The road to cervical cancer elimination in Malaysia: Evaluation of the impact and cost-effectiveness of human papillomavirus screening with self-collection and digital registry support.

The WHO has launched a global strategy to eliminate cervical cancer through the scale-up of human papillomavirus (HPV) vaccination, cervical screening, and cervical cancer treatment. Malaysia has achieved high-coverage HPV vaccination since 2010, but coverage of the existing cytology-based program remains low. Pilot studies found HPV self-sampling was acceptable and effective, with high follow-up rates when a digital registry was used, and recently the Malaysian Government announced plans for a national HPV-based screening program. We therefore evaluated the impact of primary HPV screening with self-collection in Malaysia in the context of Malaysia's existing vaccination program. We used the "Policy1-Cervix" modeling platform to assess health outcomes, cost-effectiveness, resource use and cervical cancer elimination timing (the year when cervical cancer rates reach four cases per 100 000 women) of implementing primary HPV testing with self-collection, assuming 70% routine-screening coverage could be achieved. Based on available data, we assumed that compliance with follow-up was 90% when a digital registry was used, but that compliance with follow-up would be 50-75% without the use of a digital registry. We found that the current vaccination program would prevent 27 000 to 32 200 cervical cancer cases and 11 700 to 14 000 deaths by 2070. HPV testing with a digital registry was cost-effective (CER = $US 6953-7549 < $US 11 373[<1×GDP per capita]) and could prevent an additional 15 900 to 17 800 cases and 9700 to 10 600 deaths by 2070, expediting national elimination by 11 to 20 years, to 2055 to 2059. If HPV screening were implemented without a digital registry, there would be 1800 to 4900 fewer deaths averted by 2070 and the program would be less cost-effective. These results underline the importance of HPV testing as a key elimination pillar in Malaysia.

Accelerating action on cervical screening in lower- and middle-income countries (LMICs) post COVID-19 era.

Cervical cancer remains the fourth most common cancer in women, with 85% of deaths occurring in LMICs. Despite the existence of effective vaccine and screening tools, efforts to reduce the burden of cervical cancer must be considered in the context of the social structures within the health systems of LMICs. Compounding this existing challenge is the global COVID-19 pandemic, declared in March 2020. While it is too soon to tell how health systems priorities will change as a result of COVID-19 and its impact on the cervical cancer elimination agenda, there are opportunities to strengthen cervical screening by leveraging on several trends. Many LMICs maximized the strengths of their long established community-based primary care and public health systems with expansion of surveillance systems which incorporated mobile technologies. LMICs can harness the momentum of the measures taken against COVID-19 to consolidate the efforts against cervical cancer. Self-sampling, molecular human papillomavirus (HPV) testing and digital health will shift health systems towards stronger public health and primary care networks and away from expensive hospital-based care investments. While COVID-19 will change health systems priorities in LMICs in ways that may de-prioritize cervical cancer screening, there are significant opportunities for integration into longer-term trends towards universal health coverage, self-care and digital health.

Surveillance systems for monitoring cervical cancer elimination efforts: Focus on HPV infection, cervical dysplasia, cervical screening and treatment.

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.

Self-collection cervical screening in the renewed National Cervical Screening Program: a qualitative study.

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.

Uptake and acceptability of human papillomavirus self-sampling in rural and remote aboriginal communities: evaluation of a nurse-led community engagement model.

BACKGROUND: Aboriginal women experience disproportionately higher rates of cervical cancer mortality yet are less likely to participate in screening for early detection. This study sought to determine whether a community-based HPV self-sampling service model can effectively recruit never-screened and under-screened Aboriginal women to participate in cervical cancer screening; assess the clinical outcomes; and explore the acceptability of the model from the perspective of the participants. METHODS: Aboriginal women aged 25-69 years of age were recruited from eight rural and remote communities in New South Wales, Australia to participate in HPV self-sampling via a community-based service model. Outcome measures were: number of women screened by HPV self-sampling, their prior cervical screening status (under-screened or never-screened), clinical outcomes and participation in follow-up pathways of care, and satisfaction with the service model. RESULTS: In total, 215 women conducted a HPV self-sampling test and 200 evaluation surveys were completed. One-fifth of participants (n = 46) were never-screened and one-third (n = 69) were under-screened. Many were unsure of their screening status. Nine women were HPV 16/18 positive and eight had completed all follow up by the conclusion of the study. A further 30 women tested positive for a high risk type other than HPV 16/18 (HPV other), of which 14 had completed follow up at the conclusion of the study. Satisfaction with the HPV self-sampling kit, the process of self-sampling and the service model was high (> 92% satisfied on all items). Many women had difficulty understanding their official HPV results and placed high importance on the nurse explaining it to them. CONCLUSIONS: A community-based service model that respects Aboriginal Women's Business can effectively recruit under-screened and never-screened Aboriginal women to complete cervical cancer screening. Furthermore, this service model supports them to complete recommended follow-up care and engage with their local existing health services.

