Julia M. L. Brotherton

Global status of HPV vaccination two decades in: effective, safe and preventing cancer

Prophylactic human papillomavirus vaccines have been in use in populations worldwide for nearly 20 years. Much has been learnt in relation to their effectiveness, safety, and how best to effectively implement them in populations to prevent cancer and other HPV-related diseases. Global challenges such as limited supply and the mismatch between those who can afford them and those with the greatest disease burden from cervical cancer have prevented optimal usage to date. Here we identified recent papers and focus upon the accumulated evidence regarding HPV vaccine: i) effectiveness in preventing cancer and precancerous lesions, ii) safety in population usage, iii) trial evidence supporting registration of four newer vaccines, iv) progress in country-level introductions and coverage, and v) lessons learned in effective implementation. Reasons for optimism are many, with vast cumulative knowledge on impact, safety and implementation and accelerating HPV vaccine introductions, simplification of delivery and reduced costs through single dose approaches and supply constraints easing. However, considerable challenges remain in achieving and maintaining high and equitable global coverage, given the uncertainty in funding, risk to ongoing prioritization of health equity and to vaccine confidence in the current global public health environment.

‘ Why Didn't I Get That Choice?’ : A Qualitative Exploration of How Cervical Screening Choices Are Understood and Experienced by Screen‐Eligible People in Australia, Two Years After Self‐Collection Became an Option for All

ABSTRACT Background Australia's human papillomavirus (HPV)‐based National Cervical Screening Program guidelines state that anyone eligible for screening should be offered a choice of using self‐collection or clinician collection for initial screening. Aim To explore the awareness and experiences of women and people with a cervix who have been screened since this choice became available in July 2022. Methods Semi‐structured online or telephone interviews were conducted between February and May 2024 with 43 Victorian women and people with a cervix, aged 25–74 years. All participants self‐reported completing a cervical screen within 12 months of our study. Interview data were recorded, transcribed verbatim and thematically analysed before being mapped to The Ottawa Decision Support Framework. Self‐reported screening history was confirmed with de‐identified data from the National Cancer Screening Register (NCSR) Victorian Raw Data Extract (November 2024). Results Fewer than half (19, 44%) of those interviewed were given a choice at their most recent screen, with variation in how options were presented by healthcare providers. Participants felt they lacked awareness and knowledge to feel confident in their options. Most participants viewed having a choice as important and, even if they did not prefer self‐collection for themselves, noted benefits for others. Some felt disappointed or angry about not having a choice, while others were happy to defer to their doctor. Relationships with, and the views of, healthcare providers strongly influenced decision‐making. Participants reflected on potential advantages of self‐collection if it could reduce the cost of appointments and be accessed in more flexible ways. Among the 38 participants who consented to screening history verification, the self‐reported data showed reasonable accuracy (67%) against the NCSR. Conclusion Despite a clear policy directive for practitioners to offer a choice to all eligible individuals, many recent screeners were not offered the choice or lacked the knowledge, confidence and decision supports needed to make an informed choice. The choice of screening method appears strongly influenced by if, and how, options are presented by healthcare providers. A range of strategies are needed to ensure screeners feel empowered, supported and informed to make and carry out a real choice. Patient or Public Contribution Members of the public were involved in interviews. Findings were summarised and disseminated via a short report. A consumer advisory panel provided feedback on the content, readability and length of all patient‐facing resources.

Stakeholder perspectives on HPV vaccination uptake among Aboriginal and Torres Strait Islander adolescents via the school immunisation programmes in Queensland: a qualitative study

