Chlamydia trachomatis infection and risk of cervical intraepithelial neoplasia

Objectives High-risk human papillomavirus (hrHPV) is the primary cause of cervical cancer. As Chlamydia trachomatis is also linked to cervical cancer, its role as a potential co-factor in the development of cervical intraepithelial neoplasia (CIN) grade 2 or higher was examined. Methods The placebo arms of two large, multinational, clinical trials of an HPV6/11/16/18 vaccine were combined. A total of 8441 healthy women aged 15-26 years underwent cervicovaginal cytology (Papanicolaou (Pap) testing) sampling and C trachomatis testing at day 1 and every 12 months thereafter for up to 4 years. Protocol-specified guidelines were used to triage participants with Pap abnormalities to colposcopy and definitive therapy. The main outcome measured was CIN. Results At baseline, 2629 (31.1%) tested positive for hrHPV DNA and 354 (4.2%) tested positive for C trachomatis. Among those with HPV16/18 infection (n = 965; 11.4%) or without HPV16/18 infection (n = 7382, 87.5%), the hazard ratios (HRs) associated with development of any CIN grade 2 according to baseline C trachomatis status were 1.82 (95% CI: 1.06 to 3.14) and 1.74 (95% CI 1.05 to 2.90), respectively. The results were comparable when only the 12 most common hrHPV infections were considered, but the excess risk disappeared when the outcome was expanded to include CIN grade 3 or worse. Conclusion Further studies based on larger cohorts with longitudinal follow-up in relation to the C trachomatis acquisition and a thorough evaluation of temporal relationships of infections with hrHPV types, C trachomatis and cervical neoplasia are needed to demonstrate whether and how in some situations C trachomatis sets the stage for cervical carcinogenesis. Trial registration NCT00092521 and NCT00092534

Identification of a better Homo sapiens Class II HDAC inhibitor through binding energy calculations and descriptor analysis

Human papillomaviruses (HPVs) are the most common on sexually transmitted viruses in the world. HPVs are responsible for a large spectrum of deseases, both benign and malignant. The certain types of HPV are involved in the development of cervical cancer. In attemps to find additional drugs in the treatment of cervical cancer, inhibitors of the histone deacetylases (HDAC) have received much attention due to their low cytotoxic profiles and the E6/E7 oncogene function of human papilomavirus can be completely by passed by HDAC inhibition. The histone deacetylase inhibitors can induce growth arrest, differentiation and apoptosis of cancer cells. HDAC class I and class II are considered the main targets for cancer. Therefore, the six HDACs class II was modeled and about two inhibitors (SAHA and TSA) were docked using AutoDock4.2, to each of the inhibitor in order to identify the pharmacological properties. Based on the results of docking, SAHA and TSA were able to bind with zinc ion in HDACs models as a drug target. SAHA was satisfied almost all the properties i.e., binding affinity, the Drug-Likeness value and Drug Score with 70% oral bioavailability and the carbonyl group of these compound fits well into the active site of the target where the zinc is present. Hence, SAHA could be developed as potential inhibitors of class II HDACs and valuable cervical cancer drug candidate

Progression and regression of incident cervical HPV 6, 11, 16 and 18 infections in young women

<p>Abstract</p> <p>Background</p> <p>We describe type-specific progression, regression and persistence of incident human papillomavirus (HPV)-6-11-16 and -18 infections, along with type distribution in cervical intra-epithelial neoplasia (CIN) lesions.</p> <p>Methods</p> <p>The study population consisted of 16–23 year-old women undergoing Pap testing and cervical swab polymerase chain reaction testing for HPV DNA at approximate 6 month intervals for up to 4 years in the placebo arm of a clinical trial of an HPV 16-vaccine. HPV types in incident infections were correlated with types in lesion biopsy specimens.</p> <p>Results</p> <p>56.7% of CIN-1 and nearly one-third of CIN-2/3 lesions following incident HPV-6-11-16 or -18 infections did not correlate with the incident infection HPV type. Cumulative 36-month progression rates to CIN-2/3 testing positive for the relevant HPV type were highest for HPV-16 infections (16.5%), followed by HPV-18 (8.2%). Overall, 26.0% of CIN-1, 50.0% of CIN-2 and 70.6% of CIN-3 biopsies tested positive for HPV-6-11-16-18 infections.</p> <p>Conclusion</p> <p>Women with a given HPV type may often be co-infected or subsequently infected with other types which may lead to subsequent cervical lesions. This issue has been addressed in this study reporting data for the natural history of HPV-6-11-16 and -18 infections and is a relevant consideration in designing future studies to evaluate the incidence/risk of CIN following other type-specific HPV infections.</p

