National experience in the first two years of primary human papillomavirus (HPV) cervical screening in an HPV vaccinated population in Australia: observational study.

OBJECTIVE: To review the first two years of the primary human papillomavirus (HPV) cervical screening programme in an HPV vaccinated population. DESIGN: Observational study. SETTING: Australia. PARTICIPANTS: 3 745 318 women with a primary HPV test between 1 December 2017 and 31 December 2019; most women aged <40 years had previously been offered vaccination against HPV16 and HPV18. INTERVENTIONS: Primary HPV screening with referral if HPV16 or HPV18 (HPV16/18) positive and triage with liquid based cytology testing (threshold atypical squamous cells-cannot exclude high grade squamous intraepithelial lesion) for women who were positive for high risk HPV types other than 16/18. A 12 month follow-up HPV test was recommended in triaged women with a negative or low grade cytology result, with referral if they tested positive for any high risk HPV type at follow-up. MAIN OUTCOME MEASURES: Proportion of women who had attended for their first HPV screening test, tested positive, and were referred for colposcopy; and short term risk of detecting cervical intraepithelial neoplasia (CIN) grade 2 or worse, CIN grade 3 or worse, or cancer. RESULTS: 54.6% (n=3 507 281) of an estimated 6 428 677 eligible women aged 25-69 had undergone their first HPV test by the end of 2019. Among those attending for routine screening, positivity for HPV16/18 and for HPV types not 16/18 was, respectively, 2.0% and 6.6% in women aged 25-69 (n=3 045 844) and 2.2% and 13.3% in highly vaccinated cohorts of women aged 25-34 (n=768 362). Colposcopy referral (ages 25-69 years) was 3.5%, increasing to an estimated 6.2% after accounting for women who had not yet had a 12 month repeat test. Cervical cancer was detected in 0.98% (456/46 330) of women positive for HPV16/18 at baseline, including 0.32% (89/28 003) of women with HPV16/18 and negative cytology. Women with HPV types not 16/18 and negative or low grade cytology at both baseline and 12 months were at low risk of serious disease (3.4% CIN grade 3 or worse; 0.02% cancer; n=20 019) but estimated to account for 62.0% of referrals for this screening algorithm. CONCLUSIONS: Colposcopy referral thresholds need to consider underlying cancer risk; on this basis, women with HPV16/18 in the first round of HPV screening were found to be at higher risk regardless of cytology result, even in a previously well screened population. Women with HPV types not 16/18 and negative or low grade cytology showed a low risk of serious abnormalities but constitute most referrals and could be managed safely with two rounds of repeat HPV testing rather than one. HPV16/18 driven referrals were low in HPV vaccinated cohorts.

HPV self-sampling and follow-up over two rounds of cervical screening in Australia - the iPap trial.

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.

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.

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.

Time to clinical investigation for Indigenous and non-Indigenous Queensland women after a high grade abnormal Pap smear, 2000-2009.

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.

Genetic and Environmental Factors in Invasive Cervical Cancer: Design and Methods of a Classical Twin Study.

BACKGROUND: Persistent high-risk human papillomavirus (HPV) infection is a necessary prerequisite for development of cervical cancer and its precursor lesion, high-grade squamous intraepithelial lesion (HSIL). However, HPV infection is not sufficient to drive this process, and genetic and environmental factors may also play a role. METHODS/DESIGN: The Cervical Cancer, Genetics and Environment Twin Study was established to investigate the environmental and genetic influences on variation in susceptibility to cervical pre-cancer in 25- to 69-year-old monozygotic (MZ) and dizygotic (DZ) twins recruited through the Australian Twin Registry. Reviews of Papanicolaou (Pap) screening histories were undertaken to identify individual women with a history of an abnormal Pap test. This was followed by detection of HPV in archival Pap smears of selected twin pairs to determine HPV persistence. Selected twin pairs also completed a detailed questionnaire on socio-demographic characteristics, sexual behavior, and HPV knowledge. In future analyses, under the assumptions of the classical twin design, case-wise concordance for persistent HPV infection and HSIL will be calculated for MZ and DZ twin pairs, and twin pairs (both MZ and DZ) who are discordant for the above outcomes will be used to assess the contributions of measured environmental risk factors. DISCUSSION: The study examines factors related to HPV persistence and development of HSIL among female MZ and DZ twins. The results will contribute to our understanding of the natural history of cervical HPV infection and the relative contributions of genetic and environmental factors in disease progression.

The first comprehensive report on Indigenous Australian women's inequalities in cervical screening: A retrospective registry cohort study in Queensland, Australia (2000-2011).

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.

Cervical Abnormalities Are More Common among Indigenous than Other Australian Women: A Retrospective Record-Linkage Study, 2000-2011.

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.

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.

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.

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.

A pilot study to compare dry cervical sample collection with standard practice of wet cervical samples for human papillomavirus testing.

