Projected impact of Cervarix™ vaccination on oncogenic human papillomavirus infection and cervical cancer in the United Kingdom.

We developed a dynamic compartmental model to assess the impact of HPV Universal Mass Vaccination (UMV) with Cervarix™, which offers protection against HPV16/18 and cross-protection against other cancer-causing types, using up-to-date efficacy data. Analyses were performed in the UK because of the large amount of high quality epidemiological data available. For each HPV type/group of types considered, the model was calibrated to 14 epidemiological datasets (prevalence of HPV infection, cervical intraepithelial neoplasia (CIN): CIN1, CIN2, CIN3 pre-screening and cervical cancer (CC) incidence over 10 y post-screening). Impacts of cross-protection, female catch-up vaccination, and additional male vaccination on oncogenic infections, high-grade CIN (CIN2+) and CC were evaluated. Our results show that female UMV with 80% coverage and cross-protection against high-risk types resulted in 81% CIN2+ and 88% CC reductions vs. 57% and 75%, respectively, without cross-protection. Vaccinating 40% of males and 80% of females was equivalent to 90% female-only coverage regarding CIN2+ (87% and 87%, respectively) and CC (93% and 94%, respectively) reductions. Female-only coverage of 80% substantially reduced male HPV16 and 18 infection due to herd protection (74% and 89%, respectively). Increasing female coverage to 90% reduced HPV16 and HPV18 infections in males relatively similarly to 80% female combined with 40% male coverage. Model outcomes strengthen previous conclusions about the significant added value of Cervarix™ cross-protection for CC prevention, the primary HPV vaccination public health priority. Regarding female CC prevention and male HPV16/18 infection, small increases in female coverage induce similar benefits to those achieved by additionally vaccinating men with 40% coverage.

The incidence of human papillomavirus infection following treatment for cervical neoplasia: a systematic review.

OBJECTIVE: To systematically review the published literature in order to estimate the incidence and describe the variability of human papillomavirus (HPV) infection in women following treatment for cervical neoplasia. METHODS: Several scientific literature databases (e.g. PubMed, ISI Web of Science) were searched through January 31, 2012. Eligible articles provided data on (i) baseline HPV infection status within 6 months prior to or at time of treatment (pre-treatment); and (ii) HPV test results for women's first visit after treatment occurring within 36 months (post-treatment). We abstracted and summarized the post-treatment incidence of newly detected HPV genotypes that were not present at pre-treatment, overall and stratified by study and other population characteristics. RESULTS: A total of 25 studies were included, reporting post-treatment HPV incidence in nearly 2000 women. Mean patient age ranged from 31 to 43 years (median 36). Most studies used cervical exfoliated cell specimens to test for HPV DNA (n=20; 80%), using polymerase chain reaction (n=21; 84%). Cervical neoplasia treatment included loop electrical excision procedure (n=11; 44%); laser conization (n=2; 8%); laser ablation, surgical conization, cryotherapy, alpha-interferon (n=1; 4% each); or multiple treatment regimens (n=8; 32%). Follow-up times post-treatment ranged from 1.5 to 36 months (median 6). More than half of studies (n=17; 68%) estimated the incidence of any HPV type following treatment, while 7 (28%) focused specifically on high-risk (HR) HPV. HPV incidence after treatment varied widely, ranging from 0 to 47% (interquartile range: 0%-15%) in up to 3 years of follow-up after treatment. Lower HPV incidence was observed among studies that included relatively younger women, used laser conization, focused on HR-HPV rather than overall HPV infection, and had a lower proportion of recurrent cervical disease. CONCLUSIONS: These modest summary incidence estimates from the published literature can guide clinicians, epidemiologists and health economists in developing best practices for post-treatment cervical cancer prevention.

Estimate of the global burden of cervical adenocarcinoma and potential impact of prophylactic human papillomavirus vaccination.

BACKGROUND: Data on the current burden of adenocarcinoma (ADC) and histology-specific human papillomavirus (HPV) type distribution are relevant to predict the future impact of prophylactic HPV vaccines. METHODS: We estimate the proportion of ADC in invasive cervical cancer, the global number of cases of cervical ADC in 2015, the effect of cervical screening on ADC, the number of ADC cases attributable to high-risk HPV types -16, -18, -45, -31 and -33, and the potential impact of HPV vaccination using a variety of data sources including: GLOBOCAN 2008, Cancer Incidence in Five Continents (CI5) Volume IX, cervical screening data from the World Health Organization/Institut Català d'Oncologia Information Centre on HPV and cervical cancer, and published literature. RESULTS: ADC represents 9.4% of all ICC although its contribution varies greatly by country and region. The global crude incidence rate of cervical ADC in 2015 is estimated at 1.6 cases per 100,000 women, and the projected worldwide incidence of ADC in 2015 is 56,805 new cases. Current detection rates for HPV DNA in cervical ADC tend to range around 80-85%; the lower HPV detection rates in cervical ADC versus squamous cell carcinoma may be due to technical artefacts or to misdiagnosis of endometrial carcinoma as cervical ADC. Published data indicate that the five most common HPV types found in cervical ADC are HPV-16 (41.6%), -18 (38.7%), -45 (7.0%), -31 (2.2%) and -33 (2.1%), together comprising 92% of all HPV positive cases. Future projections using 2015 data, assuming 100% vaccine coverage and a true HPV causal relation of 100%, suggest that vaccines providing protection against HPV-16/18 may theoretically prevent 79% of new HPV-related ADC cases (44,702 cases annually) and vaccines additionally providing cross-protection against HPV-31/33/45 may prevent 89% of new HPV-related ADC cases (50,769 cases annually). CONCLUSIONS: It is predicted that the currently available HPV vaccines will be highly effective in preventing HPV-related cervical ADC.