Polymer Crystallization in 25 nm Spheres

Crystallization within the discrete spheres of a block copolymer mesophase was studied by time-resolved x-ray scattering. The cubic packing of microdomains, established by self-assembly in the melt, is preserved throughout crystallization by strong interblock segregation even though the amorphous matrix block is well above its glass transition temperature. Homogeneous nucleation within each sphere yields isothermal crystallizations which follow first-order kinetics, contrasting with the sigmoidal kinetics normally exhibited in the quiescent crystallization of bulk polymers.Comment: accepted for publication in Physical Review Letters, 2/28/2000; scheduled for 5/1/2000 issu

A prospective study of the relationship between prediagnostic Human Papillomavirus seropositivity and HPV DNA in subsequent cervical carcinomas

Several prospective studies with invasive carcinoma as endpoint have supported Human Papillomavirus as a cause of cervical carcinoma. However, the largest study used seroepidemiology and did not analyse presence of Human Papillomavirus DNA in the subsequent tumour. Linkage of serum bank registries and cancer registries had identified 196 women with a registered cervical carcinoma after donation of a serum sample. For the present study, biopsies for 127 cases could be located, verified to contain invasive carcinoma and be amplified by PCR. Three control women who had remained alive and without cervical carcinoma during an equal length of follow-up had been matched to each of the case women and tested for HPV antibodies. Presence of Human Papillomavirus DNA in the tumours was analysed by general primer and type specific PCR. HPV16-seropositive women had a relative risk of 4.4 (95% CI: 2.2–8.8) to develop cervical carcinoma carrying HPV16 DNA. By contrast, there was no excess risk for Human Papillomavirus 16-seropositive women to develop cervical carcinoma devoid of HPV16 DNA. Prediagnostic HPV16 seropositivity was strongly correlated with later HPV16 DNA positivity of the tumour (P<0.001) and prediagnostic HPV18 seropositivity correlated with HPV18 DNA in the tumour (P<0.03). The link between prediagnostic seropositivity and type of viral DNA in the cancer implies that the carcinogenic effect of infection with these viruses is dependent on persistent presence of type-specific viral DNA

Program Spending to Increase Adherence: South African Cervical Cancer Screening

Background: Adherence is crucial for public health program effectiveness, though the benefits of increasing adherence must ultimately be weighed against the associated costs. We sought to determine the relationship between investment in community health worker (CHW) home visits and increased attendance at cervical cancer screening appointments in Cape Town, South Africa. Methodology/Principal Findings: We conducted an observational study of 5,258 CHW home visits made in 2003–4 as part of a community-based screening program. We estimated the functional relationship between spending on these visits and increased appointment attendance (adherence). Increased adherence was noted after each subsequent CHW visit. The costs of making the CHW visits was based on resource use including both personnel time and vehicle-related expenses valued in 2004 Rand. The CHW program cost R194,018, with 1,576 additional appointments attended. Adherence increased from 74% to 90%; 55% to 87%; 48% to 77%; and 56% to 80% for 6-, 12-, 24-, and 36-month appointments. Average per-woman costs increased by R14–R47. The majority of this increase occurred with the first 2 CHW visits (90%, 83%, 74%, and 77%; additional cost: R12–R26). Conclusions/Significance: We found that study data can be used for program planning, identifying spending levels that achieve adherence targets given budgetary constraints. The results, derived from a single disease program, are retrospective, and should be prospectively replicated

Routine cervical screening with primary HPV testing and cytology triage protocol in a randomised setting

