Smoking initiation is followed by the early acquisition of epigenetic change in cervical epithelium: a longitudinal study

background: To prove a causal link between an epigenetic change and an environmental or behavioural risk factor for a given disease, it is first necessary to show that the onset of exposure precedes the first detection of that epigenetic change in subjects who are still free of disease. methods: Towards this end, a cohort of women aged 15–19 years, recruited soon after they first had sexual intercourse, were used to provide sequential observations on the relationship between cigarette smoking and the detection in cervical cytological samples of methylated forms of CDKN2A (p16) using nested methylation-specific polymerase chain reaction. results: Among women who remained cytologically normal and who tested negative for human papillomavirus DNA in cervical smears during follow-up, those who first started to smoke during follow-up had an increased risk of acquiring CDKN2A methylation compared with never-smokers (odds ratio=3.67; 95% confidence interval 1.09–12.33; P=0.04). conclusion: Smoking initiation is associated with the appearance of methylated forms of CDKN2A

Persistence of HPV infection and risk of high-grade cervical intraepithelial neoplasia in a cohort of Colombian women

Little is known about the dynamics of human papillomavirus (HPV) infection and subsequent development of high-grade cervical intraepithelial neoplasia (CIN2/3), particularly in women >30 years of age. This information is needed to assess the impact of HPV vaccines and consider new screening strategies. A cohort of 1728 women 15–85 years old with normal cytology at baseline was followed every 6 months for an average of 9 years. Women with squamous intraepithelial lesions were referred for biopsy and treatment. The Kaplan–Meier method was used to estimate the median duration of infection and Cox regression analysis was undertaken to assess determinants of clearance and risk of CIN2/3 associated with HPV persistence. No difference in the likelihood of clearance was observed by HPV type or woman's age, with the exception of lower clearance for HPV16 infection in women under 30 years of age. Viral load was inversely associated with clearance. In conclusion, viral load is the main determinant of persistence, and persistence of HPV16 infections carry a higher risk of CIN2/3

Prevalence of human papillomavirus antibodies in young female subjects in England

Sera from 1483 female subjects in England aged 10–29 years were tested. The age-standardised seroprevalence was 10.7% (95% confidence intervals 9.0–12.3) for human papillomavirus (HPV) 6, 2.7% (1.8–3.6) for HPV 11, 11.9% (10.2–13.6) for HPV 16, 4.7% (3.5–5.8) for HPV 18, and 20.7% (18.6–22.7) for any of the four types

The contribution of HPV18 to cervical cancer is underestimated using high-grade CIN as a measure of screening efficiency

In one geographical area, 14 high-risk human papillomavirus types in cervical intraepithelial neoplasia (CIN2/3; n=139) and cervical squamous cell carcinoma (SCC; n=84) were analysed. HPV18 was more prevalent in SCC than CIN2/3 (OR 9.8; 95% confidence interval: 2.5–39). Other high-risk types prevalences corresponded in CIN2/3 and SCC. Evaluations using CIN2/3 as a measure of efficiency underestimate the contribution of HPV18 to SCC

Multilevel latent class casemix modelling: a novel approach to accommodate patient casemix

<p>Abstract</p> <p>Background</p> <p>Using routinely collected patient data we explore the utility of multilevel latent class (MLLC) models to adjust for patient casemix and rank Trust performance. We contrast this with ranks derived from Trust standardised mortality ratios (SMRs).</p> <p>Methods</p> <p>Patients with colorectal cancer diagnosed between 1998 and 2004 and resident in Northern and Yorkshire regions were identified from the cancer registry database (n = 24,640). Patient age, sex, stage-at-diagnosis (Dukes), and Trust of diagnosis/treatment were extracted. Socioeconomic background was derived using the Townsend Index. Outcome was survival at 3 years after diagnosis. MLLC-modelled and SMR-generated Trust ranks were compared.</p> <p>Results</p> <p>Patients were assigned to two classes of similar size: one with reasonable prognosis (63.0% died within 3 years), and one with better prognosis (39.3% died within 3 years). In patient class one, all patients diagnosed at stage B or C died within 3 years; in patient class two, all patients diagnosed at stage A, B or C survived. Trusts were assigned two classes with 51.3% and 53.2% of patients respectively dying within 3 years. Differences in the ranked Trust performance between the MLLC model and SMRs were all within estimated 95% CIs.</p> <p>Conclusions</p> <p>A novel approach to casemix adjustment is illustrated, ranking Trust performance whilst facilitating the evaluation of factors associated with the patient journey (e.g. treatments) and factors associated with the processes of healthcare delivery (e.g. delays). Further research can demonstrate the value of modelling patient pathways and evaluating healthcare processes across provider institutions.</p

Preferential risk of HPV16 for squamous cell carcinoma and of HPV18 for adenocarcinoma of the cervix compared to women with normal cytology in The Netherlands

We present the type-distribution of high-risk human papillomavirus (HPV) types in women with normal cytology (n=1467), adenocarcinoma in situ (ACIS) (n=61), adenocarcinoma (n=70), and squamous cell carcinoma (SCC) (n=83). Cervical adenocarcinoma and ACIS were significantly more frequently associated with HPV18 (ORMH 15.0; 95% CI 8.6–26.1 and 21.8; 95% CI 11.9–39.8, respectively) than normal cytology. Human papillomavirus16 was only associated with adenocarcinoma and ACIS after exclusion of HPV18-positive cases (ORMH 6.6; 95% CI 2.8–16.0 and 9.4; 95% CI 2.8–31.2, respectively). For SCC, HPV16 prevalence was elevated (ORMH 7.0; 95% CI 3.9–12.4) compared to cases with normal cytology, and HPV18 prevalence was only increased after exclusion of HPV16-positive cases (ORMH 4.3; 95% CI 1.6–11.6). These results suggest that HPV18 is mainly a risk factor for the development of adenocarcinoma whereas HPV16 is associated with both SCC and adenocarcinoma