Introduction Aboriginal and Torres Strait Islander women experience inequitable cervical cancer outcomes including higher incidence and mortality rates than other Australian women. Cervical cancer can be prevented through human papillomavirus (HPV) vaccination, which is primarily delivered through school immunisation programmes and found to be very effective. However, Aboriginal and Torres Strait Islander adolescents have lower rates of HPV vaccination uptake compared with non-Indigenous adolescents. Objectives This study explored the perspectives and experiences of HPV vaccination programme providers and school staff involved in the delivery of school-based HPV vaccination programmes for Aboriginal and Torres Strait Islander adolescents in Queensland. Design This qualitative project recruited 10 maximally diverse schools to participate. We purposively invited immunisation programme providers and school staff associated with delivering or supporting and used a snowballing approach to recruitment. We used an Indigenist Research approach and an ecological model for health to centre Aboriginal and Torres Strait Islander experiences and priorities. Participants We interviewed 18 immunisation programme providers and school staff involved in delivery between 2020 and 2022. Interview topics included programme delivery and processes, engagement with Aboriginal and Torres Strait Islander adolescents and caregivers, factors impacting uptake and completion, and suggestions for improvement. Results Stakeholders highlighted multilayered challenges navigating a school-based immunisation programme across health and education sectors, especially within the context of the COVID-19 pandemic. This included logistical barriers around programme coordination and scheduling, roles and responsibilities, and communication issues between schools, programme providers, caregivers and adolescents. Four themes were identified: (1) co-ordination of the clinic between schools and programme providers, (2) supporting Aboriginal and Torres Strait Islander families through the vaccination pathway, (3) HPV vaccination resources and (4) COVID-19 disruptions to HPV vaccination programme. Conclusions The findings suggest a need for better communication and coordination of the school-based clinic, including consideration of staff capacity and school resources; enhanced linkages with and support for Aboriginal and Torres Strait Islander student support staff and community organisations who play a critical role in supporting adolescents’ vaccination, and flexible methods of consent supported by culturally appropriate resources. These findings informed recommendations for improved practice and will contribute towards reaching Australia’s cervical cancer elimination targets.

The acceptability of, and informational needs related to, self‐collection cervical screening among women of Indian descent living in Victoria, Australia: A qualitative study

AbstractBackgroundIn July 2022, self‐collection became universally available as part of Australia's National Cervical Screening Program. This change aims to address screening inequities experienced among underscreened populations, including women of Indian descent. This study explored experiences of cervical screening, alongside the acceptability of self‐collection, among women of Indian descent living in Victoria, Australia. We also aimed to articulate the informational needs to promote self‐collection among this population.MethodsFive focus group discussions with 39 women living in Victoria were conducted in English (n = 3) and Punjabi (n = 2). Transcripts were thematically analysed, as informed by the Theoretical Framework of Acceptability.ResultsWomen were motivated by the choice to self‐collect, perceiving the ability to maintain modesty and greater autonomy as key enablers. Healthcare practitioners were seen as central in supporting patient‐centred models of care. Perceived barriers to self‐collection included concerns around its accuracy and women's confidence in collecting their own sample. Widespread dissemination of culturally tailored promotion strategies communicating concepts such as 'privacy' and 'accuracy' were suggested by women to promote self‐collection.ConclusionSelf‐collection was highly acceptable among women of Indian descent, particularly when assured of its accuracy, and sociocultural norms and previous screening experiences are considered. This study highlights the huge potential that self‐collection can play in increasing equity in Australia's cervical screening programme.Patient or Public ContributionMembers of the public were involved in focus group discussions. Findings were summarised and disseminated via a poster. A bicultural worker was involved in all stages of the research.

What young women (aged 24–29 years) in Australia think about self-collection for cervical screening: a brief report

Background In mid-2022 Australia’s National Cervical Screening Program made self-collection of a vaginal sample an option for screening for young women or people with a cervix aged 25 to 29 years for the first time. This study explored what young women thought about, and wanted to know about, self-collection, and what their future screening preferences are. Methods Young women (n = 21), aged 24–29 years, were recruited through social media. Semi-structured interviews explored screening history, screening preferences and thoughts about self-collection. Data were analysed using an a priori coding framework informed by the Theoretical Framework of Acceptability. Results Young women valued the addition of self-collection to the national cervical screening program, believing it to be less invasive and more convenient. However, they also valued the choice to opt for a clinician-collected specimen if preferred. Conclusions Self-collection is a valuable addition to the National Cervical Screening Program. This study suggests that continued efforts are needed to raise awareness of its availability, and improve understanding about its accuracy, the ease of collection, that you still need to engage with a primary healthcare service to access it and that you can still opt for a clinician-collected test.