Compliance with follow-up Test of Cure and outcomes after treatment for high-grade cervical intraepithelial neoplasia in Victoria, Australia.

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.

Management and long-term outcomes of women with adenocarcinoma in situ of the cervix: A retrospective study.

BACKGROUND: Adenocarcinoma in situ of cervix is increasingly managed by local excision rather than hysterectomy and this study will ascertain if conservative management by excision alone is adequate. AIMS: To evaluate the long-term outcomes of conservative management of adenocarcinoma in situ of cervix, particularly in relation to excisional margin status. MATERIALS AND METHODS: Retrospective analysis of women diagnosed with adenocarcinoma in situ and their management between 1992 and 2010 retrieved from the Victorian Cervical Cytology Registry, Australia. Failure of conservative treatment is defined by histologically proven adenocarcinoma in situ or adenocarcinoma at follow-up after negative excisional margins. RESULTS: adenocarcinoma in situ of the cervix was managed primarily with cold knife cone biopsy or loop electrosurgical excision of the cervix. Most excisions were in one piece (83.4%) with average depth of 16.1 mm and 21.9% had involved excisional margins. Women with adenocarcinoma in situ on any excisional margin were more likely to have residual or recurrent disease (28.7%) compared with negative excisional margins (4.3%). Residual adenocarcinoma in situ was twice as common if adenocarcinoma in situ was present at endocervical (29.6%) and stromal (23.1%) margins compared with an ectocervical margin (13.6%). Cancer incidence at follow-up was 2.3% for women with positive excisional margins compared to 1.3% with negative margins. CONCLUSIONS: Women with adenocarcinoma in situ of cervix can be managed with local excisional procedures, best in single pieces to provide the important information on excisional margins. Adenocarcinoma in situ at endocervical and stromal excisional margins needs re-excision or where appropriate, hysterectomy, while negative excisional margins have a low rate of recurrence and can be followed up with test of cure.

Is the positive predictive value of high-grade cytology in predicting high-grade cervical disease falling due to HPV vaccination?

A fall in the positive predictive value (PPV) of cytological predictions of high-grade squamous intra-epithelial lesions (HSIL) or adenocarcinoma-in-situ (AIS) has been predicted in the post-HPV vaccination era due to the decrease in underlying prevalence of cervical lesions. Data was extracted from the Victorian Cervical Screening Registry including cervical cytology tests taken between 2000 and 2016 and any subsequent histology performed within 6 months of the cytology. PPV was calculated for each age group (<20, 20-24, 25-29, 30-34, 35-39, 40-49, 50-59, 60-69, 70+ years) and calendar year. The x2 (chi-square) test was used to identify significant trends in PPV over time in each age group in both the pre-vaccination (2000-2006) and the post-vaccination (2007-2016) periods. The overall PPV of HSIL/AIS cytology in predicting histologically confirmed high grade disease (HGD, HSIL/AIS+) was 75% and this was consistent across the different calendar years. When stratified by age group, there was a decreasing trend in the PPV in women aged <20 years (ptrend = 0.0006) and 20-24 years (ptrend = 0.0004) in the post-vaccination period but not in the pre-vaccination period (ptrend = 0.82 and ptrend = 0.73, respectively). No such decline in PPV was noted in either the pre-vaccination or the post-vaccination periods for any other age groups except the oldest women, aged 60-69 years and 70+ years. The decline in PPV of HSIL/AIS cytology in predicting HGD in age groups <20 and 20-24 years in the post-vaccination period could be an impact of the HPV vaccination.

Clinical Validation of the cobas HPV Test on the cobas 6800 System for the Purpose of Cervical Screening.

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.

Pathways to a cancer-free future: A protocol for modelled evaluations to maximize the future impact of interventions on cervical cancer in Australia.