The role of high-risk human papillomavirus (hrHPV) testing in primary cervical screening has not been established. We generated a randomised evaluation design ultimately to clarify whether primary hrHPV testing implemented into routine screening can bring increase in the programme effectiveness. The aim of the present report on first-year results was to assess the cross-sectional relative validity parameters for routine hrHPV screening, in comparison with conventional screening. An equal number of women invited to routine screening was randomly allocated to primary hrHPV screening (n=7060) and to cytological screening (n=7089). In the hrHPV screening arm, after a single positive hrHPV test result, the need of colposcopy referral was determined by a cytological triage test. Compared with the conventional arm, more colposcopy referrals were made in the hrHPV screening arm (relative risk 1.51, confidence interval 95% 1.03–2.22). Specificity of the primary screening with sole hrHPV test (91.5–92.1%) was much lower than that with the cytology triage (98.7–99.3%), which was not quite as specific as screening with conventional cytology (99.2–99.6%). Compared with conventional cytology, primary screening with hrHPV test results in increased cross-sectional relative sensitivity at the level of all positive lesions at the cost of substantial loss in specificity. With cytology triage, the specificity improves to the level of conventional cytology

The Prevalence of Human Papillomavirus in Pediatric Tonsils: a Systematic Review of the Literature

BACKGROUND: HPV-related head and neck cancer rates have been increasing in recent years, with the tonsils being the most commonly affected site. However, the current rate of HPV infection in the pediatric population remains poorly defined. The objective of this study was to systematically review and evaluate the prevalence and distribution of HPV in the tonsils of pediatric patients undergoing routine tonsillectomy. METHODS AND RESULTS: The literature was searched using PubMed, EMBASE, Scopus, CINAHL, Cochrane Library, and ProQuest Dissertations & Theses Global databases (inception to December 2017) by two independent review authors. Inclusion criteria included articles which evaluated the prevalence of HPV in a pediatric cohort without known warts or recurrent respiratory papillomatosis, those which used tonsil biopsy specimens for analysis, and those with six or more subjects and clear outcomes reported. Eleven studies met the inclusion criteria. Using the Oxford Clinical Evidence-based Medicine (OCEBM) guidelines, two reviewers appraised the level of evidence of each study, extracted data, and resolved discrepancies by consensus. The systematic review identified 11 articles (n = 2520). Seven studies detected HPV in the subject population, with prevalence values ranging from 0 to 21%. The level of evidence for all included studies was OCEBM Level 3. CONCLUSIONS: HPV may be present in pediatric tonsillectomy specimens; however, the largest included study demonstrated a prevalence of 0%. Future testing should be performed using methods with high sensitivities and specificities, such as reverse transcript real-time PCR or digital droplet PCR

Anal HPV Infection in HIV-Positive Men Who Have Sex with Men from China

BACKGROUND: Anal HPV infection, which contributes to the development of anal warts and anal cancer, is well known to be common among men who have sex with men (MSM), especially among those HIV positives. However, HIV and anal HPV co-infection among MSM has not been addressed in China. METHODS: A cross-sectional study was conducted in Beijing and Tianjin, China. Study participants were recruited using multiple methods with the collaboration of local volunteer organizations. Blood and anal swabs were collected for HIV-1 serological test and HPV genotyping. RESULTS: A total of 602 MSM were recruited and laboratory data were available for 578 of them (96.0%). HIV and anal HPV prevalence were 8.5% and 62.1%, respectively. And 48 MSM (8.3%) were found to be co-infected. The HPV genotypes identified most frequently were HPV06 (19.6%), HPV16 (13.0%), HPV52 (8.5%) and HPV11 (7.6%). Different modes of HPV genotypes distribution were observed with respect to HIV status. A strong dose-response relationship was found between HIV seropositivity and multiplicity of HPV genotypes (p<0.001), which is consistent with the observation that anal HPV infection was an independent predictor for HIV infection. CONCLUSIONS: A high prevalence of HIV and anal HPV co-infection was observed in the MSM community in Beijing and Tianjin, China. Anal HPV infection was found to be independently associated with increased HIV seropositivity, which suggests the application of HPV vaccine might be a potential strategy to reduce the acquisition of HIV infection though controlling the prevalence of HPV