Could HPV Testing on Self-collected Samples Be Routinely Used in an Organized Cervical Screening Program? A Modeled Analysis

Abstract Background: Cervical screening on self-collected samples has mainly been considered for targeted use in underscreened women. Updated evidence supports equivalent sensitivity of PCR-based human papillomavirus (HPV) testing on self-collected and clinician-collected samples. Methods: Using a well-established model, we compared the lifetime impact on cancer diagnoses and deaths resulting from cervical screening using self-collected samples only, with and without the existing restriction in Australia to women aged 30+ years and ≥2 years overdue, compared with the mainstream program of 5-yearly HPV screening on clinician-collected samples starting at 25 years of age. We conservatively assumed sensitivity of HPV testing on self-collected relative to clinician-collected samples was 0.98. Outcomes were estimated either in the context of HPV vaccination (“routinely vaccinated cohorts;” uptake as in Australia) or in the absence of HPV vaccination (“unvaccinated cohorts”). Results: In unvaccinated cohorts, the health benefits of increased participation from self-collection outweighed the worst case (2%) loss of relative test sensitivity even if only 15% of women, who would not otherwise attend, used it (“additional uptake”). In routinely vaccinated cohorts, population-wide self-collection could be marginally (0.2%–1.0%) less effective at 15% additional uptake but 6.2% to 12.4% more effective at 50% additional uptake. Most (56.6%–65.0%) of the loss in effectiveness in the restricted self-collection pathway in Australia results from the requirement to be 2 or more years overdue. Conclusions: Even under pessimistic assumptions, any potential loss in test sensitivity from self-collection is likely outweighed by improved program effectiveness resulting from feasible levels of increased uptake. Impact: Consideration could be given to offering self-collection more widely, potentially as an equal choice for women. See related commentary by Lim, p. 245

Implementation of Australia’s renewed cervical screening program: Preparedness of general practitioners and nurses

The National Cervical Screening Program (NCSP) in Australia underwent major changes on December 1st, 2017. The program changed from 2-yearly Pap testing for women aged 18-69 years to 5-yearly HPV testing for women aged 25-74 years including differential management pathways for oncogenic HPV 16/18 positive versus HPV non16/18 positive test results and the option of self-collection for under-screened women. We conducted a survey among cervical screening providers in primary care to assess their level of preparedness in undertaking cervical screening before (pre-renewal) and after (post-renewal) the new program was implemented. Surveys were conducted between 14th August and 30th November 2017 (pre-renewal) and 9th February and 26th October 2018 (post-renewal) among cervical screening providers who attended education sessions related to the new guidelines. Preparedness was assessed in three areas: 1) level of comfort implementing the new guidelines (7 questions), 2) level of confidence in their ability to convey information about the new guidelines (9 questions) and 3) level of agreement regarding access to resources to support implementation (11 questions). Proportions were calculated for each question response and pre- and post-renewal periods compared using generalised linear models. Open-ended questions related to anticipated barriers and ways to overcome barriers were also included in the questionnaires. Compared to the pre-renewal period, a higher proportion of practitioners in the post-renewal period were more comfortable offering routine screening to women ≥25 years (p = 0.005) and more confident explaining the rationale for not screening before 25 years (p = 0.015); confident explaining a positive HPV 16/18 (p = 0.04) and HPV non 16/18(p = 0.013) test result and were comfortable with not referring women with a positive HPV non 16/18 test result and low grade/negative cytology for colposcopy (p = 0.01). A higher proportion of Victorian practitioners in the post-renewal period sample were also comfortable (p = 0.04) and confident (p = 0.015) recommending self-collection to under-screened women and agreed that self-collection is a reliable test (p = 0.003). The most commonly reported suggestion was to provide information, education and communication materials to both patients and practitioners. Compared to the pre-renewal period, practitioners in the post-renewal period were better prepared to implement the renewed screening program. Healthcare providers require further support to implement the self-collection pathway.

