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Global methylation analysis of gene promoters is promising for detection of high-grade squamous intraepithelial lesions or worse (HSIL+) in high-risk human papillomavirus (hrHPV)-positive women. However, diagnostic performance of methylation data at individual CpG-sites is limited. We explored methylation for predicting HSIL+ in self- and clinician-collected samples from Papua New Guinea. Methylation of EPB41L3 (1-6 CpG-sites), hTERT (1-10 CpG-sites) and FAM19A4 (1-5 CpG-sites) was assessed through pyrosequencing from 44 HPV+ samples (4 cancers, 19 HSIL, 4 low-grade squamous intraepithelial lesions (LSIL), 17 normal). New primers were designed for FAM19A4 directed to the first exon region not explored previously. In clinician-collected samples, methylation at CpG-sites 4 and 5 of EPB41L3 were the best HSIL predictors (AUC >0.83) and CpG-site 4 for cancer (0.925). Combination of EPB41L3 sites 2/4 plus FAM19A4 site 1 were the best HSIL+ markers [100% sensitivity, 63.2% specificity]. Methylation at CpG-site 5 of FAM19A4 was the best HSIL predictor (0.67) in self-collected samples, and CpG-sites 1 and 3 of FAM19A4 for cancer (0.77). Combined, FAM19A4 site 1 plus HPV 16/18 detection yielded sensitivity of 82.6% and specificity of 61.9%. In conclusion, methylation at individual CpG-sites of EPB41L3 and FAM19A4 outperformed global analysis and improved HSIL+ detection, warranting further investigation., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests. AJV, JG, JB, GMM, PJT, SGB, JMK have received subsidized test kits for research from Cepheid. MS, JMLB, GT, DH have received donated test kits for research from Roche, Abbott, Seegene, Cepheid, Aus Diagnostics and Becton Dickinson. AJV and MS jointly lead the Elimination of Cervical Cancer in theWesternPacific (ECCWP) program with philanthropic funding support from the Minderoo Foundation and the Frazer Family Foundation; and equipment, tests and consumables donated by Cepheid for HPV-based cervical screening in Papua New Guinea and Vanuatu. SMG is a member of the Global Advisory Board HPV Merck, and has led investigator-initiated grants from Merck on HPV in young women. All other authors report no potential conflicts., (Copyright © 2024. Published by Elsevier B.V.)

Context.—: Detection of human papillomavirus (HPV) in formalin-fixed, paraffin-embedded (FFPE) tissues may identify the cause of lesions and has value for the development of new diagnostic assays and epidemiologic studies. Seegene Anyplex II assays are widely used for HPV screening, but their performance using FFPE samples has not been fully explored., Objective.—: To validate Anyplex II HPV HR Detection (Anyplex II, Seegene) using FFPE samples., Design.—: We used 248 stored DNA extracts from cervical cancer FFPE samples collected during 2005-2015 that tested HPV positive using the RHA kit HPV SPF10-LiPA25, v1 (SPF10, Labo Biomedical Products) HPV genotyping assay, manufacturer-validated for FFPE samples., Results.—: Of the selected 248 samples, 243 were used in our analysis. Consistent with SPF10 genotyping results, Anyplex II detected all 12 oncogenic types and had an overall HPV detection rate of 86.4% (210 of 243 samples). Anyplex II and SPF10 showed very high agreement for the detection of the 2 most important oncogenic genotypes: HPV 16 (219 of 226; 96.9%; 95% CI, 93.7-98.75) and HPV 18 (221 of 226; 97.8%; 95% CI, 94.9-99.3)., Conclusions.—: Overall results showed that both platforms produced comparable HPV genotyping results, indicating the suitability of Anyplex II for FFPE samples. The Anyplex II assay has the added convenience of being an efficient, single-well semiquantitative polymerase chain reaction assay. Further optimization of Anyplex II may enhance its performance using FFPE samples by improving the detection limit., (© 2024 College of American Pathologists.)

Background: The transition of Australia's National Cervical Screening Program from cytology to a molecular test for human papillomavirus (HPV) (locally referred to as the 'Renewal'), including a longer five-year interval and older age at commencement, significantly impacted all sectors of program delivery. The Renewal had major implications for the roles and requirements of pathology laboratories providing services for the Program. This study aimed to understand the early impacts of the Renewal and its implementation on the pathology sector., Methods: Semi-structured qualitative interviews were conducted with key stakeholders (N = 49) involved in the STakeholder Opinions of Renewal Implementation and Experiences Study (STORIES), 11-20 months after the program transition. A subset of interviews (N = 24) that discussed the pathology sector were analysed using inductive thematic analysis., Results: Four overarching themes were identified: implementation enablers, challenges, missed opportunities, and possible improvements. Participants believed that the decision to transition to primary HPV screening was highly acceptable and evidence-based, but faced challenges due to impacts on laboratory infrastructure, resources, staffing, and finances. These challenges were compounded by unfamiliarity with new information technology (IT) systems and the new National Cancer Screening Register ('Register') not being fully functional by the date of the program transition. The limited availability of self-collection and lack of standardised fields in pathology forms were identified as missed opportunities to improve equity in the Program. To improve implementation processes, participants suggested increased pathology sector involvement in planning was needed, along with more timely and transparent communication from the Government, and clearer clinical management guidelines., Conclusion: The transition to primary HPV screening had a significant and multifaceted impact on the Australian pathology sector reflecting the magnitude and complexity of the Renewal. Strategies to support the pathology sector through effective change management, clear, timely, and transparent communication, as well as adequate funding sources will be critical for other countries planning to transition cervical screening programs., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Objective: Morbidity and mortality from coronavirus disease 2019 (COVID-19) have been significant among elderly residents of residential aged-care services (RACS). To prevent incursions of COVID-19 in RACS in Australia, visitors were banned and aged-care workers were encouraged to work at a single site. We conducted a review of case notes and a social network analysis to understand how workplace and social networks enabled the spread of severe acute respiratory coronavirus virus 2 (SARS-CoV-2) among RACS., Design: Retrospective outbreak review., Setting and Participants: Staff involved in COVID-19 outbreaks in RACS in Victoria, Australia, May-October 2020., Methods: The Victorian Department of Health COVID-19 case and contact data were reviewed to construct 2 social networks: (1) a work network connecting RACS through workers and (2) a household network connecting to RACS through households. Probable index cases were reviewed to estimate the number and size (number of resident cases and deaths) of outbreaks likely initiated by multisite work versus transmission via households., Results: Among 2,033 cases linked to an outbreak as staff, 91 (4.5%) were multisite staff cases. Forty-three outbreaks were attributed to multisite work and 35 were deemed potentially preventable had staff worked at a single site. In addition, 99 staff cases were linked to another RACS outbreak through their household contacts, and 21 outbreaks were attributed to staff-household transmission., Conclusions: Limiting worker mobility through single-site policies could reduce the chances of SARS-CoV-2 spreading from one RACS to another. However, initiatives that reduce the chance of transmission via household networks would also be needed.

