Human papillomavirus type-specific risk of cervical cancer in a population with high human immunodeficiency virus prevalence: case-control study
ABSTRACT There are limited data on human papillomavirus (HPV) type-specific cervical cancer risk among human immunodeficiency virus (HIV)-positive women. Previous studies have suggested that HPV 16 would be relatively less important as a causative agent among HIV-positive compared with HIV-negative women. This study investigates HPV type-specific cervical cancer risk in a population in which HIV is endemic. At the Central Hospital, Maputo, Mozambique, 221 cervical cancer cases and 203 hospital-based controls were consecutively enrolled. HPV typing from cervical samples, HIV testing and recording of socio-demographic factors were performed. Logistic regression modelling was used to assess HPV type-specific risk and effect modification between HIV and HPV infection. Infection with HPV 16, 18 and 'high-risk non-HPV 16/18 types' (HPV 31, 33, 35, 39, 45, 51, 52, 56, 58 and 59) was associated with cervical cancer in both crude and adjusted analyses. HPV 16 and 18 were the most common types detected in cancer biopsies among both HIV-negative and HIV-positive women. There was no significant evidence of effect modification between any HPV type and HIV infection, and there were no significant differences in the HPV type-specific prevalence when cervical cancers among HIV-positive and HIV-negative women were compared. Within the limitations of the study, the relative importance of different HPV types in cervical carcinogenesis appears not to be modified greatly by HIV infection, suggesting that HPV vaccines might not need to be type-specifically modified to be suitable for populations where HIV is endemic.
- SourceAvailable from: Takeshi Kurita
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- "Nonetheless, causal mutations of CCACs have yet to be identified. Unlike squamous cell carcinomas and non-clear cell adenocarcinomas of the cervix (Naucler et al., 2011), CCACs appear to have minimal or no association with the infection of high-risk types of the human papillomavirus (HPV) (Pirog et al., 2000; Goto et al., 2005; Stewart et al., 2006; Liebrich et al., 2009; Waggoner et al., 1994). Loss of function mutations in PTEN (phosphatase and tensin homolog deleted on chromosome 10) have been detected in HPV-negative endometrioid (2/5) and mucinous (2/6) cervical adenocarcinomas (Minaguchi et al., 2004; Hashiguchi et al., 2006) as well as CCACs of the ovary (15/40 and 6/22) (Sato et al., 2000). "
ABSTRACT: Exposure to exogenous hormones during development can result in permanent health problems. In utero exposure to diethylstilbestrol (DES) is probably the most well documented case in human history. DES, an orally active synthetic estrogen, was believed to prevent adverse pregnancy outcome and thus was routinely given to selected pregnant women from the 1940s to the 1960s. It has been estimated that 5 million pregnant women worldwide were prescribed DES during this period. In the early 1970s, vaginal clear cell adenocarcinomas (CCACs) were diagnosed in daughters whose mother took DES during pregnancy (known as DES daughters). Follow-up studies demonstrated that exposure to DES in utero causes a spectrum of congenital anomalies in female reproductive tracts and CCACs. Among those, cervical and vaginal adenoses are most commonly found, which are believed to be the precursors of CCACs. Transformation related protein 63 (TRP63/p63) marks the cell fate decision of Müllerian duct epithelium (MDE) to become squamous epithelium in the cervix and vagina. DES disrupts the TRP63 expression in mice and induces adenosis lesions in the cervix and vagina. This review describes mouse models that can be used to study the development of DES-induced anomalies, focusing on cervical and vaginal adenoses, and discusses their molecular pathogenesis.Differentiation 06/2012; 84(3):252-60. DOI:10.1016/j.diff.2012.05.004 · 2.84 Impact Factor
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ABSTRACT: Human papillomavirus (HPV) is the most common viral infection of the reproductive tract, affecting both men and women. High-risk oncogenic types are responsible for almost 90% of anogenital and oropharyngeal cancers including cervical cancer. Some of the HPV "early" genes, particularly E6 and E7, are known to act as oncogenes that promote tumour growth and malignant transformation. Most notably, HPV-16 E7 interacts with the tumour suppressor protein pRb, promoting its degradation, leading to cell cycle dysregulation in infected cells. We have previously shown that an RNA aptamer (termed A2) selectively binds to HPV16 E7 and is able to induce apoptosis in HPV16-transformed cervical carcinoma cell lines (SiHa) through reduction of E7 levels. In this study, we investigated the effects of the A2 aptamer on E7 localisation in order to define its effects on E7 activity. We demonstrate for the first time that E7 localised to the plasma membrane. In addition, we show that A2 enhanced E7 localisation in the ER and that the A2-mediated reduction of E7 was not associated with proteasomal degradation. These data suggest that A2 perturbs normal E7 trafficking through promoting E7 ER retention.Viruses 7(7):3443-3461. DOI:10.3390/v7072780 · 3.28 Impact Factor
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ABSTRACT: The vast majority of women infected with human immunodeficiency virus (HIV) will be co-infected with human papillomavirus (HPV). The interaction between the two sexually transmitted infections appears to be related to the alteration in cell-mediated immunity in HIV infected persons, increased susceptibility, and possibly reactivation of latent HPV infection. Linkage studies of HIV/AIDs and Cancer registries have indicated a 2- to 22-fold increase in cervical cancer in HIV-positive women compared to HIV-negative women. Data on the prevalence of HPV types in invasive cervical carcinoma (ICC) suggest that the proportion of infection with types HPV16/18 (responsible for over 70% of all cervical cancers) is similar in HIV-negative and HIV-positive women. The biological interaction between HIV and HPV needs further elucidation, although there is some evidence that the presence of HPV infection may be associated with increased HIV transmission. Adolescents perinatally infected by HIV are known to have higher rates of HPV infection and also have been shown to seroconvert in response to HPV vaccination with the quadrivalent vaccine, albeit to lower titers than HIV-negative individuals. Anal cancer incidence is greatly increased in HIV-positive individuals, particularly in HIV-positive men who have sex with men. Screening for anal cancer precursors is feasible and effective; however, the impact on reduction of anal cancer remains to be demonstrated. There are ongoing studies on the safety, immunogenicity, and efficacy of current HPV vaccines in HIV-positive individuals and mature data are awaited. Male circumcision may be another approach to prevention of HPV transmission, which also requires further study. This article forms part of a special supplement entitled "Comprehensive Control of HPV Infections and Related Diseases" Vaccine Volume 30, Supplement 5, 2012.Vaccine 11/2012; 30 Suppl 5(supplement 5):F168-74. DOI:10.1016/j.vaccine.2012.06.045 · 3.49 Impact Factor