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Background: WHO recommends human papillomavirus (HPV) testing and same-day treatment for cervical screening in low-income and middle-income countries (LMICs); however, few published data exist on the validity of the strategy. We aimed to evaluate the clinical performance, treatment completion rates, adverse events profile, and acceptability of a fully integrated strategy, comprising point-of-care HPV DNA testing of self-collected specimens and same-day thermal ablation, for screening of cervical cancer in women in Papua New Guinea., Methods: HPV-STAT was a large-scale, prospective, single-arm intervention trial conducted at two clinical sites in Papua New Guinea. Cervical screening clinics with an on-site consultant gynaecologist were selected in consultation with national and provincial health authorities, church health services, and local stakeholders. Eligible participants were women aged 30-59 years attending cervical screening services at the two clinics, who were willing to comply with study procedures and able to provide written informed consent. Women self-collected vaginal specimens for point-of-care GeneXpert testing (Cepheid, Sunnyvale, CA, USA) for oncogenic HPV types. Women testing positive for HPV underwent pelvic examination followed by same-day thermal ablation or referral for gynaecology review. All HPV-positive women and a 15% random sample of HPV-negative women provided a clinician-collected cervical specimen for liquid-based cytology. The primary outcome was clinical performance (ie, sensitivity, specificity, positive predictive value [PPV], and negative predictive value [NPV]) of the strategy for the detection of high-grade squamous intraepithelial lesion (HSIL) or worse. This trial is registered with ISRCTN, ISRCTN13476702., Findings: Between June 5, 2018, and Jan 6, 2020, we recruited 4285 women, 3638 (84·9%) of whom tested negative for HPV and 647 (15·1%) tested positive for one or more oncogenic HPV type. Sensitivity of the algorithm to detect HSIL or worse was 85·4% (95% CI 81·0-89·6), with specificity 89·6% (88·6-90·6), PPV 35·2% (31·6-39·0), and NPV 98·9% (98·6-99·2). Among HPV-positive women, 602 (93·0%) received same-day thermal ablation and 42 (6·5%) were referred for gynaecology review, 37 (88·1%) of whom attended. Acceptability was high among both HPV-positive and HPV-negative women. Among the 329 HPV-positive women who attended a 3-month follow-up visit, 51 (15·5%) reported mild adverse symptoms that resolved in all cases by the follow-up visit. There were no serious adverse events., Interpretation: We conducted the first real-world evaluation of a fully integrated point-of-care HPV self-collect, test, and treat strategy for same-day cervical screening in a LMIC and found it to be effective, acceptable, and safe when implemented at scale in primary health-care facilities in Papua New Guinea. Our findings support the introduction and scale-up of HPV screening and treatment for the control and elimination of cervical cancer in LMICs, as recommended by WHO., Funding: Australian National Health and Medical Research Council., Competing Interests: Declaration of interests The Papua New Guinea Institute of Medical Research (AJBV, AK-H, JG, JB, GM, and PJT) and the Kirby Institute, UNSW Sydney (AJBV, SGB, AK-H, HW, RG, and JMK) have received subsidised test kits for research from Cepheid. VCS Foundation (MS, JMLB, and GT) has received donated test kits for research from Roche, Abbott, Seegene, Cepheid, AusDiagnostics, and Becton Dickinson. AJBV, MS, and KC jointly lead the Elimination of Cervical Cancer in the Western Pacific programme 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 Merck HPV Global Advisory Board and has led investigator-initiated grants from Merck on HPV in young women. All other authors declare no competing interests. All authors declare that neither they or their institutions have received direct funding from industry for this or any other research project., (Copyright © 2022 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

