Iacopo Baussano

Leveraging single-dose human papillomavirus vaccination dose-efficiency to attain cervical cancer elimination in resource-constrained settings

Abstract Background In low- and middle-income countries, resource constraints remain a critical factor limiting access to cervical cancer preventive measures. The option of single-dose immunization could help improve access to human papillomavirus vaccination and attain cervical cancer elimination. Methods With simulation models adapted to country-specific data and scenarios for single-dose protection derived from International Agency for Research on Cancer India vaccine trial data, we estimated the expected impact of single-dose vaccination in India, Rwanda, and Brazil, three countries with varying profiles of cervical cancer risk and vaccination timelines. In combination with single-dose vaccination, we explored different resource reallocation strategies based on dose efficiency, elimination attainment, and cervical cancer cases prevented, with the existing 2-dose program as a comparator. Results Assuming lifelong single-dose protection, switching from 2-dose to 1-dose vaccination and reallocating resources to female catch-up could prevent 467-1336, 94-194, and 15-207 additional cervical cancer cases (per 100 000 women born) in cohorts aged 11-30 years in India, Rwanda, and Brazil, respectively. Resource reallocation to improve the current routine coverage could help eliminate cervical cancer in India and across all Brazilian states but not in Rwanda. For each country, we found a dose-efficient reallocation strategy (or a combination of strategies) together with 1-dose vaccination that could prevent more cervical cancers vs 2-dose vaccination, even in the worst-case scenario of single-dose protection. Conclusion Adopting single-dose vaccination with resource reallocation is a resource-efficient approach to enhance progress toward cervical cancer elimination. The overall impact of vaccination can be maximized by fine-tuning resource reallocation to a country’s needs.

Toward a Framework to Assess the Financial and Economic Burden of Cervical Cancer in Low- and Middle-Income Countries: A Systematic Review

PURPOSE To review the economic burden assessment of cervical cancer in low- and middle-income countries (LMICs) and use the findings to develop a pragmatic, standardized framework for such assessment. METHODS We first systematically reviewed articles indexed in scientific databases reporting the methodology for collecting and calculating costs related to the cervical cancer burden in LMICs. Data on study design, costing approach, cost perspective, costing period, and cost type (direct medical costs [DMC], direct nonmedical costs [DNMC], and indirect costs [IC]) were extracted. Finally, we summarized the reported limitations in the methodology and used the solutions to inform our framework. RESULTS Cervical cancer treatment costs across LMICs vary greatly and can be extremely expensive, up to 70,968 International US dollars. Economic and financial assessment methods also vary greatly across countries. Of the 28 reviewed articles, 25 studies reported DMC for cervical cancer treatment by extracting cost information from billing or insurance databases (eight studies), conducting surveys (five), and estimating the costs (12). Only 11 studies—mainly through surveys—reported DNMC and IC. The economic burden assessment framework includes health care/payer and societal perspectives (DMC, DNMC, IC, and human capital loss) across the cervical cancer screening and treatment continuum. To assess health care/payer costs, we recommend combining the predefined treatment standards with actual local treatment practices, multiplied by unit costs. To assess societal costs, we recommend conducting a cost survey in line with a standardized yet adaptable protocol. CONCLUSION Our standardized, pragmatic framework allows assessment of economic and financial burden of cervical cancer in LMICs despite the different levels of available resources across countries. This framework will facilitate global comparisons and monitoring and may also be applied to other cancers.

Human papillomavirus genotypes in cervical and other HPV‐related anogenital cancer in Rwanda, according to HIV status