OBJECTIVE: Australia's HPV vaccination and HPV-based cervical screening programs are changing the landscape in cervical cancer prevention. We aim to identify areas which can make the biggest further impact on cervical cancer burden. This protocol describes the first stage of a program of work called Pathways-Cervix that aims to generate evidence from modelled evaluations of interventions across the cervical cancer spectrum. METHODS: Based on evidence from literature reviews and guidance from a multi-disciplinary Scientific Advisory Committee (SAC), the most relevant evaluations for prevention, diagnosis and treatment were identified. RESULTS: Priority evaluations agreed by the SAC included: increasing/decreasing and retaining vaccination uptake at the current level; vaccinating older women; increasing screening participation; methods for triaging HPV-positive women; improving the diagnosis of cervical intraepithelial neoplasia (CIN) and cancer; treating cervical abnormalities and cancer; and vaccinating women treated for CIN2/3 to prevent recurrence. Evaluations will be performed using a simulation model, Policy1-Cervix previously used to perform policy evaluations in Australia. Exploratory modelling of interventions using idealised scenarios will initially be conducted in single birth cohorts. If these have a significant impact on findings then evaluations with more realistic assumptions will be conducted. Promising strategies will be investigated further by multi-cohort simulations predicting health outcomes, resource use and cost outcomes. CONCLUSIONS: Pathways-Cervix will assess the relative benefits of strategies and treatment options in a systematic and health economic framework, producing a list of 'best buys' for future decision-making in cervical cancer control.

How will transitioning from cytology to HPV testing change the balance between the benefits and harms of cervical cancer screening? Estimates of the impact on cervical cancer, treatment rates and adverse obstetric outcomes in Australia, a high vaccination coverage country.

Primary HPV screening enables earlier diagnosis of cervical lesions compared to cytology, however, its effect on the risk of treatment and adverse obstetric outcomes has not been extensively investigated. We estimated the cumulative lifetime risk (CLR) of cervical cancer and excisional treatment, and change in adverse obstetric outcomes in HPV unvaccinated women and cohorts offered vaccination (>70% coverage in 12-13 years) for the Australian cervical screening program. Two-yearly cytology screening (ages 18-69 years) was compared to 5-yearly primary HPV screening with partial genotyping for HPV16/18 (ages 25-74 years). A dynamic model of HPV transmission, vaccination, cervical screening and treatment for precancerous lesions was coupled with an individual-based simulation of obstetric complications. For cytology screening, the CLR of cervical cancer diagnosis, death and treatment was estimated to be 0.649%, 0.198% and 13.4% without vaccination and 0.182%, 0.056% and 6.8%, in vaccinated women, respectively. For HPV screening, relative reductions of 33% and 22% in cancer risk for unvaccinated and vaccinated women are predicted, respectively, compared to cytology. Without the implementation of vaccination, a 4% increase in treatment risk for HPV versus cytology screening would have been expected, implying a possible increase in pre-term delivery (PTD) and low birth weight (LBW) events of 19 to 35 and 14 to 37, respectively, per 100,000 unvaccinated women. However, in vaccinated women, treatment risk will decrease by 13%, potentially leading to 4 to 41 fewer PTD events and from 2 more to 52 fewer LBW events per 100,000 vaccinated women. In unvaccinated women in cohorts offered vaccination as 12-13 year olds, no change to lifetime treatment risk is expected with HPV screening. In unvaccinated women in cohorts offered vaccination as 12-13 year olds, no change to lifetime treatment risk is expected with HPV screening. HPV screening starting at age 25 in populations with high vaccination coverage, is therefore expected to both improve the benefits (further decrease risk of cervical cancer) and reduce the harms (reduce treatments and possible obstetric complications) associated with cervical cancer screening.

Looking beyond human papillomavirus (HPV) genotype 16 and 18: Defining HPV genotype distribution in cervical cancers in Australia prior to vaccination.