Background: Despite prophylactic human papillomavirus (HPV) vaccination being a safe, effective and cost-effective public health intervention for the prevention of cervical cancer, the HPV vaccine is not actively recommended or promoted by the Ministry of Health Labour and Welfare in Japan. With already very low levels of cervical screening below 30%, and vaccination levels that are below levels that award any population effect at 0.3% of the eligible population, cervical cancer mortality is higher than other similar high-income countries at 4.4/100,000 (2900) deaths per year in 2015. There is limited population-based or nationally representative data for HPV genotype distribution in Japan, thus making an assessment of the burden of vaccine-preventable cervical cancer difficult. Therefore, this systematic review and meta-analysis aims to determine the HPV genotype prevalence and age distribution of HPV infection in women with a cytological or histological diagnosis of normal through cervical cancer in Japan. We anticipate this information will guide and enhance programme interventions to reduce vaccine-preventable cervical cancer mortality in Japan., Methods: PubMed, Embase and the Japan Medical Abstract Society Database will be searched from the date of establishment to March 2021 to identify original research articles that report the prevalence of HPV genotypes in Japanese women with normal cervical cytology, low grade, high grade and cancerous cervical lesions. No exclusion criteria relating to language or publication date will be applied. The quality of the studies will be assessed using the Joanna Briggs checklist for prevalence studies. Randomised control trials, cohort studies, cross-sectional and prevalence studies will be considered eligible. Study findings will be combined using a traditional random-effects or fixed-effects meta-analysis to summarise pooled prevalence and 95% confidence intervals depending on heterogeneity. Subgroup analyses and meta-regression will be used to investigate heterogeneity, and sensitivity analyses will be conducted to assess the robustness of the findings., Discussion: To our knowledge, this is the first systematic review protocol that includes both Japanese and English peer-reviewed articles for the determination of genotype-specific HPV prevalence in cytological or histological confirmed normal cervical specimens, low- and high-grade intraepithelial lesions and cervical cancers by age in Japan. We anticipate this information will guide and enhance programme interventions to reduce vaccine-preventable cervical cancer mortality in Japan., Systematic Review Registration: PROSPERO CRD42018117596.

In order to achieve the global elimination of cervical cancer as a public health problem, close surveillance of progress in public health and clinical activities and outcomes across the three pillars of vaccination, screening and treatment will be required. Surveillance should ideally occur within an integrated system that is planned, funded, and regularly evaluated to ensure it is providing timely, accurate and relevant feedback for action. In this paper, we conceptualise the main public health surveillance objectives as process and outcome measures in each of the three pillars. Process measures include coverage/participation measures for vaccination, screening and treatment alongside the ongoing assessment of the quality and reach of these programs and activities. Outcome measures related to the natural history of human papillomavirus (HPV) infection include HPV infection prevalence, precursor cervical lesions and cervical cancers (including stage at diagnosis, cancer incidence and mortality). These outcome measures can be used for monitoring the effectiveness of the three core activities in the short, medium and long term to assess whether these interventions are effectively reducing their occurrence. We discuss possible methods for the surveillance of these measures in the context of country capacity, drawing from examples in Australia, the USA and in low and middle income countries., (Copyright © 2020 Elsevier Inc. All rights reserved.)

To make accurate determinations regarding potential and actual impact of HPV vaccine programs, precise estimates of genotype-specific contributions to disease are required for pre- and post-vaccine populations. Definitive determination of lesion-specific genotypes, particularly where multiple genotypes are detected in a sample, can be technically demanding and resource intensive; therefore, most prevalence studies use mathematical algorithms to adjust for multiple genotype detections. There are currently several algorithms, which can produce genotype estimates within a wide range of variability. The use of these for cervical cytology samples has recently been assessed for accuracy against a definitive reference standard, but none have yet been assessed for multiple-genotype-containing whole biopsy specimens. Using laser capture microdissection (LCM) on biopsy samples, lesion-specific genotype prevalence data were generated for a cohort of 516 young Australian women (aged 18-32 years) with cervical intraepithelial neoplasia grade 3 or adenocarcinoma in situ. Using whole tissue section genotype data from the same cohort, including 71 (13.7%) with multiple genotypes, lesion-associated genotype prevalence was estimated using four different attribution algorithms. The proportion of lesions attributable to HPV16 and HPV18 by LCM were 58.4% and 5%, respectively; hierarchical, proportional, single type/minimum and any type/maximum attribution estimates were comparable across genotypes. For analyses utilising whole tissue biopsy cervical specimens, attribution estimates are appropriate for estimating the proportional contribution of individual genotypes to lesions in a population., 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., (Crown Copyright © 2020. Published by Elsevier Ltd. All rights reserved.)