Australia's cervical screening program transitioned from cytology to HPV-testing with genotyping for HPV16/18 in Dec'2017. We investigated whether program data could be used to monitor HPV vaccination program impact (commenced in 2007) on HPV16/18 prevalence and compared estimates with pre-vaccination benchmark prevalence. Pre-vaccination samples (2005-2008) (n = 1933; WHINURS), from 25 to 64-year-old women had been previously analysed with Linear Array (LA). Post-vaccination samples (2013-2014) (n = 2989; Compass pilot), from 25 to 64-year-old women, were analysed by cobas 4800 (cobas), and by LA for historical comparability. Age standardised pre-vaccination HPV16/18 prevalence was 4.85% (95%CI:3.81-5.89) by LA; post-vaccination estimates were 1.67% (95%CI:1.21-2.13%) by LA, 1.49% (95%CI:1.05-1.93%) by cobas, and 1.63% (95%CI:1.17-2.08%) for cobas and LA testing of non-16/18 cobas positives (cobas/LA). Age-standardised pre-vaccination oncogenic HPV prevalence was 15.70% (95%CI:13.79-17.60%) by LA; post-vaccination estimates were 9.06% (95%CI:8.02-10.09%) by LA, 8.47% (95%CI:7.47-9.47%) by cobas and cobas/LA. Standardised rate ratios between post-vs. pre-vaccination rates were significantly different for HPV16/18, non-16/18 HPV and oncogenic HPV: 0.34 (95%CI:0.23-0.50), 0.68 (95%CI:0.55-0.84) and 0.58 (95%CI:0.48-0.69), respectively. Additional strategies (LA for all cobas positives; combined cobas and LA results on all samples) had similar results. If a single method is applied consistently, it will provide important data on relative changes in HPV prevalence following vaccination., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)

Abstract: The Australian Paediatric Surveillance Unit (APSU) has been conducting surveillance of rare communicable and non-communicable conditions in children since its inception in 1993. In this report, the results are described of surveillance of ten communicable diseases (and complications) for 2021, including the numbers of cases and incidence estimates; demographics; clinical features; and management and short-term outcomes. The included diseases are: acute flaccid paralysis (AFP); congenital cytomegalovirus (CMV); neonatal herpes simplex virus (HSV) infection; paediatric human immunodeficiency virus (HIV) infection; perinatal exposure to HIV; severe complications from influenza; juvenile-onset respiratory papillomatosis (JoRRP); congenital rubella syndrome; congenital varicella syndrome; and neonatal varicella infection. In 2021, cases of JoRRP were reported to the APSU for the first time since 2017, indicating potential gaps in HPV vaccination. AFP surveillance by APSU again contributed to Australia achieving a minimum target incidence of one AFP case per 100,000 children aged < 15 years. There were no cases of children with severe complications of influenza. No cases of varicella or congenital rubella were reported; however, at-risk populations, especially young migrant and refugee women from countries without universal vaccination programs, need to be screened and prioritised for vaccination prior to pregnancy. Cases of perinatal exposure to HIV continue to increase; however, the rate of mother-to-child-transmission remains at low levels due to the use of effective intervention strategies. Case numbers of congenital CMV and neonatal HSV remain steady in the absence of vaccines, prompting the need for greater awareness and education, with recent calls for target screening of at-risk infants for congenital CMV., (© Commonwealth of Australia CC BY-NC-ND.)

Background: Human papillomavirus (HPV) vaccines were first licensed as a three-dose series. Two doses are now widely recommended in some age groups; there are data suggesting high efficacy with one dose. We updated a systematic literature review of HPV vaccine effectiveness by number of doses in observational studies., Methods: We searched Medline and Embase databases from January 1, 2007, through September 29, 2021. Data were extracted and summarized in a narrative synthesis. We also conducted quality assessments for bias due to selection, information, and confounding., Results: Overall, 35 studies were included; all except one were conducted within the context of a recommended three-dose schedule. Evaluations were in countries that used bivalent HPV vaccine (seven), quadrivalent HPV vaccine (27) or both (one). Nine evaluated effectiveness against HPV infection, ten anogenital warts, and 16 cervical abnormalities. All studies were judged to have moderate or serious risk of bias. The biases rated as serious would likely result in lower effectiveness with fewer doses. Investigators attempted to control for or stratify by potentially important variables, such as age at vaccination. Eight studies evaluated impact of buffer periods (lag time) for case counting and 10 evaluated different intervals between doses for two-dose vaccine recipients. Studies that stratified by vaccination age found higher effectiveness with younger age at vaccination, although differences were not all formally tested. Most studies found highest estimates of effectiveness with three doses; significant effectiveness was found among 28/29 studies that evaluated three doses, 19/29 that evaluated two doses, and 18/30 that evaluated one dose. Some studies that adjusted or stratified analyses by age at vaccination found similar effectiveness with three, two and one doses., Conclusion: Observational studies of HPV vaccine effectiveness have many biases. Studies examining persons vaccinated prior to sexual activity and using methods to reduce sources of bias are needed for valid effectiveness estimates., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. LM, MD, MJ, JMB, GO, ARK, and MB are members of the Single-Dose HPV vaccine evaluation consortium., (Published by Elsevier Ltd.)

