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HELSEVEL-H-Gode og effektive helse-, omsorgs- og velferdstjenester

Improving clinical practice and national guidelines: A comparative effectiveness study of prevention strategies for HPV-related conditions

Alternative title: Forbedring av klinisk praksis og nasjonale retningslinjer: Studier av tiltak for å forebygge HPV-relatert sykdom

Awarded: NOK 7.3 mill.

In Norway, new screening technologies can improve the effectiveness and efficiency of cervical cancer screening. Mailing self-sampling device kits to all women non-compliant to screening within a 5-year or 10-year period can be more effective and less costly than the current reminder letter policy; however, the optimal self-sampling strategy is dependent on the profile and behavior of respondents, which needs to be considered prior to selecting and implementing a self-sampling policy. In addition, novel approaches to HPV DNA testing or candidate biomarkers may improve management of women with minor cervical lesions, yet are accompanied by a trade-off of increased follow-up procedures. The optimal strategy therefore depends on decision-makers willingness to accept higher monetary and non-monetary resource use, as well as local capacity constraints. Norwegian health authorities are currently evaluating replacing cytology with HPV DNA testing in primary cervical cancer screening starting at age 34 years. To maximize the prevention of cervical cancer, however, primary HPV DNA testing should start at an earlier age, and the number of follow-up procedures can be moderated by less intensive follow-up of women who are HPV-positive and cytology-negative. Although almost 70% of women in screening target age have attended cervical cancer screening in Norway within 3.5 years, the proportion who attends screening every 3 years (as recommended) is considerably lower. A registry-based study using population-based data from two decades of screening in Norway shows that only 46% of screen-eligible women attend routine screening, and the majority of these attend screening more frequently than recommended. Screening behavior is associated with cancer outcomes; cervical cancer incidence (as well as the proportion of cancer cases diagnosed at a more advanced stage) was higher among women who never or seldom attended screening than those attending regularly. In general, we have found that in Norway, new screening technologies can improve the effectiveness and efficiency of cervical cancer screening. Mailing self-sampling device kits to all women non-compliant to screening within a 5-year or 10-year period can be more effective and less costly than the current reminder letter policy; however, the optimal self-sampling strategy is dependent on the profile and behavior of respondents, which needs to be considered prior to selecting and implementing a self-sampling policy. In addition, novel approaches to HPV DNA testing or candidate biomarkers may improve management of women with minor cervical lesions, yet are accompanied by a trade-off of increased follow-up procedures. The optimal strategy therefore depends on decision-makers willingness to accept higher monetary and non-monetary resource use, as well as local capacity constraints. Norwegian health authorities are currently evaluating replacing cytology with HPV DNA testing in primary cervical cancer screening starting at age 34 years. To maximize the prevention of cervical cancer, however, primary HPV DNA testing should start at an earlier age, and the number of follow-up procedures can be moderated by less intensive follow-up of women who are HPV-positive and cytology-negative. Although almost 70% of women in screening target age have attended cervical cancer screening in Norway within 3.5 years, the proportion who attends screening every 3 years (as recommended) is considerably lower. A registry-based study using population-based data from two decades of screening in Norway shows that only 46% of screen-eligible women attend routine screening, and the majority of these attend screening more frequently than recommended. Screening behavior is associated with cancer outcomes; cervical cancer incidence (as well as the proportion of cancer cases diagnosed at a more advanced stage) was higher among women who never or seldom attended screening than those attending regularly. In the United States, HPV vaccines are expected to reduce the overall burden of HPV-associated cancers for all racial/ethnic groups and to reduce the absolute disparity gap. However, even with improved coverage with the second-generation vaccine, relative disparities will likely still exist and may widen if the underlying causes of these disparities remain unaddressed. Moreover, in HPV-vaccinated women, a model-based analysis suggests US screening can be modified to start at later ages, occur at decreased frequency, and involve primary HPV testing in HPV-vaccinated women, providing more health benefit at lower harms and costs than current screening guidelines. As increasing cohorts of HPV-vaccinated women enter screening age, the revision of cervical cancer screening guidelines will be important. Lastly, a model-based analysis indicates that most women (i.e., 75%) who develop cervical cancer acquired their "causal" HPV infection by age 31 years, which limits prevention opportunities.

This project has identified several screening and vaccination strategies and assisted Norwegian society in developing better and more efficient policies for prevention of HPV-related diseases. These policies include, for example, new screening guidelines for women aged 25-33 years (implemented July 2018), policy recommendation to stratify screening guidelines by HPV vaccination status, policy recommendation to implement self-sampling for underscreened women. We have also estimated the total burden of HPV-related cancers in Norway, and highlighted that, while many women attend cervical cancer screening in Norway, most women do not attend regularly according to guidelines. We have worked closely with the Cancer Registry of Norway (including sitting on two advisory guidelines groups) to inform the delivery of preventive health services that maximize prevention of cervical cancer while simultaneously provide efficient use of health care resources.

Significant advances have occurred in our understanding of human papillomavirus (HPV), a common sexually-transmitted infection. Persistent infection with HPV is the causal agent for several genital (e.g., cervical cancer (CC)) and oral cancers, and most genital warts. Yet there are critical challenges in reducing HPV-related morbidity and mortality. Through strong international collaboration and the involvement of key stakeholders in Norway, we aim to optimize HPV-vaccination policy, increase screening participation rates, tailor diagnostic work-up of women with abnormal screening results, and establish evidence for the effectiveness and cost-effectiveness of anal cancer screening in Norway. We will use a multidisciplinary approach, including mathematical modeling, registry-based analyses and economic evaluation to refine clinical practice to influence national guidelines. Subproject 1 will estimate the economic burden and disparities within the treatment of HPV-related cancers and estimate the cost-effectiveness of vaccinating female cohorts with the forthcoming 2nd generation HPV vaccine. Subproject 2 will 1) characterize the historical trends for CC screening participation, 2) use randomized trial data to assess the cost-effectiveness of self-sampling for women with sub-optimal screening attendance, 3) investigate the risk of cervical cancer by degree of screening participation 4) investigate the cost-effectiveness of alternative strategies to improve diagnostic work-up of women with abnormal screening results. Finally, subproject 3 will explore the use of new diagnostics to determine whether primary screening of anal cancer among high-risk groups is considered effective and cost-effective in the US and Norway. Cumulatively, these projects will inform the efficient delivery of preventive health services that maximize health across multiple types of cancer, among both women and men, which are related to an infection with HPV.

Funding scheme:

HELSEVEL-H-Gode og effektive helse-, omsorgs- og velferdstjenester