BACKGROUND: For human papillomavirus (HPV) DNA detection, specimen collection and transportation using a dry swab without transport medium has advantages, in various situations, over liquid media. OBJECTIVE: In this pilot study we evaluated whether a dry cervical sample taken with a flocked swab (dry sample) is a valid alternative for HPV DNA testing compared with the standard practice of a wet sample taken with a cyto-broom placed directly into liquid media (wet sample). STUDY DESIGN: Women attending the dysplasia clinic at the Royal Women's Hospital, Melbourne Australia between November 2013 and February 2014 were enrolled. During colposcopic examination, a practitioner collected wet and dry cervical samples, with the order of collection randomised. In the laboratory both samples were left for a week before being tested for 14 high-risk HPV types using the Roche Cobas 4800 test. RESULTS: Overall, 209 had valid HPV results from both samples. The observed agreement for HPV detection between wet and dry samples was 92.8% and kappa was 0.85 (95% confidence interval (95% CI): 0.78-0.92). There was no statistical difference in the percent HPV positive for each sample (p = 0.30). HPV testing of the dry sample had an 88.5% (95% CI: 79.9-94.3%) sensitivity for HPV detected using the wet specimen. For the HPV results categorized hierarchically, there was 92.8% overall agreement and a kappa of 0.87 (95% CI = 0.80-0.93) for the paired results. CONCLUSION: Using dry flocked swabs to collect cervical cells is a valid alternative to collecting wet samples for HPV DNA testing using a PCR based test.

Women's views on human papillomavirus self-sampling: focus groups to assess acceptability, invitation letters and a test kit in the Australian setting.

UNLABELLED: Background The study evaluated acceptability, invitation letters and the test kit for a trial of human papillomavirus (HPV) self-sampling among never- and under-screened women in Australia. METHODS: Victorian women, 30-69 years, who had never had a Pap test or were overdue for one, participated. Four focus groups including eight to nine participants segmented by age (30-49 and 50-69 years) and screening history (never- and under-screened) were conducted in August 2013. Discussions were recorded and transcribed verbatim and data analysed using thematic content analysis. RESULTS: The response to the concept of HPV self-sampling was positive. Decision-making was largely influenced by the content of a pre-invitation letter. Appealing features of self-sampling were cost (free), convenience (home-based) and anticipated less discomfort (with a swab) than a Pap test. Small kits that fit in mailboxes were preferred over post office parcel collection. The perceived barriers include concerns about test accuracy and lack of confidence that a home-based test would give the same results as a physician administered test. Women wanted information on the timing of receipt of the results and information about the organisation providing the test. CONCLUSION: HPV self-sampling is a possible alternative for Australian women who are reluctant to have a Pap test and may increase the likelihood of participation in cervical cancer screening if women's concerns about it can be addressed. The findings of this study are relevant for researchers, policymakers and practitioners implementing self-sampling for under-screened women as part of cervical screening programs.

Assessing genital human papillomavirus genoprevalence in young Australian women following the introduction of a national vaccination program.

OBJECTIVES: Following the implementation of Australia's National HPV Vaccination Program in April 2007, this study evaluated the prevalence of vaccine-targeted human papillomavirus (HPV) genotypes (HPV 6, 11, 16, 18) amongst vaccine-eligible young women. METHODS: Between September 2011 and August 2013, women from Victoria, Australia aged 18-25 were recruited through targeted advertising on the social networking website Facebook. Participants completed an online questionnaire, and sexually active women were asked to provide a self-collected vaginal swab for HPV deoxyribonucleic acid (DNA) detection and genotyping. Samples positive for HPV were genotyped using the Linear Array HPV genotyping test (Roche Diagnostics). Self-reported HPV vaccination details were verified with the National HPV Vaccination Program Register (NHVPR). RESULTS: Of 431 vaginal swabs, 24.8% were positive for HPV DNA. Vaccine-targeted HPV genotypes were detected in only seven (1.6%) samples; all HPV 16 (of the six HPV 16 positive vaccinated women, all had received the vaccine after sexual debut). There were no cases of HPV 6, 11 or 18 identified. HPV types 51, 59, 73, 84, and 89 were the most prevalent genotypes. Vaccination rates were high, with 77.3% of participants having received all three doses of the vaccine, and there was an 89.8% concordance between self-reported and registry-reported HPV vaccination status. Strong associations were observed between vaccination status, age, language spoken at home and country of birth, as well as between HPV detection and the number of male sexual partners. CONCLUSION: Preliminary data from this study demonstrate a very low prevalence of vaccine-related HPV genotypes amongst vaccine-eligible women from Victoria, Australia. We were able to use Facebook to effectively reach and recruit young women to participate in the assessment of the impact of Australia's HPV vaccination program.

Cervical screening rates for women vaccinated against human papillomavirus.