Objectives: Previously, based on 6 months of follow-up, we showed that HPV self-sampling improved participation in cervical screening compared to a reminder letter for Pap testing for never- and under-screened women. Here, we report follow-up and related screening outcomes for women who participated in the initial self-sampling over two screening rounds., Setting: The randomised controlled trial was conducted in Australia., Methods: Never- and under-screened women were randomly allocated to the HPV self-sampling or the reminder for Pap test arm and followed at 6 and 36 months since the kits were first mailed., Results: The first round of HPV self-sampling kits were mailed from May-July 2014 to 12 572 women. After 36 months, 19% of never-screened and 9% of under-screened women returned a kit for HPV testing; 2.7% were HPV 16/18 and 5.8% non-16/18 HPV positive. Compliance with first round follow-up was 84% (95% CI: 77.1-89.5%). Non-compliant and cytology triage negative women were mailed another kit at 12 months. Compliance at 12-month follow-up was 59.3% (49.4 to 68.6%). Of 37 women with a 12-month repeat HPV, 70% were positive. Of women who tested negative for HPV in the first round (n = 1573), 25% attended regular screening in the next round and none had CIN2 + detected. The overall prevalence of CIN2 + was 8.5 per 1000 screened (4.8 to 13.9 per 1000)., Conclusion: While self-sampling can successfully engage women, compliance with repeat testing may require monitoring. The clinician-supported self-collection pathway now in use in Australia will likely improve women's engagement with follow-up.

Background: Australia has had significant successes in the prevention of cervical cancer. However, there is considerable scope for improving screening participation. In December 2017, Australia shifted from cytology to a human papillomavirus-based screening program as part of the renewed National Cervical Screening Program. This provided the opportunity to introduce a clinician-supported self-collection cervical screening pathway, which allows screening participants aged 30 years or more and who are under-screened or never-screened to screen via a self-collected human papillomavirus test., Objective: This study aimed to explore screening participant experiences of a clinician-supported self-collection cervical screening pathway., Methods: Interviews (n = 45) were conducted with participants who had used the clinician-supported self-collection cervical screening pathway in the Australian National Cervical Screening Program between December 2017 and April 2019. Interviews were analyzed using template analysis., Results: Under-screened and never-screened participants reported a variety of interrelated barriers to cervical screening due to the nature of the test. For these participants, self-collection was a preferable way to perform screening as it overcame various barriers, was easy to use and promoted a sense of empowerment. Participants reported that the role of their practitioner was influential in their decision to undertake cervical screening, and that the support and information provided was a key factor in their experiences of the self-collection pathway., Conclusion: Findings support the use of a clinician-supported model of care, as an alternative screening modality in Australia's National Cervical Screening Program. As more countries consider the move from a cytology to human papillomavirus-based cervical screening program, this model may assist in greater engagement of under-screened participants.

Objectives: To evaluate the implementation and acceptability of the self-collection cervical screening pathway since commencement of the renewed National Cervical Screening Program (rNCSP), from the perspectives of screening participants and primary care practitioners., Design, Setting, Participants: Qualitative study; individual semi-structured interviews with 45 screening participants and 18 primary care practitioners in Victoria who had engaged with the self-collection pathway during the first 17 months of the rNCSP (1 December 2017 - 30 April 2019)., Results: The self-collection pathway was highly acceptable as an alternative cervical screening pathway for most participating screening participants and practitioners. Some screening participants indicated that they would not have been screened had the pathway not been available. Acceptability was lower among those who had tested positive for HPV types not 16/18, a result that requires additional testing of a clinician-collected cervical sample. Use of the self-collection pathway is driven more by practitioners than their patients. Interpretations of the self-collection guidelines varied between practices. Barriers to expanding promotion of the pathway by practitioners included difficulties with identifying eligible participants., Conclusions: Increasing the accessibility of the self-collection pathway to under- and never screened women could reduce inequities in cervical cancer outcomes for those not participating in the main screening pathway. Practitioners should be provided resources to integrate self-collection into routine practice and to efficiently implement the entire self-collection pathway, in order to maximise its use and to optimise the experience for screening participants., (© 2021 AMPCo Pty Ltd.)

Background: Initially, three-dose schedules were recommended for vaccines against human papillomavirus (HPV); subsequently recommendations have been updated to a schedule of two doses delivered at least six (minimum five) months apart for those aged <15 years at dose 1. We aimed to re-estimate effective HPV vaccination coverage in Australia, considering reduced-dose schedules and possible one-dose effectiveness. We also aimed to identify which of the three school visits was most commonly missed amongst two-dose only recipients, to inform optimal timing of visits., Methods: National vaccination register data were used to estimate: i) vaccination coverage at December 2017, either with a complete course (three or two sufficiently-spaced doses (>151 days apart)), or at least one dose; ii) for each birth cohort offered vaccination, the percentage of the initially targeted cohort with a complete course, or at least one dose (reflecting uptake at the time the vaccine was offered); and iii) among two-dose only recipients, the percentage who missed each of three school visits., Results: Including those with two sufficiently-spaced doses increased end-2017 coverage by 1.3-2.8% points in those vaccinated at school. Including those with at least one dose increased coverage further, by 6.5-9.5% points, mostly due to including those receiving multiple too-closely-spaced doses. One-dose coverage reached 90.9% and 86.9% in females and males respectively born in 2002. Among those vaccinated at school who received only two doses, it was much more common to miss the first (31.0% females; 32.5% males) or the third visit in the school year (54.6% females; 48.6% males) than the second (14.1% females; 18.8% males)., Conclusions: Including those with two sufficiently-spaced doses has a very modest impact on HPV vaccine coverage in Australia. If receiving at least one dose offers substantial protection, these data suggest that the school-based program is now achieving close to 90% coverage on this measure., (Copyright © 2021. Published by Elsevier B.V.)