The study aim was to describe human papillomavirus (HPV)‐attributable cancer burden in Rwanda, according to anogenital cancer site, HPV type, age and HIV status. Tissue specimens of cervical, vulvar, vaginal, penile and anal cancer diagnosed in 2012–2018 were retrieved from three cancer referral hospitals and tested for high‐risk (HR) HPV DNA. Cervical cancer represented the majority of cases (598 of 738), of which 96.0% were HR‐HPV positive. HPV‐attributable fractions in other cancer sites varied from 53.1% in 81 penile, through 76.7% in 30 vulvar, 83.3% in 24 vaginal, up to 100% in 5 anal cases. HPV16 was the predominant HR‐HPV type in cervical cancer (55.0%), followed by HPV18 (16.6%) and HPV45 (13.4%). HPV16 also predominated in other cancer sites (60–80% of HR‐HPV‐attributable fraction). For cervical cancer, type‐specific prevalence varied significantly by histology (higher alpha‐9 type prevalence in 509 squamous cell carcinoma vs. higher alpha‐7 type prevalence in 80 adenocarcinoma), but not between 501 HIV‐negative and 97 HIV‐positive cases. With respect to types targeted, and/or cross‐protected, by HPV vaccines, HPV16/18 accounted for 73%, HPV31/33/45/52/58 for an additional 22% and other HR‐HPV types for 5%, of HPV‐attributable cancer burden, with no significant difference by HIV status nor age. These data highlight the preventive potential of the ongoing national HPV vaccination program in Rwanda, and in sub‐Saharan Africa as a whole. Importantly for this region, the impact of HIV on the distribution of causal HPV types was relatively minor, confirming type‐specific relevance of HPV vaccines, irrespective of HIV status.

Baseline findings and safety of infrequent vs. frequent screening of human papillomavirus vaccinated women

Less frequent cervical cancer screening in human papillomavirus (HPV) vaccinated birth cohorts could produce considerable savings without increasing cervical cancer incidence and loss of life‐years. We report here the baseline findings and interim results of safety and accuracy of infrequent screening among HPV16/18 vaccinated females. The entire 1992–1994 birth‐cohorts (30,139 females) were invited to a community‐randomized HPV16/18‐vaccination trial. A total of 9,482 female trial participants received HPV16/18‐vaccination in 2007–2009 at age of 13–15. At age 22, 4,273 (45%) of these females consented to attend a randomized trial on frequent (ages 22/25/28; Arm 1: 2,073 females) vs. infrequent screening (age 28; Arm 2: 2,200 females) in 2014–2017. Females (1,329), who had got HPV16/18 vaccination at age 18 comprised the safety Arm 3. Baseline prevalence and incidence of HPV16/18 and other high‐risk HPV types were: 0.5% (53/1,000 follow‐up years, 104) and 25% (2,530/104) in the frequently screened Arm 1; 0.2% (23/104) and 24% (2,413/104) in the infrequently screened Arm 2; and 3.1% (304/104) and 23% (2,284/104) in the safety Arm 3. Corresponding prevalence of HSIL/ASC‐H and of any abnormal cytological findings were: 0.3 and 4.2% (Arm 1), 0.4 and 5.3% (Arm 2) and 0.3 and 4.7% (Arm 3). Equally rare HSIL/CIN3 findings in the infrequently screened safety Arm A3 (0.4%) and in the frequently screened Arm 1 (0.4%) indicate no safety concerns on infrequent screening despite the up to 10 times higher HPV16/18 baseline prevalence and incidence in the former.

Age‐specific burden of cervical cancer associated with HIV: A global analysis with a focus on sub‐Saharan Africa

AbstractHIV substantially worsens human papillomavirus (HPV) carcinogenicity and contributes to an important population excess of cervical cancer, particularly in sub‐Saharan Africa (SSA). We estimated HIV‐ and age‐stratified cervical cancer burden at a country, regional and global level in 2020. Proportions of cervical cancer (a) diagnosed in women living with HIV (WLHIV), and (b) attributable to HIV, were calculated using age‐specific estimates of HIV prevalence (UNAIDS) and relative risk. These proportions were validated against empirical data and applied to age‐specific cervical cancer incidence (GLOBOCAN 2020). HIV was most important in SSA, where 24.9% of cervical cancers were diagnosed in WLHIV, and 20.4% were attributable to HIV (vs 1.3% and 1.1%, respectively, in the rest of the world). In all world regions, contribution of HIV to cervical cancer was far higher in younger women (as seen also in empirical series). For example, in Southern Africa, where more than half of cervical cancers were diagnosed in WLHIV, the HIV‐attributable fraction decreased from 86% in women ≤34 years to only 12% in women ≥55 years. The absolute burden of HIV‐attributable cervical cancer (approximately 28 000 cases globally) also shifted toward younger women: in Southern Africa, 63% of 5341 HIV‐attributable cervical cancer occurred in women <45 years old, compared to only 17% of 6901 non‐HIV‐attributable cervical cancer. Improved quantification of cervical cancer burden by age and HIV status can inform cervical cancer prevention efforts in SSA, including prediction of the impact of WLHIV‐targeted vs general population approaches to cervical screening, and impact of HIV prevention.

