Measuring school level attributable risk to support school-based HPV vaccination programs.

BACKGROUND: In Australia in 2017, 89% of 15-year-old females and 86% of 15-year-old males had received at least one dose of the HPV vaccine. However, considerable variation in HPV vaccination initiation (dose one) across schools remains. It is important to understand the school-level characteristics most strongly associated with low initiation and their contribution to the overall between-school variation. METHODS: A population-based ecological analysis was conducted using school-level data for 2016 on all adolescent students eligible for HPV vaccination in three Australian jurisdictions. We conducted logistic regression to determine school-level factors associated with lower HPV vaccination initiation (< 75% dose 1 uptake) and estimated the population attributable risk (PAR) and the proportion of schools with the factor (school-level prevalence). RESULTS: The factors most strongly associated with lower initiation, and their prevalence were; small schools (OR = 9.3, 95%CI = 6.1-14.1; 33% of schools), special education schools (OR = 5.6,95%CI = 3.7-8.5; 8% of schools), higher Indigenous enrolments (OR = 2.7,95% CI:1.9-3.7; 31% of schools), lower attendance rates (OR = 2.6,95%CI = 1.7-3.7; 35% of schools), remote location (OR = 2.6,95%CI = 1.6-4.3; 6% of schools,) and lower socioeconomic area (OR = 1.8,95% CI = 1.3-2.5; 33% of schools). The highest PARs were small schools (PAR = 79%, 95%CI:76-82), higher Indigenous enrolments (PAR = 38%, 95%CI: 31-44) and lower attendance rate (PAR = 37%, 95%CI: 29-46). CONCLUSION: This analysis suggests that initiatives to support schools that are smaller, with a higher proportion of Indigenous adolescents and lower attendance rates may contribute most to reducing the variation of HPV vaccination uptake observed at a school-level in these jurisdictions. Estimating population-level coverage at the school-level is useful to guide policy and prioritise resourcing to support school-based vaccination programs.

Recurrent disease after treatment for cervical pre-cancer: determining whether prophylactic HPV vaccination could play a role in prevention of secondary lesions.

Existing modalities can effectively treat high-grade cervical intraepithelial neoplasia (CIN) but around 7% of treated women will develop recurrence of CIN grade 2 or above within 2 years of treatment. Post-treatment surveillance is therefore required to detect residual or recurrent disease. Since the implementation of human papillomavirus (HPV) vaccination programs in high-income countries, significant reductions in high-grade CIN have been recorded in vaccinated cohorts who were predominantly HPV-naïve at vaccination. There is still debate as to the extent of potential benefit from vaccination for women previously infected with HPV, given that HPV incidence in women falls with age and previously cleared infection provides at least some protection against reinfection. Whilst vaccination-induced antibodies could prevent type-specific new infections, it is unclear whether vaccination could also prevent reactivation of latent, previously acquired infection and subsequent disease. A review of the available evidence suggests a potential reduction in risk of recurrent disease if women diagnosed and treated for CIN are offered prophylactic vaccines. New modeled analyses and, ideally, a prospectively designed randomized controlled trial in women treated and then randomized to vaccination or placebo would provide much-needed additional evidence to support the effectiveness and cost-effectiveness of offering vaccination to women after treatment for CIN.

Head and neck cancer in Australia between 1982 and 2005 show increasing incidence of potentially HPV-associated oropharyngeal cancers.

BACKGROUND: Although tobacco- and alcohol-associated head and neck cancers are declining in the developed world, potentially human papillomavirus (HPV)-associated oropharnygeal cancers are increasing. METHODS: We analysed oropharyngeal and oral cavity cancer rates in Australia in 1982-2005. Cancers from the oropharynx (base of tongue, tonsil and other specific oropharyngeal sites) were classified as potentially HPV associated (n=8844); cancers in other oral cavity and oropharyngeal sites not previously associated with HPV were classified as comparison (n=28,379). RESULTS: In 2000-2005, an average of 219, 159 and 110 cancers of the tonsil, base of tongue and other oropharyngeal sites were diagnosed annually, with incidences of 1.09 (95% CI: 1.03, 1.15), 0.79 (95% CI: 0.74, 0.84) and 0.55 (95% CI: 0.50, 0.59) per 100,000, respectively. An average of 1242 comparison cancers were diagnosed annually (6.17 (95% CI: 6.03, 6.31) per 100,000). In 1982-2005, there were significant annual increases in tonsil (1.39% (95% CI: 0.88, 1.92%)) and base of tongue cancers in males (3.02% (95% CI: 2.27, 3.78%)) and base of tongue cancer in females (3.45% (95% CI: 2.21, 4.70%)). There was a significant decrease in comparison cancers in men (-1.69% (95% CI: -1.96, -1.42%)), but not in females. CONCLUSION: Potentially HPV-associated oropharyngeal cancer in Australia is increasing; the impact of HPV vaccination on these cancers should be monitored.

Differences in school factors associated with adolescent HPV vaccination initiation and completion coverage in three Australian states.