The Australian Paediatric Surveillance Unit (APSU) has been prospectively collecting national data on rare childhood conditions since 1993, with monthly reporting of cases by paediatricians. In this report we describe annual results from studies for ten communicable diseases and complications of communicable diseases that were conducted using APSU surveillance in 2019 and place these in an historic context. Results are reported on acute flaccid paralysis, congenital cytomegalovirus infection, neonatal herpes simplex virus infection, perinatal exposure to HIV, paediatric HIV infection, severe complications of seasonal influenza, juvenile onset recurrent respiratory papillomatosis (JoRRP), congenital rubella syndrome, congenital varicella syndrome and neonatal varicella infection. APSU provides rich clinical data to complement data collected from other surveillance systems and to improve understanding and response to rare childhood infections., (© Commonwealth of Australia CC BY-NC-ND.)

Aim: Prophylactic human papillomavirus (HPV) vaccines are highly effective at preventing pre-cancerous cervical lesions when given in a three-dose schedule. Some post-hoc trial data suggest that one dose prevents HPV infection. If one dose could prevent pre-cancerous cervical lesions, then global cervical cancer prevention would be greatly facilitated. We assessed the effectiveness of quadrivalent HPV vaccine by number of doses against cervical intraepithelial neoplasia (CIN) 2 or 3/adenocarcinoma-in-situ (AIS)/cancer in Australia up to seven years post vaccination., Methods: We linked registry data from all 8 jurisdictional cervical screening registers, with the national HPV vaccination register, death index and cancer registers for all Australian women aged 15 or under when eligible for vaccine who screened between April 2007 (when vaccination commenced) and 31 December 2014. We performed Cox proportional hazard regression, adjusted a priori for age, socioeconomic status, and area of residence, to estimate hazard ratios of histologically confirmed CIN2/CIN3/AIS/cancer., Results: We included 250,648 women: 48,845 (19·5%) unvaccinated, 174,995 (69·8%) had received three doses, 18,190 (7·3%) two doses and 8,618 (3·4%) one dose. The adjusted hazard ratio was significantly lower for all dose groups compared to unvaccinated women (1 dose 0·65 (95%CI 0·52-0·81), 2 doses 0·61 (0·52-0·72) and 3 doses 0·59 (0·54-0·65).) With adjustment for age at vaccination amongst the vaccinated group, the adjusted hazard ratios for one dose and two dose recipients were comparable to three dose recipients (one dose 1.01 (95%CI 0.81-1.26), two doses 1.00 (0.85-1.17).) Multiple sensitivity analyses, including use of different dose assignment methods, produced consistent findings. Comparison with a historical cohort of age matched women showed that the result was not due to herd protection alone., Conclusions: One dose had comparable effectiveness as two or three doses in preventing high-grade disease in a high coverage setting. These findings support the hypothesis that one dose vaccination may be a viable strategy when working towards the global elimination of cervical cancer., (Copyright © 2019. Published by Elsevier B.V.)

Objective: To estimate human papillomavirus (HPV) vaccination coverage and course completion rates for Indigenous adolescents in four Australian states and territories., Participants, Setting: Adolescents who were 12 years old in 2015 and received the quadrivalent HPV vaccine (three doses: 0, 2, 6 months) as part of the National HPV Vaccination Program in 2015 or 2016 in New South Wales, Queensland, the Northern Territory, or the Australian Capital Territory., Main Outcome Measures: Estimated HPV vaccination coverage by dose and by Indigenous status and sex, based on National HPV Vaccination Program Register data; vaccination course completion rates (proportion of dose 1 recipients who received dose 3) for 12-year-olds vaccinated during 2013-2016, by sex, jurisdiction, and Indigenous status., Results: Dose 1 coverage exceeded 80% for all Indigenous status/jurisdiction/sex groups (range, 83.3-97.7%). Coverage was similar for Indigenous and non-Indigenous girls in Queensland (87.3% v 87.0%), lower for Indigenous girls in the ACT (88.7% v 97.7%) and the NT (91.1% v 97.0%), and higher in NSW (95.9% v 89.9%); it was similar for Indigenous and non-Indigenous boys in all jurisdictions except the NT (88.6% v 96.3%). Dose 3 coverage (range, 61.2-87.7%) was markedly lower for Indigenous than non-Indigenous 12-year-olds in all jurisdictions, except for girls in NSW (82.6% v 83.6%)., Conclusion: HPV vaccine coverage is high, but course completion is generally lower for Indigenous adolescents. Strategies for improving completion rates for Indigenous Australians are needed to end the higher burden of cervical cancer among Indigenous than non-Indigenous women., (© 2019 AMPCo Pty Ltd.)

Objective: Cervical cancer mortality has halved in Australia since the national cervical screening program began in 1991, but elevated mortality rates persist for Aboriginal and Torres Strait Islander women (referred to as Aboriginal women in this report). We investigated differences by Aboriginal status in abnormality rates predicted by cervical cytology and confirmed by histological diagnoses among screened women., Methods: Using record linkage between cervical screening registry and public hospital records in South Australia, we obtained Aboriginal status of women aged 20-69 for 1993-2016 (this was not recorded by the registry). Differences in cytological abnormalities were investigated by Aboriginal status, using relative risk ratios from mixed effect multinomial logistic regression modelling. Odds ratios were calculated for histological high grade results for Aboriginal compared with non-Aboriginal women., Results: Of 1,676,141 linkable cytology tests, 5.8% were abnormal. Abnormal results were more common for women who were younger, never married, and living in a major city or socioeconomically disadvantaged area. After adjusting for these factors and numbers of screening episodes, the relative risk of a low grade cytological abnormality compared with a normal test was 14% (95% confidence interval 5-24%) higher, and the relative risk of a high grade cytological abnormality was 61% (95% confidence interval 44-79%) higher, for Aboriginal women. The adjusted odds ratio of a histological high grade was 76% (95% confidence interval 46-113%) higher., Conclusions: Ensuring that screen-detected abnormalities are followed up in a timely way by culturally acceptable services is important for reducing differences in cervical cancer rates between Aboriginal and non-Aboriginal women.