Australia has implemented a high-coverage HPV vaccination program but has not, to date, established the distribution of HPV types that occur in cervical cancers in Australia. This information is important for determining the potential for cervical cancer prevention with both current and broader spectrum HPV vaccines. We analysed 847 cervical cancers diagnosed 2005 to 2015 in tertiary centres in the three most populous Australian states with resolution of specimens containing multiple HPV types using laser-capture microdissection. Archived FFPE tissue was reviewed by specialist pathologists, sandwich sectioned, and initially whole-tissue sections genotyped for HPV. Samples were first genotyped using SPF10-LiPA25 (version 1). Negative samples were screened with DNA ELISA kit HPV SPF10, followed by genotyping with SPF+ LiPA if ELISA positive. If still negative, samples were tested on a qPCR assay targeting the E6 region of HPV16, 18, 45 and 33. Of the 847 cancers (65.1% squamous, 28.7% adenocarcinoma, 4.3% adenosquamous, 2.0% other), 92.9% had HPV detected. Of the HPV-positive cancers, 607 of 787 (77.1%) contained HPV16 or 18, 125 of 787 (15.9%) contained HPV31/33/45/52 or 58, and 55 (7.0%) another HPV type. There was a strong correlation between HPV type and age, with younger women most likely to have HPV16/18 detected and least likely HPV negative. Our findings indicate that cervical cancers diagnosed in Australia more frequently contain HPV16/18 than in international series. This could be due to cervical screening in Australia increasing the proportion of adenocarcinomas, in which types 18 and 16 more strongly predominate, due to prevention of squamous cancers.

Cervical screening with primary HPV testing or cytology in a population of women in which those aged 33 years or younger had previously been offered HPV vaccination: Results of the Compass pilot randomised trial.

BACKGROUND: Using primary human papillomavirus (HPV) testing for cervical screening increases detection of high-grade cervical intraepithelial neoplastic lesions and invasive cancer (cervical intraepithelial neoplasia grade 2+ [CIN2+]) compared to cytology, but no evaluation has been conducted in a population previously offered HPV vaccination. We aimed to assess colposcopy referral and CIN2+ detection rates for HPV-screened versus cytology-screened women in Australia's HPV-vaccinated population (by 2014, resident women ≤33 years had been age-eligible for HPV vaccination, with 3-dose uptake across age cohorts being about 50%-77%). METHODS AND FINDINGS: Compass is an open-label randomised trial of 5-yearly HPV screening versus 2.5-yearly liquid-based cytology (LBC) screening. In the first phase, consenting women aged 25-64 years presenting for routine screening at 47 primary practices in Victoria, Australia, provided a cervical sample and were randomised at a central laboratory at a 1:2:2 allocation to (i) image-read LBC screening with HPV triage of low-grade cytology ('LBC screening'), (ii) HPV screening with those HPV16/18 positive referred to colposcopy and with LBC triage for other oncogenic (OHR) types ('HPV+LBC triage'), or (iii) HPV screening with those HPV16/18 positive referred to colposcopy and with dual-stained cytology triage for OHR types ('HPV+DS triage'). A total of 5,006 eligible women were recruited from 29 October 2013 to 7 November 2014 (recruitment rate 58%); of these, 22% were in the group age-eligible for vaccination. Data on 4,995 participants were analysed after 11 withdrawals; 998 were assigned to, and 995 analysed (99.7%) in, the LBC-screened group; 1,996 assigned to and 1,992 analysed (99.8%) in the HPV+LBC triage group; and 2,012 assigned to and 2,008 analysed (99.8%) in the HPV+DS triage group. No serious trial-related adverse events were reported. The main outcomes were colposcopy referral and detected CIN2+ rates at baseline screening, assessed on an intention-to-treat basis after follow-up of the subgroup of triage-negative women in each arm referred to 12 months of surveillance, and after a further 6 months of follow-up for histological outcomes (dataset closed 31 August 2016). Analysis was adjusted for whether women had been age-eligible for HPV vaccination or not. For the LBC-screened group, the overall referral and detected CIN2+ rates were 27/995 (2.7% [95% CI 1.8%-3.9%]) and 1/995 (0.1% [95% CI 0.0%-0.6%]), respectively; for HPV+LBC triage, these were 75/1,992 (3.8% [95% CI 3.0%-4.7%]) and 20/1,992 (1.0% [95% CI 0.6%-1.5%]); and for HPV+DS triage, these were 79/2,008 (3.9% [95% CI 3.1%-4.9%]) and 24/2,008 (1.2% [95% CI 0.8%-1.6%]) (p = 0.09 for difference in referral rate in LBC versus all HPV-screened women; p = 0.003 for difference in CIN2+ detection rate in LBC versus all HPV-screened women, with p = 0.62 between HPV screening groups). Limitations include that the study population involved a relatively low risk group in a previously well-screened and treated population, that individual women's vaccination status was unknown, and that long-term follow-up data on disease detection in screen-negative women are not yet available. CONCLUSIONS: In this study, primary HPV screening was associated with significantly increased detection of high-grade precancerous cervical lesions compared to cytology, in a population where high vaccine uptake was reported in women aged 33 years or younger who were offered vaccination. It had been predicted that increased disease detection might be associated with a transient increase in colposcopy referral rates in the first round of HPV screening, possibly dampened by HPV vaccine effect; in this study, although the point estimates for referral rates in women in each HPV-screened group were 41%-44% higher than in cytology-screened women, the difference in referral rate between cytology- and HPV-screened women was not significant. These findings provide initial support for the implementation of primary HPV screening in vaccinated populations. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry ACTRN12613001207707.