Under-screened Aboriginal and Torres Strait Islander women’s perspectives on cervical screening

Aboriginal and Torres Strait Islander women have lower participation in Australia’s National Cervical Screening Program than other Australian women. Under-screened (including never screened) women’s voices are rarely heard in research evidence, despite being a priority group for interventions to increase cervical screening participation. This study aimed to describe under-screened Aboriginal and Torres Strait Islander women’s perspectives on cervical screening. Participants were 29 under-screened (women who had either never screened, had not screened in the previous five years or had recently screened in the past three months after more than five years) Aboriginal and Torres Strait Islander women from five communities across three states/territories. Female Aboriginal and Torres Strait Islander researchers Yarned with women about why they did not participate in screening and how to improve screening. Yarning is an Indigenous qualitative research method in which relationships and trust facilitate culturally safe conversation. Transcripts were analysed thematically. The proportion of eligible women who screened within 30 days after the Yarn was calculated. We identified four themes describing how the harms outweighed the benefits of cervical screening for under-screened women. These were: 1) distress, discomfort, and trauma; 2) lack of privacy and control; 3) complicated relationships with health care providers (HCPs); and 4) pressured, insensitive, and/or culturally unsafe communication from HCPs. Under-screened women who had recently screened had maintained privacy and control through self-collection and had experienced trauma-informed and empathetic care from their HCPs. While we cannot unequivocally attribute women’s subsequent participation in screening to their involvement in this study, it is notable that one third of eligible under-screened women were screened within 30 days after the Yarn. Enhancing privacy, implementing trauma-informed approaches to care and sensitivity to the clinician-client relationship dynamics could enhance women’s sense of comfort in, and control over, the screening procedure. The opportunity to Yarn about cervical screening and self-collection may address these issues and support progress toward cervical cancer elimination in Australia.

Psychosocial impact of testing human papillomavirus positive in Australia's human papillomavirus‐based cervical screening program: A cross‐sectional survey

AbstractObjectiveTo examine the impact of self‐reported human papillomavirus (HPV) test result (HPV negative, HPV positive, HPV result unknown) on a range of psychosocial outcomes.MethodsWomen and other people with a cervix in Australia aged 25–74 years who reported having participated in cervical screening since December 2017 were recruited through Facebook and Instagram to complete an online survey. The primary outcome measures were anxiety, emotional distress, and general distress.ResultsNine hundred fifteen participants completed the online survey; 73.2% reported testing HPV negative (‘HPV−’), 15% reported testing HPV positive (‘HPV+’) and 11.8% reported that they did not know/remember their test result (‘HPV unknown’). Compared to participants testing HPV−, participants testing HPV+ had higher mean anxiety (41.67 vs. 37.08, p < 0.001) and emotional distress scores (11.88 vs. 7.71, p < 0.001). Concern about test result (34.3% vs. 1.3%, p < 0.001), perceived risk compared to average women (55.4% vs. 14.1%, p < 0.001), and cancer worry (27.8% vs. 5.9%, p < 0.001) were also greater among HPV+ participants than participants testing HPV−. Participants testing HPV+ felt less reassured about their screening result than participants testing HPV− (16% vs. 75.1%, p < 0.001). Participants testing HPV+ had greater knowledge of HPV (11.96 vs. 10.36 out of 16, p < 0.001) and HPV testing (3.94 vs 3.28 out of 5, p < 0.001) than participants who reported testing HPV−.ConclusionsElevated levels of anxiety and emotional distress were found in those testing HPV+ compared with those testing HPV−. Future research should examine what strategies should be used to deliver test results and what additional information is provided, in order to alleviate anxiety among individuals testing HPV+.