OBJECTIVE: To compare cervical screening rates for women vaccinated with a quadrivalent human papillomavirus (HPV) vaccine with those for unvaccinated women, to address concerns that vaccinated women may not be participating in cervical screening. DESIGN, SETTING AND PARTICIPANTS: Cross-sectional analysis of linked data from the Victorian Cervical Cytology Registry and the National HPV Vaccination Program Register for 20-29-year-old women in Victoria, Australia, for the period 1 January 2009 to 31 December 2011. MAIN OUTCOME MEASURES: Screening participation rates for vaccinated and unvaccinated women. RESULTS: Participation in cervical screening during the 2-year period 2010-2011 was significantly lower in 20-24-year-old vaccinated women compared with unvaccinated women of the same age (37.6% v 47.7%, a 10.1 percentage point difference [95% CI, 9.7-10.6]; P < 0.001) and significantly lower in 25-29-year-old vaccinated women compared with unvaccinated women of the same age (45.2% v 58.7%, a 13.5 percentage point difference [95% CI, 13.1%-13.9%]; P < 0.001). Similar results were observed for participation during the 3-year period 2009-2011. CONCLUSIONS: Despite education messages provided to young women, our results suggest that vaccinated women are being screened at lower rates than unvaccinated women in Australia. While some degree of undermatching of women in the study may have occurred, this cannot wholly explain our findings. Effective implementation of Individual Healthcare Identifiers to health records, including registry records, is needed to prevent potential undermatching of individuals in future linkage studies. In the meantime, efforts to increase participation in cervical screening by vaccinated women are needed.

Rationale and design of the iPap trial: a randomized controlled trial of home-based HPV self-sampling for improving participation in cervical screening by never- and under-screened women in Australia.

BACKGROUND: Organized screening based on Pap tests has substantially reduced deaths from cervical cancer in many countries, including Australia. However, the impact of the program depends upon the degree to which women participate. A new method of screening, testing for human papillomavirus (HPV) DNA to detect the virus that causes cervical cancer, has recently become available. Because women can collect their own samples for this test at home, it has the potential to overcome some of the barriers to Pap tests. The iPap trial will evaluate whether mailing an HPV self-sampling kit increases participation by never- and under-screened women within a cervical screening program. METHODS/DESIGN: The iPap trial is a parallel randomized controlled, open label, trial. Participants will be Victorian women age 30-69 years, for whom there is either no record on the Victorian Cervical Cytology Registry (VCCR) of a Pap test (never-screened) or the last recorded Pap test was between five to fifteen years ago (under-screened). Enrolment information from the Victorian Electoral Commission will be linked to the VCCR to determine the never-screened women. Variables that will be used for record linkage include full name, address and date of birth. Never- and under-screened women will be randomly allocated to either receive an invitation letter with an HPV self-sampling kit or a reminder letter to attend for a Pap test, which is standard practice for women overdue for a test in Victoria. All resources have been focus group tested. The primary outcome will be the proportion of women who participate, by returning an HPV self-sampling kit for women in the self-sampling arm, and notification of a Pap test result to the Registry for women in the Pap test arm at 3 and 6 months after mailout. The most important secondary outcome is the proportion of test-positive women who undergo further investigations at 6 and 12 months after mailout of results. DISCUSSION: The iPap trial will provide strong evidence about whether HPV self-sampling could be used in Australia to improve participation in cervical screening for never-and under-screened women. TRIAL REGISTRATION: ANZCTR Identifier: ACTRN12613001104741; UTN: U1111-1148-3885.

High-grade cervical abnormalities and cervical cancer in women following a negative Pap smear with and without an endocervical component: a cohort study with 10 years of follow-up.

The proportion of Pap smears containing an endocervical component (ECC) has been declining in Australia. Given that ECC negative (ECC-) smears may be associated with reduced sensitivity, we undertook a retrospective cohort study to estimate rates of histologically confirmed high-grade cervical abnormality (HGA) and cancer in women with negative Pap smears with and without an ECC. Women 18-69 years with at least two Pap smears between 1 January 2001 and 31 December 2010 with the first smear in that period (index smear) showing no abnormality were eligible. Follow-up ended at date of the first abnormal smear, date of histological diagnosis, date of hysterectomy, date of death, or 31 December 2010, whichever came first. ECC status was treated as a time varying exposure. Follow-up was split at each smear after the index smear. Poisson regression was used to estimate adjusted incidence rates and incidence rate ratios (IRR) by ECC status. The incidence rate of histologically confirmed HGA was significantly lower following ECC- smears than after ECC+ smears (adjusted IRR: 0.69, 95%Confidence Interval (CI) 0.62-0.77), particularly at older ages (interaction between ECC status and age, p = 0.001). In contrast, the overall rate of invasive cancer was not significantly different after ECC- than after ECC+ smears (IRR: 1.27, 95%CI 0.90-1.77). In conclusion, women had a lower rate of confirmed HGA and no significant increase in the rate of invasive cervical cancer following ECC- smears. This study does not support differential (accelerated) follow-up in women with a negative smear without an endocervical component.