Australia's transition to primary human papillomavirus (HPV) based cervical screening, has for the first time, provided a passive mechanism for monitoring the impact of vaccination on infection prevalence among women attending screening. We assessed oncogenic HPV prevalence by single year of age in the first 7  months of the program, using data collected from a large screening laboratory in Victoria, Australia, which is routinely screening using cobas 4800, cobas 6800 and Seegene assays. Among 116,052 primary screening samples from women aged 25-74, 9.25% (95%CI: 9.09-9.42%) had oncogenic HPV detected: 2.14% (95%CI: 2.05-2.22%) were 16/18 positive and 7.12% (95%CI: 6.97-7.27%) were positive for only non-16/18 HPV. Prevalence peaked at age 25-29 then decreased with age, but this was driven by non-16/18 types. HPV16/18 prevalence remained low and flat across ages, contrasting with pre-vaccination epidemiology when HPV16/18 peaked in young women. HPV-based screening can precisely monitor HPV prevalence., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Background: In 2007, Australia was one of the first countries to introduce a national human papillomavirus (HPV) vaccination programme, and it has since achieved high vaccination coverage across both sexes. In December, 2017, organised cervical screening in Australia transitioned from cytology-based screening every 2 years for women aged from 18-20 years to 69 years, to primary HPV testing every 5 years for women aged 25-69 years and exit testing for women aged 70-74 years. We aimed to identify the earliest years in which the annual age-standardised incidence of cervical cancer in Australia (which is currently seven cases per 100 000 women) could decrease below two annual thresholds that could be considered to be potential elimination thresholds: a rare cancer threshold (six new cases per 100 000 women) or a lower threshold (four new cases per 100 000 women), since Australia is likely to be one of the first countries to reach these benchmarks., Methods: In this modelling study, we used Policy1-Cervix-an extensively validated dynamic model of HPV vaccination, natural history, and cervical screening-to estimate the age-standardised incidence of cervical cancer in Australia from 2015 to 2100. We incorporated age-specific coverage of the Australian National HPV Vaccination Program in girls, including the catch-up programme, and the inclusion of boys into the vaccine programme from 2013, and a change from the quadrivalent to the nonavalent vaccine from 2018. We also modelled the effects of the transition to primary HPV screening. We considered two scenarios for future screening recommendations regarding the cohorts who will be and who have been offered the nonavalent vaccine: either that HPV screening every 5 years continues, or that no screening would be offered to these women., Findings: We estimate that, in Australia, the age-standardised annual incidence of cervical cancer will decrease to fewer than six new cases per 100 000 women by 2020 (range 2018-22), and to fewer than four new cases per 100 000 women by 2028 (2021-35). The precise year of attaining these rates is dependent on the population used for age-standardisation, HPV screening behaviour and test characteristics, the incremental effects of vaccination of men on herd immunity in women, and assumptions about the future frequency of benign hysterectomies. By 2066 (2054-77), the annual incidence of cervical cancer will decrease and remain at fewer than one case per 100 000 women if screening for HPV every 5 years continues for cohorts who have been offered the nonavalent vaccine, or fewer than three cases per 100 000 women if these cohorts are not screened. Cervical cancer mortality is estimated to decrease to less than an age-standardised annual rate of one death per 100 000 women by 2034 (2025-47), even if future screening is only offered to older cohorts that were not offered the nonavalent vaccine., Interpretation: If high-coverage vaccination and screening is maintained, at an elimination threshold of four new cases per 100 000 women annually, cervical cancer could be considered to be eliminated as a public health problem in Australia within the next 20 years. However, screening and vaccination initiatives would need to be maintained thereafter to maintain very low cervical cancer incidence and mortality rates., Funding: National Health and Medical Research Council (Australia)., (Copyright © 2019 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC-BY-NC-ND 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

Background: A National human papilloma virus (HPV) Vaccination Programme for the prevention of HPV infection and associated disease using the quadrivalent HPV vaccine (4vHPV) has been funded and implemented in Australia since 2007, initially for girls only and extended to boys in 2013, with uptake rates among the highest observed worldwide., Aim: We report on the impact of this national programme on HPV prevalence and associated disease burden and estimate the potential impact of adopting a nonavalent HPV (9vHPV) vaccine., Methods: We performed a non-systematic literature review of studies measuring the burden of HPV-associated disease and infection in Australia before and after introduction of HPV vaccination. We also included key national reports with estimates of HPV-related disease burden., Results: Substantial declines in high-grade cervical disease and genital warts among vaccine-eligible women have been observed. Reductions in genital warts incidence and HPV prevalence among heterosexual men of similar age were observed before introduction of the male vaccination programme, indicating a substantial herd effect. 9vHPV vaccine is expected to prevent up to 90% of cervical and 96% of anal cancers. Of an estimated 1,544 HPV-associated cancers in 2012, 1,242 would have been preventable by the 4vHPV vaccine and an additional 187 anogenital cancers by the 9vHPV vaccine., Conclusions: Vaccination using 4vHPV vaccine has had a large demonstrable impact on HPV-related disease in Australia. A switch to 9vHPV could further reduce the HPV-associated cancer burden. With continued high coverage among both males and females, elimination of vaccine-type HPV disease seems achievable in Australia.

Background: Australia has included quadrivalent human papillomavirus (HPV) vaccination in its national program since 2007. Significant declines have been observed in the incidence of HPV infection, genital warts and high-grade cervical lesions. In 2018, the program changed to a nonavalent HPV vaccine administered over a routine two-dose schedule for the target cohort of adolescents aged 12-13 years., Objective: The aim of this article is to provide an overview of the nonavalent HPV vaccine, the rationale for its use and expected outcomes, and to review the updated dose scheduling requirements for HPV vaccines., Discussion: The nonavalent HPV vaccine will broaden the impact of HPV vaccination, primarily against cervical cancer and pre-cancer. A two-dose schedule with an interval of 6-12 months between doses is appropriate for those aged ≤14 years at the time of first dose. Older individuals and those who are immunocompromised should continue to receive the three-dose schedule at zero, two and six months.

