Implementation considerations using HPV self-collection to reach women under-screened for cervical cancer in high-income settings

Commentary

Implementation considerations using HPV self-collection to reach women under-screened for cervical cancer in high-income settings


H.N. Pedersen, MPH*, L.W. Smith, RN(C) BN MPH, C. Sarai Racey, MPH PhD, D. Cook, MSc SCCM§, M. Krajden, MD FRCPC§, D. van Niekerk, MB ChB Mmed FFPath LMCC FRCPC§, G.S. Ogilvie, MD MSc FCFP DrPH*



doi: http://dx.doi.org/10.3747/co.25.3827

PARADIGM SHIFT TOWARDS HPV SCREENING GLOBALLY

The success of cytology (Pap screening) programs is undeniable and has drastically reduced cervical cancer rates in high-income settings where it has been implemented1. However, cytology for primary cervical cancer screening has a number of limitations including poor sensitivity, a taxing demand on human and operational infrastructure, high health system costs, and limited uptake rates, leading researchers and policy-makers to question whether further gains in public health are possible using this approach2. Persistent infection with high-risk genotypes of human papillomavirus (hpv) is well established as the necessary cause for development of cervical cancer3. Research has shown a 30% improvement in sensitivity in detecting high-grade lesions, cervical squamous intraepithelial neoplasia (cin) grade 2 or greater (cin2+), can be achieved with high-risk hpv dna testing compared with cytology4. A negative hpv test confers two-fold greater reassurance against the development of cervical cancer over three years compared with a negative cytology test2,5. The Netherlands has recently transitioned from cytology to hpv testing for primary cervical cancer screening in their National program. Many organized screening programs intend to implement primary hpv screening69, including Australia, which will begin implementation in December 2017.

A consistent barrier to cytology-based cervical cancer screening is non-attendance, which can be addressed through hpv testing using self-collected samples. Primary cervical cancer screening with hpv dna testing allows for the opportunity of self-collected samples, which is not possible with cytology. In hpv self-collection the sample is obtained vaginally by the woman herself, using a device such as a swab or brush. The swab is subsequently tested for high-risk strains of hpv in a laboratory. With this approach to screening, programs can mail self-collection kits directly to women who are overdue for screening as an alternative to a clinic-based visit. Self-collected cervical samples receiving hpv testing show comparable cin2+ sensitivity compared with clinician-collected samples tested with cytology and with hpv1012. Self-collection has proven to be highly acceptable among women13.

Human papillomavirus self-collection has the potential to overcome many of the personal and system-level barriers to screening that exist for cytology or other clinic-based screening methods. Some women, particularly those who have experienced abuse14 or are otherwise marginalized, may find self-sampling preferable because of such things as cultural/religious embarrassment or discomfort associated with a pelvic exam13,1517. Time, transportation, inconvenient clinic hours, or not having a regular practitioner are also relevant factors associated with under-screening that can be mitigated through hpv self-collection using mailed samples13,16,17. However, there are psychosocial barriers to hpv screening, including women’s lack of awareness and fears around hpv and cervical cancer screening, which cannot be addressed through self-collection-based screening alone17,18.

USING HPV SELF-COLLECTION TO REACH UNDER-SCREENED WOMEN

Globally, it is women who do not attend cervical cancer screening that are at highest risk for severe cervical dysplasia and cervical cancer19. In countries with publicly funded cervical cancer screening programs, irregular attendance or non-attendance to screening is one of the key barriers to further reducing cervical cancer rates19,20. Lower screening rates have been reported in specific populations, such as immigrant women, women of low socio-economic status, and Indigenous women21,22. The acceptability and feasibility of screening using hpv self-collection to reach under-served women has been demonstrated in street-involved or otherwise marginalized women 23, rural communities24, and Indigenous communities in Canada25; however, these evaluations were conducted as smaller research projects and did not consider the implications for scaling up to a program level.

At a population level, hpv self-collection has been used in large-scale randomized controlled trials to reach under-screened women in settings where further gains in screening coverage with cytology have plateaued2628. A recent systematic review and meta-analysis reported that hpv self-screening with home kits significantly improved pooled participation in cervical cancer screening by double, compared with invitations to attend cytology29. By shifting screening to a non-clinical setting, self-collection can improve access to screening10 among women who face barriers to clinic-based screening, and it offers a patient-centred approach that may improve engagement with screening30. Despite generally high acceptability of self-collection, some women expressed concerns of sampling accuracy and a lack of confidence in collecting the sample correctly30. Perceptions of low self-efficacy to perform the test can negatively impact women’s attitudes towards using self-sampling31, underscoring the need for health education as part of an implementation plan. Additional studies conducted in Australia28, Denmark26, Sweden32, and Norway33 largely recommend the use of self-collected hpv screening to increase participation in screening among under-screened populations. What is less clear is how best to operationalize this approach into existing health care systems.