Background: Autoimmune conditions (AICs) and/or their treatment may alter risk of human papilloma virus (HPV) infection and females with AICs are therefore at an increased risk of cervical dysplasia. However, inclusion of these at-risk populations in cervical cancer screening and HPV-vaccination guidelines, are mostly lacking. This study aimed to determine the prevalence of cervical dysplasia in a wide range of AICs and compare that to HIV and immunocompetent controls to support the optimisation of cervical cancer preventive health measures., Methods: Data linkage was used to match cervical screening episodes to emergency department records of females with AICs or HIV to immunocompetent controls over a 14-year period. The primary outcome was histologically confirmed high-grade cervical disease. Results, measured as rates by cytology and histology classification per 1,000 females screened, were analysed per disease group, and intergroup comparisons were performed., Results: Females with inflammatory bowel disease (2,683), psoriatic and enteropathic arthropathies (1,848), multiple sclerosis (MS) (1,426), rheumatoid arthritis (1,246), systemic lupus erythematosus and/or mixed connective tissue disease (SLE/MCTD) (702), HIV (44), and 985,383 immunocompetent controls were included. SLE/MCTD and HIV groups had greater rates of high-grade histological and cytological abnormalities compared to controls. Increased rates of low-grade cytological abnormalities were detected in all females with AICs, with the exception of the MS group., Conclusions: Females with SLE/MCTD or HIV have increased rates of high-grade cervical abnormalities. The increased low-grade dysplasia rate seen in most females with AICs is consistent with increased HPV infection. These findings support expansion of cervical cancer preventative programs to include these at-risk females., Competing Interests: Dr Foster, Dr Malloy, A/Prof Van Doornum, Dr Unglik and A/Prof Brotherton have no conflict of interest to declare. Dr Jokubaitis has received speaker’s honoraria from Biogen, and conference travel support from Merck. She receives research funding from MS Research Australia, and the Australian National Health and Medical Research Council (NHMRC). Mr. Wrede has received Honoraria and Sponsorship from Biogen and Seqirus. He is Deputy Chairman of the Board of VCS Foundation Pty Ltd. He is a member of the Clinical Expert Panel reviewing the Australian Cervical Screening Program. Prof Butzkueven serves as the Director of the MSBase foundation. He serves on steering committees and advisory boards for Biogen, Roche, Merck, Sanofi, Novartis. He has received speaker’s honoraria, travel support and receives research grant support from Roche, Biogen, Merck, Sanofi, Novartis and Teva. Prof Sasadeusz has been on advisory boards for Merck. Prof Macrae is on advisory committee for Pfizer and receives funding for the conduct of multiple clinical trials in inflammatory bowel disease. He receives funding from Cancer Australia, Cancer Council NSW, and NHMRC for investigator-initiated studies. A/Prof van der Walt has received speaker’s honoraria, travel support and served on advisory boards for Biogen, Merck, Sanofi, Novartis and Teva. She receives funding from the NHMRC Australia. This does not alter our adherence to PLOS ONE policies on sharing data and materials.

Background: Test of Cure (ToC), a combination of testing for oncogenic human papillomavirus (HPV) and cytology, at 12 months post-treatment and annually thereafter, was approved in Australia in 2005 for follow-up of women treated for high-grade squamous intraepithelial lesions (HSIL) of the cervix., Aims: To determine among women resident in Victoria, Australia, the compliance with ToC and the incidence of recurrence up to five years after successful ToC., Materials and Methods: A retrospective analysis of women with HSIL (diagnosed at pre-treatment punch biopsy or at excision) who had excisional treatment between 1 January 2007 and 31 December 2011. De-identified data were retrieved from the Victorian Cervical Cytology Registry in Melbourne as at 24 April, 2015. Successful ToC is defined as the occurrence of two consecutive normal (negative) co-tests. Recurrence after treatment is defined by histologically detected HSIL or greater., Results: There were 8478 women who had excisional treatment for HSIL, with 448 (5.5%) experiencing recurrence. Only 2253 (26.6%) women successfully completed ToC, with a decreasing likelihood of ToC completion by time since year of treatment (32.0% in 2007 compared with 20.9% in 2011). Only one (0.08%) woman had HSIL on histology after successful ToC. From the 2007 cohort, 555 (32.0%) women completed ToC successfully and no HSIL recurrence occurred thereafter (median subsequent follow-up period of 4.7 years)., Conclusions: Our study confirmed that women who successfully complete ToC can be returned to five-year routine screening. However, more concerted efforts are needed to ensure that all women treated complete ToC., (© 2020 The Royal Australian and New Zealand College of Obstetricians and Gynaecologists.)

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.

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., (Copyright © 2018 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

This study demonstrates that the clinical sensitivity, specificity, and reproducibility of the novel cobas human papillomavirus (HPV) test on the cobas 6800 system for high-risk HPV types fulfills the criteria for use in population-based cervical screening. The criteria were formulated by an international consortium, using the cobas 4800 HPV test as a validated reference assay. The cobas HPV test detected over 98% of histologically confirmed cervical intraepithelial neoplasia grade 2+ (CIN2+) lesions in women age 30 years or older, with a specificity of 98.9% compared with the reference cobas 4800 test. Both the intra- and interlaboratory agreement for the cobas HPV test were 98%. The clinical performance of the cobas HPV test is comparable to those of longitudinally validated HPV assays and fulfills the criteria for its use in primary cervical screening., (Copyright © 2019 Saville et al.)