This 8th annual immunisation coverage report shows data for 2014 derived from the Australian Childhood Immunisation Register and the National Human Papillomavirus Vaccination Program Register. This report includes coverage data for 'fully immunised' and by individual vaccines at standard age milestones and timeliness of receipt at earlier ages according to Indigenous status. Overall, 'fully immunised' coverage has been mostly stable at the 12- and 24-month age milestones since late 2003, but at 60 months of age, it has increased by more than 10 percentage points since 2009. As in previous years, coverage for 'fully immunised' at 12 months of age among Indigenous children was 3.7% lower than for non-Indigenous children overall, varying from 6.9 percentage points in Western Australia to 0.3 of a percentage point in the Australian Capital Territory. In 2014, 73.4% of Australian females aged 15 years had 3 documented doses of human papillomavirus vaccine (jurisdictional range 67.7% to 77.4%), and 82.7% had at least 1 dose, compared with 71.4% and 81.5%, respectively, in 2013. The disparity in on-time vaccination between Indigenous and non-Indigenous children in 2014 diminished progressively from 20.2% for vaccines due by 12 months to 11.5% for those due by 24 months and 3.0% at 60 months of age.

Objectives: To investigate time to follow-up (clinical investigation) for Indigenous and non-Indigenous women in Queensland after a high grade abnormality (HGA) being detected by Pap smear., Design, Setting, Participants: Population-based retrospective cohort analysis of linked data from the Queensland Pap Smear Register (PSR), the Queensland Hospital Admitted Patient Data Collection, and the Queensland Cancer Registry. 34 980 women aged 20-68 years (including 1592 Indigenous women) with their first HGA Pap smear result recorded on the PSR (index smear) during 2000-2009 were included and followed to the end of 2010., Main Outcome Measures: Time from the index smear to clinical investigation (histology test or cancer diagnosis date), censored at 12 months., Results: The proportion of women who had a clinical investigation within 2 months of a HGA finding was lower for Indigenous (34.1%; 95% CI, 31.8-36.4%) than for non-Indigenous women (46.5%; 95% CI, 46.0-47.0%; unadjusted incidence rate ratio [IRR], 0.65; 95% CI, 0.60-0.71). This difference remained after adjusting for place of residence, area-level disadvantage, and age group (adjusted IRR, 0.74; 95% CI, 0.68-0.81). However, Indigenous women who had not been followed up within 2 months were subsequently more likely to have a clinical investigation than non-Indigenous women (adjusted IRR for 2-4 month interval, 1.21; 95% CI, 1.08-1.36); by 6 months, a similar proportion of Indigenous (62.2%; 95% CI, 59.8-64.6%) and non-Indigenous women (62.8%; 95% CI, 62.2-63.3%) had been followed up., Conclusions: Prompt follow-up after a HGA Pap smear finding needs to improve for Indigenous women. Nevertheless, slow follow-up is a smaller contributor to their higher cervical cancer incidence and mortality than their lower participation in cervical screening.

Objectives/hypothesis: To estimate the prevalence of juvenile onset recurrent respiratory papillomatosis (RRP) in Australia, describe its epidemiological profile, and assess the positive predictive value of International Classification of Disease, 10th revision (ICD-10) code D14.1 (benign neoplasm of larynx) in children for hospitalization due to RRP., Study Design: Retrospective case series., Methods: Retrospective case review undertaken at the three tertiary pediatric hospitals in New South Wales (Australia's largest state), by reviewing medical records of patients aged 0 to 16 years admitted during 2000-2009 containing the ICD-10 Australian modification code D14.1 or other possible disease (D14.2-4, D14.3, D14.4) and RRP-related procedure codes. For RRP diagnoses, we recorded treatment dates, length of stay, extent of disease, and surgical and adjuvant treatments. The positive predictive value (PPV) of code D14.1 and median number of hospitalizations per year were applied to national hospital separations data from 2000/2001 to 2012/2013 to estimate disease prevalence., Results: We identified 30 cases of RRP using code D14.1, which had a PPV of 98.1%, with no further cases identified using other codes. Fifty-seven percent of cases were female, median age of onset was 36 months, and median treatment duration was 36 months (mean = 40 months, range = 1-118). There was one patient death. Between 2000 and 2013, the estimated national prevalence rate was 0.81 per 100,000 aged < 15 years, peaking at age 5 to 9 years (1.1 per 100,000)., Conclusions: RRP prevalence can be monitored after human papillomavirus vaccination programs using routine hospital data., Level of Evidence: 4 Laryngoscope, 126:2827-2832, 2016., (© 2016 The American Laryngological, Rhinological and Otological Society, Inc.)

We analyzed human papillomavirus (HPV) prevalences during prevaccination and postvaccination periods to consider possible changes in nonvaccine HPV genotypes after introduction of vaccines that confer protection against 2 high-risk types, HPV16 and HPV18. Our meta-analysis included 9 studies with data for 13,886 girls and women ≤19 years of age and 23,340 women 20-24 years of age. We found evidence of cross-protection for HPV31 among the younger age group after vaccine introduction but little evidence for reductions of HPV33 and HPV45. For the group this same age group, we also found slight increases in 2 nonvaccine high-risk HPV types (HPV39 and HPV52) and in 2 possible high-risk types (HPV53 and HPV73). However, results between age groups and vaccines used were inconsistent, and the increases had possible alternative explanations; consequently, these data provided no clear evidence for type replacement. Continued monitoring of these HPV genotypes is important.

This review is one of two complementary reviews that have been prepared in the framework of the Eurogin Roadmap 2015 to evaluate how knowledge about HPV is changing practices in HPV infection and disease control through vaccination and screening. In this review of HPV vaccine knowledge, we present the most significant findings of the past year which have contributed to our knowledge of the two HPV prophylactic vaccines currently in widespread use and about the recently licensed nonavalent HPV vaccine. Whereas anal cancer is dealt with in the companion mini-review on screening, we also review here the rapidly evolving evidence regarding HPV-associated head and neck cancer and priority research areas., (© 2016 UICC.)