Impact of a Human Papillomavirus Vaccination Program within Organized Cervical Cancer Screening: Cohort Study

Abstract Background: We assessed the effectiveness of an HPV (human papillomavirus) vaccination program in lowering cervical abnormality risk, and conferring herd protection. Methods: Retrospective cohort study using linked screening and vaccination administrative health data of the general population of Ancona Province, Italy. We included all female residents born in 1990–1993, eligible for catch-up HPV vaccination up to age 25 years, and adhering to organized screening in 2015–2020 (n = 4,665). Cervical abnormalities rates were compared between: Vaccinated and unvaccinated women, and cohorts with high and low vaccination uptake. Analyses were adjusted for age, country of birth, screening tests number, laboratory, and municipality average income. Main outcomes were ASC-US+ or LSIL+ Pap smears, and CIN1+ or CIN2+ histology. Results: Mean screening age was 26.6±1.5 years, and 1,118 screened women (24.0%) were vaccinated (mean vaccination age 19.2±1.5 years). The diagnosed cervical abnormalities were: 107 LSIL+ (2.3%), 70 CIN1+ (1.5%), and 35 CIN2+ (0.8%). The adjusted odds ratios of LSIL+, CIN1+, and CIN2+ among vaccinated versus unvaccinated women were, respectively: 0.55 [(95% confidence interval (CI), 0.33–0.91)], 0.43 (95% CI, 0.22–0.86), and 0.31 (95% CI, 0.11–0.91). Among the unvaccinated, those in the highest-uptake (45.3%) 1993 cohort, versus the last pre-vaccination 1990 cohort, showed AORs of LSIL+ and CIN1+ of 0.23 (95% CI, 0.10–0.50), and 0.22 (95% CI, 0.07–0.69), respectively. Conclusions: In the first evaluation from Central Italy, catch-up HPV vaccination considerably reduced the risk of all cervical abnormalities diagnosed within organized screening, and conferred an elevated degree of herd protection among unvaccinated women. Impact: The high protection conferred by HPV vaccination suggests the need to update cervical screening.

‘I’m a bit of a champion for it actually’: qualitative insights into practitioner-supported self-collection cervical screening among early adopting Victorian practitioners in Australia

Abstract Background: Self-collection for cervical screening has been available in the Australian National Cervical Screening Program since 2017 and is now available to all people as an option for cervical screening through a practitioner-supported model. Documenting early adopting practitioner experiences with self-collection as a mechanism to engage people in cervical screening is crucial to informing its continuing roll-out and implementation in other health systems. Aim: This study aimed to describe the experiences of practitioners in Victoria, Australia, who used human papillomavirus (HPV)-based self-collection cervical screening during the first 17 months of its availability. Methods: Interviews (n = 18) with practitioners from Victoria, who offered self-collection to their patients between December 2017 and April 2019, analysed using template analysis. Findings: Practitioners were overwhelmingly supportive of self-collection cervical screening because it was acceptable to their patients and addressed patients’ barriers to screening. Practitioners perceived that knowledge and awareness of self-collection were variable among the primary care workforce, with some viewing self-collection to be inferior to clinician-collected screening. Practitioners championed self-collection at an individual level, with the extent of practice-level implementation depending on resourcing. Concerns regarding supporting the follow-up of self-collected HPV positive patients were noted. Other practical barriers included gaining timely, accurate screening histories from the National Cancer Screening Register to assess eligibility. Practitioners’ role surrounded facilitating the choice between screening tests through a patient-centred approach.

Protocol for a cervical screening implementation trial comparing two approaches for delivering HPV self-collection in low-resource settings in India: a type 3 hybrid cluster randomised controlled trial (SHE-CAN)