BACKGROUND: Schools are the primary setting for the delivery of adolescent HPV vaccination in Australia. Although this strategy has achieved generally high vaccination coverage, gaps persist for reasons that are mostly unknown. This study sought to identify school-level correlates of low vaccination course initiation and completion in New South Wales, Tasmania, and Western Australia to inform initiatives to increase uptake. METHODS: Initiation was defined as the number of first doses given in a school in 2016 divided by vaccine-eligible student enrolments. Completion was the number of third doses given in a school in 2015-2016 divided by the number of first doses. Low initiation and completion were defined as coverage ≤ 25thpercentile of all reporting schools. We investigated correlations between covariates using Spearman's rank correlation coefficients. Due to multicollinearity, we used univariable logistic regression to investigate associations between school characteristics and low coverage. RESULTS: Median initiation was 84.7% (IQR: 75.0%-90.4%) across 1,286 schools and median completion was 93.8% (IQR: 86.0%-97.3%) across 1,295 schools. There were strong correlations between a number of school characteristics, particularly higher Indigenous student enrolments and lower attendance, increasing remoteness, higher postcode socioeconomic disadvantage, and smaller school size. Characteristics most strongly associated with low initiation in univariate analyses were small school size, location in Tasmania, and schools catering for special educational needs. Low completion was most strongly associated with schools in Tasmania and Western Australia, remote location, small size, high proportion of Indigenous student enrolments, and low attendance rates. CONCLUSION: This study provides indicative evidence that characteristics of schools and school populations are associated with the likelihood of low initiation and completion of the HPV vaccination course. The findings will guide further research and help target initiatives to improve vaccination uptake in schools with profiles associated with lower coverage.

The utility of seroepidemiology for tracking trends in pertussis infection.

Comparing pertussis epidemiology over time and between countries is confounded by differences in diagnostic and notification practices. Standardized serological methods applied to population-based samples enhance comparability. Population prevalence of different levels of pertussis toxin IgG (PT IgG) antibody, measured by standardized methods, were compared by age group and region of Australia between 1997/1998 and 2002. The proportion of 5- to 9-year-olds with presumptive recent pertussis infection (based on IgG levels >or=62.5 ELISA units/ml) significantly decreased in 2002, consistent with notification data for the same period and improved uptake of booster vaccines following the schedule change from whole-cell to acellular vaccine. In contrast, recent presumptive infection significantly increased in adults aged 35-49 years. Population-based serosurveillance using standardized PT IgG antibody assays has the potential to aid interpretation of trends in pertussis incidence in relation to vaccine programmes and between countries.

Evaluation of p16/Ki-67 dual-stain cytology performed on self-collected vaginal and clinician-collected cervical specimens for the detection of cervical pre-cancer.

OBJECTIVES: To compare the performance of dual immunostaining of p16INK4a and Ki-67 proteins performed on self-collected vaginal specimens and clinician-collected cervical specimens, and to evaluate the performance of this technique in predicting high-grade disease. METHODS: Women aged 30-59 years (n = 1005) were recruited at two well-women clinics in Papua New Guinea. Each woman provided both cervical and vaginal specimens that were tested for high-risk human papillomavirus (hrHPV) DNA using the Xpert HPV Test (Cepheid) at point of care. A subset of paired cervical and vaginal specimens (n = 243) were selected to undergo CINTec® PLUS (Roche) p16/Ki-67 dual-stain cytology and liquid-based cytology (LBC). RESULTS: Fifty-five pairs (22%) were excluded from further analysis because the smears were not assessable. Of the 189 remaining paired specimens, 74 pairs (39.1%) were positive for one or more hrHPV genotypes. When comparing results of the dual stain, the overall percent agreement, positive and negative percent agreements and κ value between the cervical and vaginal specimens were 87.8% (CI 82.3-92.1%), 64.6% (CI 49.5-77.8%), 95.7% (CI 91.0-98.0%) and 0.65 (CI 0.51-0.79%) respectively. The sensitivity of the dual stain performed on the cervical specimen to predict high-grade disease, determined by LBC, was superior to that of the dual stain performed on the vaginal specimen: 100% (CI 84.6-100%) versus 68.2% (CI 45.1-86.1%). CONCLUSION: Although further evaluation may be warranted, these findings indicate that dual-stain testing of vaginal specimens cannot be advocated as part of cervical screening programmes in low- and middle-income countries. However, dual-stain cytology performed on cervical specimens may have a role in quality assurance in such settings.

Evaluation of self-collected vaginal specimens for the detection of high-risk human papillomavirus infection and the prediction of high-grade cervical intraepithelial lesions in a high-burden, low-resource setting.