Building resilient cervical cancer prevention through gender-neutral HPV vaccination

The COVID-19 pandemic has disrupted HPV vaccination programmes worldwide. Using an agent-based model, EpiMetHeos, recently calibrated to Indian data, we illustrate how shifting from a girls-only (GO) to a gender-neutral (GN) vaccination strategy could improve the resilience of cervical cancer prevention against disruption of HPV vaccination. In the base case of 5-year disruption with no coverage, shifting from GO to GN strategy under 60% coverage (before disruption) would increase the resilience, in terms of cervical cancer cases still prevented in the disrupted birth cohorts per 100,000 girls born, by 2.8-fold from 107 to 302 cases, and by 2.2-fold from 209 to 464 cases under 90% coverage. Furthermore, shifting to GN vaccination helped in reaching the World Health Organization (WHO) elimination threshold. Under GO vaccination with 60% coverage, the age-standardised incidence rate of cervical cancer in India in the long term with vaccination decreased from 11.0 to 4.7 cases per 100,000 woman-years (above threshold), as compared to 2.8 cases (below threshold) under GN with 60% coverage and 2.4 cases (below threshold) under GN with 90% coverage. In conclusion, GN HPV vaccination is an effective strategy to improve the resilience to disruption of cancer prevention programmes and to enhance the progress towards cervical cancer elimination.

Approximating missing epidemiological data for cervical cancer through Footprinting: A case study in India

Local cervical cancer epidemiological data essential to project the context-specific impact of cervical cancer preventive measures are often missing. We developed a framework, hereafter named Footprinting, to approximate missing data on sexual behaviour, human papillomavirus (HPV) prevalence, or cervical cancer incidence, and applied it to an Indian case study. With our framework, we (1) identified clusters of Indian states with similar cervical cancer incidence patterns, (2) classified states without incidence data to the identified clusters based on similarity in sexual behaviour, (3) approximated missing cervical cancer incidence and HPV prevalence data based on available data within each cluster. Two main patterns of cervical cancer incidence, characterized by high and low incidence, were identified. Based on the patterns in the sexual behaviour data, all Indian states with missing data on cervical cancer incidence were classified to the low-incidence cluster. Finally, missing data on cervical cancer incidence and HPV prevalence were approximated based on the mean of the available data within each cluster. With the Footprinting framework, we approximated missing cervical cancer epidemiological data and made context-specific impact projections for cervical cancer preventive measures, to assist public health decisions on cervical cancer prevention in India and other countries.

Scientific approaches toward improving cervical cancer elimination strategies

AbstractAt the 2023 EUROGIN workshop scientific basis for strategies to accelerate the elimination of cervical cancer and its causative agent, human papillomavirus (HPV) were reviewed. Although some countries have reached key performance indicators toward elimination (>90% of girls HPV vaccinated and >70% of women HPV screened), most are yet to reach these targets, implying a need for improved strategies. Gender‐neutral vaccination, even with moderate vaccination coverage was highlighted as a strategy to achieve elimination more rapidly. It is more resilient against major disturbances in vaccination delivery, such as what happened during the coronavirus pandemic. Further, an analysis of ethical/legal issues indicated that female‐restricted vaccination is problematic. Extended catch‐up of vaccination with concomitant screening, and outreach to vulnerable groups were highlighted. Although birth cohorts with high coverage of HPV vaccination at school are protected against HPV, and HPVs have a very low reproductive rate in women above age 35, adult women below age 30 have inadequate direct protection. In addition to herd protection from gender‐neutral vaccination, this group can be protected by offering concomitant catch‐up HPV vaccination and HPV screening. Furthermore, hepatitis B vaccination experiences indicate that elimination cannot be achieved without prioritizing vulnerable/migrant populations. The long‐lasting durability of vaccination‐induced antibody responses suggests prolonged protection with HPV vaccines when adequately administrated. Finally, cost‐effectiveness modelling suggests that high‐coverage HPV vaccination in multiple population segments will be resource‐saving due to reduced need for screening. In summary, the workshop found that strategically optimal deployment of vaccination will accelerate elimination of HPV and cervical cancer.