Biological and Behavioral Factors Associated With Positive Chlamydia Retests.

BACKGROUND: Repeat chlamydia detection after treatment is common, and there is concern that treatment failure may be a cause. METHODS: Within a randomized trial, we established a prospective cohort of 600 participants with anogenital chlamydia diagnoses (200 each of women, heterosexual men, and men who have sex with men [MSM]). Participants were invited for repeat testing at 3 months and to complete a behavioral survey at 4 months. Positive samples were analyzed for organism DNA load and genovar. We estimated repeat chlamydia positivity, reinfection and treatment failure rates, and investigated the biological and behavioral factors associated with a repeat positive test. RESULTS: A total of 290 participants (100 women, 89 heterosexual men, 101 MSM) were retested at 1 to 4 months, with 43 repeat positives, including 26 classed as reinfection and 9 as treatment failures. Comparing MSM with heterosexual men and women combined, repeat positivity was higher (20.8% vs 11.6%, P = 0.04), and treatment failure was higher (6.9% vs 1.1%, P = 0.01), but there was no difference in reinfection rates (11.9% vs 7.4%, P = 0.21). Among MSM, the odds of repeat positivity increased by 90% with each additional log organism load in the original specimen (baseline) (adjusted odds ratio, 1.9; 95% confidence interval, 1.1-3.2). Among heterosexuals, the odds of repeat positivity decreased by 10% with each additional week delay in being retested for chlamydia (adjusted odds ratio, 0.9; 95% confidence interval, 0.8-0.9). CONCLUSIONS: Positive retests were more common among MSM than heterosexuals. Treatment failure was more common in MSM with rectal chlamydia, reinforcing concerns about azithromycin treatment failure.

Home-based HPV self-sampling improves participation by never-screened and under-screened women: Results from a large randomized trial (iPap) in Australia.

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.

Transitioning from cytology-based screening to HPV-based screening at longer intervals: implications for resource use.

BACKGROUND: Following a recent major review of cervical screening, from 2017 Australia will transition from two-yearly cytology-based screening to five-yearly primary HPV screening, with partial genotyping and direct referral for HPV 16/18 and LBC triage for other oncogenic types. Switching to a longer screening interval will result in transitional fluctuations for volumes of tests before a 'steady state' is reached for the new test volumes. This study aimed to quantify the impact of this transition on year-to-year volumes of screening and follow-up tests and procedures. METHODS: Number of women screened and test volumes from 2015 to 2032 were estimated via a detailed simulation model which explicitly modelled varying screening and HPV vaccination exposure in individual birth cohorts, and fully incorporated how a relatively rapid screening program switch in 2017 would affect both women attending for routine screening and those in surveillance following an abnormality. RESULTS: Numbers of women screened and HPV tests are predicted to fluctuate in the first screening rounds as a result of the transition to a longer screening interval (mean women screened and HPV tests 1.4 million in the first 5-year period, year-to-year fluctuation > +/-50%; mean 1.5 million women/HPV tests in third 5-year period, fluctuation approximately +/-25%). The extent to which this fluctuation was predicted to carry through to secondary tests/procedures was less (fluctuations of +25%/-31% in first 5-year period; decreasing to +8%/-10% by third round). HPV vaccination is predicted to counteract increases in high grade cytology results, colposcopies and precancer treatments which would otherwise occur due to population increases. Precancer treatments are predicted to drop below 2015 levels within the first few years of program switchover. Mean colposcopy volumes are predicted to be similar to 2015 levels by the third round of HPV-based screening, and also be 25-40% lower than would have occurred in the absence of HPV vaccination. CONCLUSIONS: While numbers of women attending for screening and HPV tests are anticipated to initially fluctuate as a result of the transition to a longer recommended interval, there is expected to be less fluctuation in follow-up tests and procedures; however these will still have a significant impact on operational aspects of the screening program. Detailed modelling of the switchover process gave important insights into how volumes would be affected.

Women's experience with home-based self-sampling for human papillomavirus testing.

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.