We conducted a randomized controlled trial to determine whether HPV self-sampling increases participation in cervical screening by never- and under-screened (not screened in past 5 years) women when compared with a reminder letter for a Pap test. Never- or under-screened Victorian women aged 30-69 years, not pregnant and with no prior hysterectomy were eligible. Within each stratum (never-screened and under-screened), we randomly allocated 7,140 women to self-sampling and 1,020 to Pap test reminders. The self-sampling kit comprised a nylon tipped flocked swab enclosed in a dry plastic tube. The primary outcome was participation, as indicated by returning a swab or undergoing a Pap test; the secondary outcome, for women in the self-sampling arm with a positive HPV test, was undergoing appropriate clinical investigation. The Roche Cobas® 4800 test was used to measure presence of HPV DNA. Participation was higher for the self-sampling arm: 20.3 versus 6.0% for never-screened women (absolute difference 14.4%, 95% CI: 12.6-16.1%, p < 0.001) and 11.5 versus 6.4% for under-screened women (difference 5.1%, 95% CI: 3.4-6.8%, p < 0.001). Of the 1,649 women who returned a swab, 45 (2.7%) were positive for HPV16/18 and 95 (5.8%) were positive for other high-risk HPV types. Within 6 months, 28 (62.2%) women positive for HPV16/18 had colposcopy as recommended and nine (20%) had cytology only. Of women positive for other high-risk HPV types, 78 (82.1%) had a Pap test as recommended. HPV self-sampling improves participation in cervical screening for never- and under-screened women and most women with HPV detected have appropriate clinical investigation., (© 2016 UICC.)

Background: The Australian National Cervical Screening Program, introduced more than 20 years ago, does not record the Indigenous status of screening participants. This article reports the first population-based estimates of participation in cervical screening for Indigenous and non-Indigenous Australian women., Methods: This was a retrospective, population-based study of 1,334,795 female Queensland residents, aged 20 to 69 years, who participated in cervical screening from 2000 to 2011; 26,829 were identified as Indigenous through linkage to hospitalization records. Participation rates were calculated as the number of women screened divided by the average estimated resident population, with adjustments made for hysterectomies, for each 2-, 3-, and 5-year screening period. Multivariate logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs), which were adjusted for age group, place of residence, and socioeconomic disadvantage., Results: In 2010-2011, the 2-year participation rate was 55.7% (95% CI, 55.6%-55.9%) for non-Indigenous women and 33.5% (95% CI, 32.9%-34.1%) for Indigenous women; this represented a decrease from 2000-2001 (57.7% [95% CI, 57.6%-57.9%] and 35.3% [95% CI, 34.5%-36.1%], respectively). The difference between Indigenous and non-Indigenous women was greatest for those aged 45 to 49 years. The 3- and 5-year participation rates were higher within both groups, and the absolute differences between the 2 groups were larger. Significant interactions between the Indigenous status and the place of residence and socioeconomic disadvantage highlight that the Indigenous/non-Indigenous differential was evident in all places of residence except for very remote areas (OR, 0.99; 95% CI, 0.95-1.02) and was greatest in the most affluent areas (OR, 0.26; 95% CI, 0.24-0.27)., Conclusions: Indigenous Australian women participate less than non-Indigenous women, and this gap has not closed. These results provide important benchmarks for the new Australian cervical screening program commencing in 2017, which will provide opportunities to reduce inequities for Indigenous women and address longstanding data deficiencies in the collection of the Indigenous status. Cancer 2016;122:1560-9. © 2016 The Authors. Cancer published by Wiley Periodicals, Inc. on behalf of American Cancer Society., (© 2016 The Authors. Cancer published by Wiley Periodicals, Inc. on behalf of American Cancer Society.)

Indigenous Australian women have much higher incidence of cervical cancer compared to non-Indigenous women. Despite an organised cervical screening program introduced 25 years ago, a paucity of Indigenous-identified data in Pap Smear Registers remains. Prevalence of cervical abnormalities detected among the screened Indigenous population has not previously been reported. We conducted a retrospective cohort study of population-based linked health records for 1,334,795 female Queensland residents aged 20-69 years who had one or more Pap smears during 2000-2011; from linked hospital records 23,483 were identified as Indigenous. Prevalence was calculated separately for Indigenous and non-Indigenous women, for cytology-detected low-grade (cLGA) and high-grade abnormalities (cHGA), and histologically confirmed high-grade abnormalities (hHGA). Odds ratios (OR) were estimated from logistic regression analysis. In 2010-2011 the prevalence of hHGA among Indigenous women (16.6 per 1000 women screened, 95% confidence interval [CI] 14.6-18.9) was twice that of non-Indigenous women (7.5 per 1000 women screened, CI 7.3-7.7). Adjusted for age, area-level disadvantage and place of residence, Indigenous women had higher prevalence of cLGA (OR 1.4, CI 1.3-1.4), cHGA (OR 2.2, CI 2.1-2.3) and hHGA (OR 2.0, CI 1.9-2.1). Our findings show that Indigenous women recorded on the Pap Smear Register have much higher prevalence for cLGA, cHGA and hHGA compared to non-Indigenous women. The renewed cervical screening program, to be implemented in 2017, offers opportunities to reduce the burden of abnormalities and invasive cancer among Indigenous women and address long-standing data deficiencies.

Unlabelled: Background Adult Australian women aged 18 to 26 years were offered human papillomavirus (HPV) vaccine in a mass catch up campaign between 2007 and 2009. Not all doses administered were notified to Australia's HPV vaccine register and not all young women commenced or completed the vaccine course., Methods: We surveyed vaccine age-eligible women as part of the Victorian Population Health Survey 2011-2012, a population based telephone survey, to ascertain self-reported vaccine uptake and reasons for non-vaccination or non-completion of vaccination among young women resident in the state of Victoria, Australia., Results: Among 956 women surveyed, 62.3 per cent (57.8-66.6%) had been vaccinated against HPV and coverage with three doses was estimated at 53.7 per cent (49.1-58.2%). These estimates are higher than register-based estimates for the same cohort, which were 57.8 per cent and 37.2 per cent respectively. A lack of awareness about needing three doses and simply forgetting, rather than fear or experience of side effects, were the most common reasons for failure to complete all three doses. Among women who were not vaccinated, the most frequent reasons were not knowing the vaccine was available, perceiving they were too old to benefit, or not being resident in Australia at the time., Conclusions: It is likely that at least half of Victoria's young women were vaccinated during the catch-up program. This high level of coverage is likely to explain the marked reductions in HPV infection, genital warts and cervical disease already observed in young women in Victoria.