Is the hepatitis C virus epidemic over in Egypt? Incidence and risk factors of new hepatitis C virus infections.

OBJECTIVES: To estimate hepatitis C virus (HCV) incidence rates and identify risk factors for current HCV transmission with emphasis on the role of living with infected household family members in rural Egypt. METHODS: A 4-year population-based, cohort study of seronegative villagers was conducted to identify incident HCV seroconversion cases. A risk factor questionnaire and blood samples for anti-HCV EIA-3 and HCV RNA polymerase chain reaction testing were collected at two rounds of follow-up. Incidence rates, relative risks and 95% confidence interval (CI) were calculated based on a Poisson distribution. A matched case-control analysis to explore specific behavioural predictors of infection was conducted and odds ratios were obtained by conditional logistic regression. RESULTS: Twenty-five participants (11 females) seroconverted in 10,578 person years of follow-up (PY), (incidence rate of 2.4/1000 PY; 95% CI: 1.6-3.5). The median age at seroconversion was 26 years [interquartile range (IQR) 19-35] among males and 20 years (IQR 13-24) among females. The only significant risk factor identified for these cases was receiving injections [adjusted odds ratio (OR(adj))=3.3; 95% CI: 1.1-9.8]. Two of the 17 viraemic seroconvertors were infected with the same strain as at least one of their family members. CONCLUSION: This study identified the important role of injections in spreading HCV infection in this rural community. National healthcare awareness and infection control programmes should be strengthened to prevent further transmission. Screening of families of infected HCV subjects should be an essential part of case management for early detection and management.

Agreement between self- and clinician-collected specimen results for detection and typing of high-risk human papillomavirus in specimens from women in Gugulethu, South Africa.

We assessed the agreement in detection of high-risk human papillomavirus (HPV), as well as specific HPV types, between self- and clinician-obtained specimens for 450 women over 18 years of age attending a community health center in Gugulethu, South Africa. Both self-collected swabs and tampons had high agreement with clinician-obtained brushes when the Roche Reverse Line Blot Assay (RLBA) was used (for swabs, 86% concordance, with a kappa statistic [kappa] of 0.71; for tampons, 89% concordance, with kappa of 0.75). Agreement was lower, although still fair, with the Digene Hybrid Capture 2 test (HC2), with kappa higher for swabs than for tampons (for swabs, 81% concordance, with kappa of 0.61; for tampons, 82% concordance, with kappa of 0.55). Low-risk HPV types were nearly two times more common in self-collected specimens than in clinician-collected specimens tested by RLBA. All 15 women diagnosed with high-grade lesions by cytology tested positive for high-risk HPV with clinician-collected specimens tested by RLBA and HC2, while 11 out of 15 tested positive with self-collected specimens by HC2 and 5 out of 6 tested positive by RLBA. Self-collected specimens can provide valid specimens for HPV testing using nucleic acid amplification tests, although a few cytological abnormalities may be missed.

Menopausal transition: predicting time to menopause for women 44 years or older from simple questions on menstrual variability.

OBJECTIVE: To assess whether menstrual variability predicts time to menopause. DESIGN: Analyses drew on 326 menstruating women, aged 44 to 56, who were followed until they reached menopause or the study ended. The women provided data on their menstrual characteristics at intake. We evaluated the utility of six definitions of menstrual variability for predicting time to ascertained menopause (final menstrual period + 12 months): (1) more than 90 days since the most recent menstrual period (n = 20); (2) 60 or more days of amenorrhea during the previous year (n = 71); (3) cycle lengths that varied by 19 or more days (n = 106); (4) cycle lengths too variable to report a usual length (n = 29); (5) cycles less regular than they had been at age 40 (n = 107); and (6) change in the duration or heaviness of menstrual flow compared with age 40 (n = 255). In addition, we evaluated hot flashes or night sweats during the previous week (n = 50) and age 50 or more years (n = 60) as predictors. RESULTS: Definitions 1 to 5 predicted time to menopause; definition 6 did not. Definition 1 had the highest positive predictive value for ascertained menopause within 2 years and within 4 years; definitions 2 and 4 had low to moderate positive predictive values for ascertained menopause within 2 years but good positive predictive values for ascertained menopause within 4 years. For ascertained menopause within 2 years, definition 2 showed the best balance of sensitivity (94%) and specificity (91%). CONCLUSION: Simple questions about menstrual variability elicit information that is informative about proximity to menopause.