Hookworm infection associates with a vaginal Type 1/Type 2 immune signature and increased HPV load

Knowledge about the distribution of human papillomavirus (HPV) genotypes in invasive cervical cancer is crucial to guide the introduction of prophylactic vaccines. We aimed to provide novel and comprehensive data about the worldwide genotype distribution in patients with invasive cervical cancer. Paraffin-embedded samples of histologically confirmed cases of invasive cervical cancer were collected from 38 countries in Europe, North America, central South America, Africa, Asia, and Oceania. Inclusion criteria were a pathological confirmation of a primary invasive cervical cancer of epithelial origin in the tissue sample selected for analysis of HPV DNA, and information about the year of diagnosis. HPV detection was done by use of PCR with SPF-10 broad-spectrum primers followed by DNA enzyme immunoassay and genotyping with a reverse hybridisation line probe assay. Sequence analysis was done to characterise HPV-positive samples with unknown HPV types. Data analyses included algorithms of multiple infections to estimate type-specific relative contributions. 22,661 paraffin-embedded samples were obtained from 14,249 women. 10,575 cases of invasive cervical cancer were included in the study, and 8977 (85%) of these were positive for HPV DNA. The most common HPV types were 16, 18, 31, 33, 35, 45, 52, and 58 with a combined worldwide relative contribution of 8196 of 8977 (91%, 95% CI 90-92). HPV types 16 and 18 were detected in 6357 of 8977 of cases (71%, 70-72) of invasive cervical cancer. HPV types 16, 18, and 45 were detected in 443 of 470 cases (94%, 92-96) of cervical adenocarcinomas. Unknown HPV types that were identified with sequence analysis were 26, 30, 61, 67, 69, 82, and 91 in 103 (1%) of 8977 cases of invasive cervical cancer. Women with invasive cervical cancers related to HPV types 16, 18, or 45 presented at a younger mean age than did those with other HPV types (50·0 years [49·6-50·4], 48·2 years [47·3-49·2], 46·8 years [46·6-48·1], and 55·5 years [54·9-56·1], respectively). To our knowledge, this study is the largest assessment of HPV genotypes to date. HPV types 16, 18, 31, 33, 35, 45, 52, and 58 should be given priority when the cross-protective effects of current vaccines are assessed, and for formulation of recommendations for the use of second-generation polyvalent HPV vaccines. Our results also suggest that type-specific high-risk HPV-DNA-based screening tests and protocols should focus on HPV types 16, 18, and 45. Copyright © 2010 Elsevier Ltd. All rights reserved.

To determine the association between female genital Schistosoma haematobium infection and HIV. A cross-sectional study with a 1-year follow-up. Gynecological and laboratory investigations were performed for S. haematobium and HIV. Sexually transmitted infections, demographic and urogenital history were analysed as confounders. The participants were 527 sexually active, non-pregnant, non-menopausal women between the ages of 20 and 49 years. The setting was a rural Zimbabwean community where S. haematobium related lesions were found in 46% of the women, HIV in 29% and herpes simplex type- 2 (HSV-2) in 65%. In permanent residents (>3 years residency), HIV was found in 41% (29/70) of women with laboratory proven genital schistosomiasis as opposed to 26% HIV positive (96/375) in the schistosomal ova negative group [odds ratio (OR), 2.1; 95% confidence interval (CI), 1.2-3.5; P = 0.008. In multivariate analysis S. haematobium infection of the genital mucosa was significantly associated with HIV seropositivity (adjusted OR, 2.9; 95% CI, 1.11-7.5; P = 0.030). All seven women who became HIV positive during the study period (seroincidence 3.1%) had signs of S. haematobium at baseline. In accordance with other studies HIV was significantly associated with HSV-2 (OR, 3.0; 95% CI, 1.7-5.3; P < 0.001), syphilis and human papillomavirus. The highest HIV prevalence (45%) was found in the 25-29 years age group. Women with genital schistosomiasis had an almost three-fold risk of having HIV in this rural Zimbabwean community. Prospective studies are needed to confirm the association.

The mammalian intestine is colonized by beneficial commensal bacteria and is a site of infection by pathogens, including helminth parasites. Helminths induce potent immunomodulatory effects, but whether these effects are mediated by direct regulation of host immunity or indirectly through eliciting changes in the microbiota is unknown. We tested this in the context of virus-helminth coinfection. Helminth coinfection resulted in impaired antiviral immunity and was associated with changes in the microbiota and STAT6-dependent helminth-induced alternative activation of macrophages. Notably, helminth-induced impairment of antiviral immunity was evident in germ-free mice, but neutralization of Ym1, a chitinase-like molecule that is associated with alternatively activated macrophages, could partially restore antiviral immunity. These data indicate that helminth-induced immunomodulation occurs independently of changes in the microbiota but is dependent on Ym1. Copyright © 2014, American Association for the Advancement of Science.