Objective: To evaluate the feasibility and reliability of record linkage of existing population-based data sets to determine Indigenous status among women receiving Pap smears. This method may allow for the first ever population measure of Australian Indigenous women's cervical screening participation rates., Setting/participants: A linked data set of women aged 20-69 in the Queensland Pap Smear Register (PSR; 1999-2011) and Queensland Cancer Registry (QCR; 1997-2010) formed the Initial Study Cohort. Two extracts (1995-2011) were taken from Queensland public hospitals data (Queensland Hospital Admitted Patient Data Collection, QHAPDC) for women, aged 20-69, who had ever been identified as Indigenous (extract 1) and had a diagnosis or procedure code relating to cervical cancer (extract 2). The Initial Study Cohort was linked to extract 1, and women with cervical cancer in the initial cohort were linked to extract 2., Outcome Measures: The proportion of women in the Initial Cohort who linked with the extracts (true -pairs) is reported, as well as the proportion of potential pairs that required clerical review. After assigning Indigenous status from QHAPDC to the PSR, the proportion of women identified as Indigenous was calculated using 4 algorithms, and compared., Results: There were 28,872 women (2.1%) from the Initial Study Cohort who matched to an ever Indigenous record in extract 1 (n=76,831). Women with cervical cancer in the Initial Study Cohort linked to 1385 (71%) records in extract 2. The proportion of Indigenous women ranged from 2.00% to 2.08% when using different algorithms to define Indigenous status. The Final Study Cohort included 1,372,823 women (PSR n=1,374,401; QCR n=1955), and 5,062,118 records., Conclusions: Indigenous status in Queensland cervical screening data was successfully ascertained through record linkage, allowing for the crucial assessment of the current cervical screening programme for Indigenous women. Our study highlights the need to include Indigenous status on Pap smear request and report forms in any renewed and redesigned cervical screening programme in Australia., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/)

Background: Increasing cervical screening coverage by reaching inadequately screened groups is essential for improving the effectiveness of cervical screening programs. Offering HPV self-sampling to women who are never or under-screened can improve screening participation, however participation varies widely between settings. Information on women's experience with self-sampling and preferences for future self-sampling screening is essential for programs to optimize participation., Methods: The survey was conducted as part of a larger trial ("iPap") investigating the effect of HPV self-sampling on participation of never and under-screened women in Victoria, Australia. Questionnaires were mailed to a) most women who participated in the self-sampling to document their experience with and preference for self-sampling in future, and b) a sample of the women who did not participate asking reasons for non-participation and suggestions for enabling participation. Reasons for not having a previous Pap test were also explored., Results: About half the women who collected a self sample for the iPap trial returned the subsequent questionnaire (746/1521). Common reasons for not having cervical screening were that having Pap test performed by a doctor was embarrassing (18 %), not having the time (14 %), or that a Pap test was painful and uncomfortable (11 %). Most (94 %) found the home-based self-sampling less embarrassing, less uncomfortable (90 %) and more convenient (98%) compared with their last Pap test experience (if they had one); however, many were unsure about the test accuracy (57 %). Women who self-sampled thought the instructions were clear (98 %), it was easy to use the swab (95 %), and were generally confident that they did the test correctly (81 %). Most preferred to take the self-sample at home in the future (88 %) because it was simple and did not require a doctor's appointment. Few women (126/1946, 7 %) who did not return a self-sample in the iPap trial returned the questionnaire. Their main reason for not screening was having had a hysterectomy., Conclusions: Home-based self-sampling can overcome emotional and practical barriers to Pap test and increase participation in cervical screening despite some women's concerns about test accuracy. Mailing to eligible women and assuring women about test accuracy could further optimize participation in screening.

Background: The National Human Papillomavirus (HPV) Vaccination Program in Australia commenced in 2007 for females and in 2013 for males, using the quadrivalent HPV vaccine (HPV 6,11,16,18). Thus far, we have demonstrated very substantial reductions in genital warts and in the prevalence of HPV among young Australian women, providing early evidence for the success of this public health initiative. Australia has a long history of school-based vaccination programs for adolescents, with comparatively high coverage. However, it is not clear what factors promote success in a school vaccination program. The HPV.edu study aims to examine: 1) student knowledge about HPV vaccination; 2) psycho-social outcomes and 3) vaccination uptake., Methods/design: HPV.edu is a cluster randomised trial of a complex intervention in schools aiming to recruit 40 schools with year-8 enrolments above 100 students (approximately 4400 students). The schools will be stratified by Government, Catholic, and Independent sectors and geographical location, with up to 20 schools recruited in each of two states, Western Australia (WA) and South Australia (SA), and randomly allocated to intervention or control (usual practice). Intervention schools will receive the complex intervention which includes an adolescent intervention (education and distraction); a decisional support tool for parents and adolescents and logistical strategies (consent form returns strategies, in-school mop-up vaccination and vaccination-day guidelines). Careful process evaluation including an embedded qualitative evaluation will be undertaken to explore in depth possible mechanisms for any observed effect of the intervention on primary and secondary outcomes., Discussion: This study is the first to evaluate the relative effectiveness of various strategies to promote best practice in school-based vaccination against HPV. The study aims to improve vaccination-related psychosocial outcomes, including adolescent knowledge and attitudes, decision-making involvement, self-efficacy, and to reduce fear and anxiety. The study also aims to improve school vaccination program logistics including reduction in time spent vaccinating adolescents and increased number of consent forms returned (regardless of decision). Less anxiety in adolescents will likely promote more efficient vaccination, which will be more acceptable to teachers, nurses and parents. Through these interventions, it is hoped that vaccination uptake will be increased., Trial Registration: Australian and New Zealand Clinical Trials Registry, ACTRN12614000404628 , 14.04.2014.