2). No significant difference was found for other HPV types. Our data suggest that current prophylactic HPV vaccines against HPV16 and 18 may prevent similar proportions of cervical SCC in HIV-positive as in HIV-negative women provided that vaccine-related protection is sustained after HIV infection.

Profile of mortality among women with gestational trophoblastic disease infected with the human immunodeficiency virus (HIV): argument for a new poor prognostic factor.

Gestational trophoblastic disease (GTD) encompasses a spectrum of conditions ranging from hydatidiform mole to choriocarcinoma. The management of GTD in association with human immunodeficiency virus (HIV) infection is complicated by the interaction between chemotherapy, antiretroviral therapy, and poor performance status due to HIV-related illnesses. This study describes the profile of mortality of women with GTD in the background of HIV infection. A total of 78 patients with GTD were reviewed retrospectively. There were 53 patients with invasive molar pregnancy and 23 patients with choriocarcinoma. The HIV seroprevalence was 31%. There were 15 deaths (19%). There were 8 HIV-infected (33%) and 7 HIV noninfected (13%) who demised. Of the 8 patients with CD4 counts less than 200 cells/microL, 7 patients demised. There were no mortalities among patients with CD4 counts more than 200 cells/microL. Of the 15 deaths, 5 HIV-infected patients and 5 HIV-noninfected patients received chemotherapy. There were 5 patients admitted in very poor general condition precluding the administration of chemotherapy. Among the 10 patients that received chemotherapy and demised, the causes of death included widespread disease, multiorgan failure, and toxicity due to chemotherapy. These findings highlight the poor outcomes of HIV-infected women with CD4 counts less than 200 cells/microL due to poor tolerance to chemotherapy or poor performance status precluding administration of chemotherapy.

Carraguard Vaginal Gel Safety in HIV-Positive Women and Men in South Africa.

OBJECTIVE: To assess the safety of the candidate microbicide Carraguard gel in HIV-positive women and men. DESIGN: A randomized, placebo-controlled, triple-blinded clinical trial of Carraguard gel when applied vaginally once per day for 14 intermenstrual days by sexually abstinent and sexually active HIV-positive women; and when applied directly to the penis once per day for 7 days by sexually abstinent HIV-positive men. METHODS: In each cohort (n = 20 per cohort), participants were randomized to Carraguard, methylcellulose placebo, or no product (1:1:1). In addition to traditional microbicide trial safety endpoints, the effects of microbicide use on vaginal shedding of HIV-1 RNA and markers of genital inflammation, epithelial sloughing, and microhemorrhage were also explored. RESULTS: Gel compliance was high in both gel-use groups in the 3 cohorts. Carraguard use was not associated with abnormal genital findings, other abnormal clinical findings, markers of genital inflammation, epithelial sloughing or microhemorrhage, or self-reported symptoms in women and men, or with abnormal vaginal flora or genital shedding of HIV-1 RNA in women. Adverse events were mostly mild, not attributed to gel use, and similarly distributed between groups. CONCLUSIONS: Once-daily use of Carraguard for 7 to 14 days appeared to be safe in HIV-positive women and men.

Update on pathophysiologic mechanisms of human papillomavirus.

PURPOSE OF REVIEW: The role of the human papillomavirus in the pathogenesis has been the subject of many publications in the recent literature. The physical state of the human papillomavirus and the role of chromosomal aneuploidy has been reported. This review discusses the recent pathological mechanisms described in the genesis of human papillomavirus-related disease. RECENT FINDINGS: The mere presence of the human papillomavirus is not sufficient for the development of neoplasia. Genetic and other co-factors seem to be necessary for the expression of the invasive phenotype. The expression of human papillomavirus 16 E6-E7 oncogenes results in chromosomal aneuploidy, favouring the integration of high-risk human papillomavirus genomes into cellular chromosomes. The integration of human papillomavirus 16 may not always be required for the progression to the invasive phenotype unlike human papillomavirus 18 DNA. Such integration sites are randomly distributed over the whole genome. The genetic susceptibility of codon 98 of the fragile histadine triad has been elucidated. SUMMARY: Various molecular mechanisms of human papillomavirus-associated neoplasia are discussed. The interaction between HIV and human papillomavirus are complex and favour the persistence and progression of cervical disease. Future research should pave the way for therapeutic vaccine development.