CONSIDERATIONS FOR IMPLEMENTATION

There are different approaches to offering self-collection-based screening to non-attenders that have been tested in various countries29. The hpv-based screening program in the Netherlands is attempting to reach a higher number of non-attenders by using an opt-out approach in which self-collection kits are directly mailed to under-screened women, often after a reminder letter. Modelling has shown that this method will improve the effectiveness of a primary hpv screening-based program in a cost-effective manner, provided that sensitivity remains high and the program can sufficiently reach under-screened women34. A significant threat to this approach is that in practice, uptake rates have been highly variable (between 6.4% and 34%)29 and there is significant waste and cost associated with unused kits35. In a research setting, large trials have used door-to-door recruitment, where community health workers offer sampling to eligible women at their homes, yielding participation rates higher than 90%29; however, this is resource intensive and not feasible in many settings. In an opt-in approach, under-screened women are invited to request a kit to their homes, either by phone or through a digital system such as a website26. This approach assumes that there are fewer wasted kits, but it could result in lower gains in population coverage, and in some studies, opt-in hpv screening did not demonstrate a significant improvement over invitation letters to cytology29. Alternative self-collection strategies may need to be evaluated to identify optimal approaches in different population settings.

HEALTH CARE SYSTEM CONSIDERATIONS

Cytology-based cervical cancer screening via a clinician is an important entry point to health care for many women and offers the opportunity for clinicians to provide more comprehensive reproductive health services and counselling such as testing for sexually transmitted infections and family planning36. In settings with established screening programs, hpv self-collection is recommended to complement, not replace, existing programs, as an approach to reach under-served women. Research has shown good attendance to follow-up with a health care provider among women who screen hpv-positive with self-collection37, suggesting self-collection could potentially act as a re-entry point for women into the screening program or health care system. However, for marginalized women or women who lack access, the follow-up necessary for an hpv-positive result, which usually takes place in a clinic setting, could be a barrier, and these women are at higher risk for developing cervical cancer35.

Using hpv self-collection to reach marginalized and never-screened women presents both opportunities and challenges, including offering it in an outreach setting23. Health care services for street-involved women are often provided by nurses and nurse practitioners who may not be trained, or have the infrastructure, time, or capacity to offer Pap screening. Human papillomavirus self-collection is ideal in these settings; however, consideration should be given to how screening records will be maintained. Ideally, all cervical cancer screening records, including hpv screening, would be kept in a centralized registry. Access to electronic health records may not always be available during outreach care, presenting challenges to appropriately track and follow up women and maintain their screening history.

To prevent over-screening and truly reach those who do not attend, it will be important for programs to consider having systems in place to verify whether women are already up to date and engaged in screening. Particularly as women vaccinated against high-risk hpv types mature and coverage increases, close evaluation and cost-effectiveness should be considered38. The high sensitivity of high-risk hpv tests will inevitably detect transient infections that would otherwise resolve without the need for treatment, especially among young women aged 25 to 3439. This could lead to excessive referral to colposcopy, biopsy, and treatment40, which is not only a burden and cost to the health care system but can be harmful to women38,4143. For these reasons, the recommended age to start screening (between 25 and 30 years) is older with hpv screening than with cytology. The screening interval between hpv tests is also longer (4 to 5 years)5,6 because a negative hpv test provides greater reassurance than negative cytology. Studies have noted that women’s concerns about an extended screening interval for hpv could affect the acceptability of hpv screening44,45. This stems from the misconception that the longer interval could result in missed detection of pre-cancerous lesions, and it could lead to over-screening if women present for screening more frequently46. Regional guidelines on screening interval, age of screening commencement, and appropriate triage pathways, coupled with comprehensive education and dissemination throughout the health care system play an important role in mitigating over-screening. However, in order for hpv-based screening to be optimized, practitioners will need to be adequately educated on how to manage hpv-positive results and equipped with messaging to handle concerns and questions women may have about hpv, given recommendations from physicians and other clinicians are known to influence patient behaviours47. Physician education should include strategies to address adverse emotional responses women may have when informed they have an hpv infection48.

In the era of primary hpv screening for cervical cancer, self-collection is a powerful tool that can be used to increase screening coverage among under-served and under-screened women. Human papillomavirus self-collection should be implemented with careful consideration to the local context, in coordination with various sectors of the health care system, and coupled with careful evaluation.

CONFLICT OF INTEREST DISCLOSURES

We have read and understood Current Oncology’s policy on disclosing conflicts of interest, and we declare that we have none.

AUTHOR AFFILIATIONS

*University of British Columbia, Vancouver, BC;, Women’s Health Research Institute, Vancouver, BC;, BC Cancer Agency, Vancouver, BC; and, §BC Centre for Disease Control, Vancouver, BC..

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Correspondence to: Gina Ogilvie, BC Women’s Hospital + Health Centre, Box 42, 4500 Oak Street, Vancouver, British Columbia V6H 3N1. E-mail: gina.ogilvie@cw.bc.ca

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Current Oncology, VOLUME 25, NUMBER 1, February 2018








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