Background Although multiple studies have offered self-collection for human papillomavirus (HPV)-based cervical screening in community settings, there are no randomised controlled trials (RCTs) that have compared implementation outcomes of programme approaches for self-collection. This trial will compare two such approaches in low-resource settings in the states of Tamil Nadu and Mizoram, India. Methods A cluster RCT will be conducted over a year, offering self-collection to 3000 women aged 30–49 from 28 clusters (average size 101) in selected districts. Clusters in tribal, rural and urban low-income settings will be randomised to two arms. The intervention arm, co-designed with multiple stakeholders, will involve campaigns to offer self-collection in the community. The comparison arm will be offered self-collection at the nearest health facilities. HPV-based cervical screening will be performed at central laboratories using clinically validated screening assays that can identify the highest risk carcinogenic HPV types (Group 1a–c - HPV16/18/31/33/45/52/58, ±35). Ablative treatment will be based on positivity with this extended genotyping triage, while those with any of the lower carcinogenic HPV types (Group 1d - 39, 51, 56, 59, ±35, Groups 2a/b - 66, 68) will undergo further assessment with visual inspection with acetic acid. Outcomes will be evaluated quantitatively and qualitatively using RE-AIM and the Theoretical Framework of Acceptability. Analysis The primary outcome will be percentage of women well-managed (screened and appropriately treated) in both arms, with secondary outcomes including proportion screened, proportion treated, acceptability (willingness to screen, rescreen, and/or recommend to others) to women, community and healthcare providers, adoption (by providers), implementation fidelity, costs, sustainability assessment and systematically identified implementation barriers and facilitators. The reach, effectiveness and acceptability of community-based self-collection and the use of extended genotyping for triage in resource-constrained, hard-to-reach populations will be assessed, with lessons that can inform future statewide and national programmes. Ethics and dissemination Ethics approval has been obtained from the Institutional Review Board (IRB) and Ethics Committee of the Christian Medical College Vellore, Tamil Nadu, India (IRB Min. No 14314; INTERVEN), the Alfred Hospital Ethics Committee (HREC Ref 80134, Local Reference: project 601/21), Melbourne, Australia, the IARC Ethics Committee (IEC 21-32), Lyon, France, the Salem Polyclinic Institutional Ethics Committee (SPCIEC/2022/June/01/02), Tamil Nadu, India and the Institutional Ethics Committee, Civil Hospital, Aizawl, Mizoram, India (No.B.12018/1/13-CHA(A)/IEC/115). The study is also approved by the State Scientific Advisory Committee, Directorate of Public Health and Preventive Medicine, Chennai, Tamil Nadu (R. No. 011575/HEB/A2/2023). The Alfred Hospital Approval, as an authorised Australian ethics committee for national mutual recognition, is recognised and registered with the University of Melbourne Human Research Ethics Committee (2024-25255-57650-1). Written informed consent will be obtained from participants. The results of the trial will be disseminated through a peer-reviewed medical journal, and also through workshops, reports and conferences. Trial registration number The trial has been registered with the Clinical Trials Registry - India: CTRI/2022/04/042327.

Readiness to transition to HPV self-collection from VIA screening: a mixed methods health systems assessment from Tamil Nadu, India

As a frontrunner in introducing cervical screening in India, the state of Tamil Nadu urgently needs to consider how to improve screening rates and switch to Human Papillomavirus (HPV) detection tests. We used a mixed methods design to assess the readiness of the state health system for delivering the current cervical screening program, as well as for future HPV self-collection. Following a desk review, we surveyed 14 government health facilities in three districts of Tamil Nadu and calculated overall and domain-specific (service utilization, service availability, general service, cervical screening) readiness scores as percentages. We conducted four interviews and five focus group discussions with 37 participants [managers, primary care nurses, community health workers (CHWs)] to clarify findings and obtain suggestions regarding the introduction of HPV self-collection in tribal, rural, and urban low-resource settings. Scores for general services and readiness to offer visual inspection with acetic acid (VIA) and follow-up were more than 70% in the surveyed facilities. Despite the availability of trained nurses, infrastructure and resources, utilisation was primarily limited to symptomatic women attending health facilities due to poor acceptability of screening that would require facility visits. Most participants felt that self-collection could reduce women's fear and embarrassment and could be delivered through CHWs in the community or by nurses at facilities. However, motivation for screening may remain low as most asymptomatic women do not perceive a need for screening, and/or fear implications of a positive test. Tertiary laboratories appear ready for HPV testing, given availability of high-throughput PCR equipment, computerised laboratory information management systems, and a planned hub and spoke model of improving access to laboratory tests. Despite relatively good infrastructure and staffing for VIA screening in public healthcare facilities, service utilisation was primarily by symptomatic women, contributing to low screening rates. HPV self-collection was highly acceptable to administrative and field staff. Widespread educational approaches to motivate asymptomatic women to screen using self-collection, with decentralised sample collection and treatment, could potentially improve cervical screening rates. Not applicable.