OBJECTIVES: To compare the performance of self-collected vaginal (V) specimens with clinician-collected cervical (C) specimens for detection of high-risk human papillomavirus (hrHPV) and cervical disease using the Cepheid Xpert HPV, Roche Cobas 4800 HPV and Hologic Aptima HPV assays. METHODS: Women aged 30-59 years (n = 1005) were recruited at two clinics in Papua New Guinea, and they provided specimens for testing at point-of-care using the Xpert HPV Test, and for subsequent testing using the Cobas HPV (n = 981) and Aptima HPV (n = 983) assays. Liquid-based cytology was performed on C specimens to predict underlying high-grade squamous intraepithelial lesions (HSIL). V specimen results of each assay were evaluated against a constructed reference standard and for detection of HSIL or worse. RESULTS: There was substantial (κ >0.6) agreement in hrHPV detection between V and C specimens across all three assays. The sensitivity, specificity, and positive and negative predictive values of Xpert HPV using self-collected V specimens for the detection of HPV type 16 according to the constructed reference standard were 92.1%, 93.1%, 63.6% and 98.9%, respectively; compared with 90.4%, 94.3%, 67.8% and 98.7% for Cobas 4800 HPV; and 63.2%, 97.2%, 75.0% and 95.3% for Aptima HPV. Similar results were observed for all hrHPV types (combined) and for HPV types 18/45, on all three assays. The detection of any hrHPV using self-collected specimens had high sensitivity (86%-92%), specificity (87%-94%) and negative predictive value (>98%) on all assays for HSIL positivity. CONCLUSIONS: Xpert HPV, using self-collected vaginal specimens, has sufficient accuracy for use in point-of-care 'test-and-treat' cervical screening strategies in high-burden, low-resource settings.

Quality of web-based information for osteoarthritis: a cross-sectional study.

BACKGROUND: Osteoarthritis (OA) is a chronic condition that affects over 8.75 million people in the UK. Approximately 43% of people in the UK search for health and medical information online. However, health information on the internet is of variable quality. Research into the quality of online OA information is dated and there is a need to evaluate the existing information. OBJECTIVES: To assess the quality of websites which provide educational information for patients with OA. DESIGN: Electronic cross-sectional survey. METHODS: The search term 'osteoarthritis' was entered into the five popular UK-based search engines in order to identify 50 unique websites. These websites were appraised by two assessors using criteria developed from the available literature and recent guidelines of the National Institute of Health and Care Excellence. The appraisal considered the general quality of the website and OA-specific content. RESULTS: Most of the websites evaluated (34/50, 68%) scored more than half of the maximum available quality score (max score 59). The median total score was 41. For general quality of the website, the median score was nine (range three to 16, out of 16), and for OA-specific content, the median score was 31 (range two to 43, out of 43). Websites of higher quality were created more recently, disclosed sources of information, had external seals of approval and directed the reader on to other relevant websites. CONCLUSIONS: The internet is a potentially useful tool for educating and empowering healthcare consumers. The websites evaluated were generally of a 'high' standard; however, there was wide variation in the quality of information.

HPV vaccination of immunocompromised hosts.

It is well-established that immunocompromised people are at increased risk of HPV-related disease compared with those who are immunocompetent. Prophylactic HPV sub-unit vaccines are safe and immunogenic in immunocompromised people and it is strongly recommended that vaccination occur according to national guidelines. When delivered to immunocompromised populations, HPV vaccines should be given as a 3-dose regimen.

The diagnostic value of plasma free testosterone in non-tumorous and tumorous hyperandrogenism.

The clinical significance of total and free testosterone (T) estimates for the diagnostic approach to hirsute patients was assessed. Plasma T was measured by radioimmunoassay and its non-protein-bound fraction was determined by equilibrium dialysis, thus facilitating the calculation of apparent free T (AFT). The cases of 162 subjects were investigated; the subjects included 75 women in whom glandular androgen release had been defined by selective catheterization. A positive linear correlation was observed between both parameters over a wide range of concentrations (T, 153 to 10,700 pg/ml; AFT, 0.8 to 342 pg/ml; P less than 0.001). Significant differences of mean T and AFT levels were found between healthy control subjects (n = 8) and subjects with non-tumorous hyperandrogenism (n = 60; P less than 0.005). Individual values overlapped considerably; elevated T (greater than 640 pg/ml; 48%) or AFT (greater than 7.2 pg/ml; 52%) were present in only half the hirsute women. However, the upper 95% confidence limits of normal for both indices were exceeded in all patients with androgen-secreting ovarian tumors (n = 7). It is concluded that the indirect estimation of AFT in addition to T is time-consuming, costly, without practical value in selecting the proper treatment, and therefore not mandatory in the routine evaluation of androgenized women.

The interconversion of machine settings and size determinations between seven models of Coulter counter as illustrated by values for human spermatozoa.

Calibration of the Coulter counter Models ZB Industrial, B Industrial D and D Industrial using 21 standard particles is reported using the same method as previously described for the Models B Medical, F and A. All the machines showed significant differences in design and sensitivity. The additional data allowed the relationship between the machine constant and the aperture diameter to be calculated and volume factors were calculated for each combination of settings on each machine. The general method of interconverting size data and machine settings between the instruments was demonstrated using human spermatozoa as an example.

Comparison of the particle size distribution curves determined manually and automatically in an accurately calibrated Coulter Counter.

An accurately calibrated Coulter Counter, Model ZB Industrial, was used to compare the size distribution curves of seven different standard particles obtained by calculation and after the attachment of a Channelyser, Model C-1000 coupled to an XY recorder. Comparisons were made at the modes of the curves and it was found that the automatic method consistently reported the particles to be slightly larger.