J. Andrew Dykens
Caryn E. Peterson
Hunter K. Holt
Diane M. Harper- 1Department of Family and Community Medicine, College of Medicine, University of Illinois Chicago, Chicago, IL, United States
- 2Center for Global Health, College of Medicine, University of Illinois Chicago, Chicago, IL, United States
- 3Cancer Center, College of Medicine, University of Illinois Chicago, Chicago, IL, United States
- 4Division of Epidemiology and Biostatistics, School of Public Health, University of Illinois Chicago, Chicago, IL, United States
- 5Department of Family Medicine, School of Medicine, University of Michigan, Ann Arbor, MI, United States
- 6Department of Obstetrics & Gynecology, School of Medicine, University of Michigan, Ann Arbor, MI, United States
- 7Department of Women's Studies, College of Literature, Science and the Arts, University of Michigan, Ann Arbor, MI, United States
Human papillomavirus (HPV) infection is responsible for many cancers in both women and men. Cervical cancer, caused by HPV, is the fourth most common cancer among women worldwide, even though it is one of the most preventable cancers. Prevention efforts include HPV vaccination, however these programs remain nascent in many countries. In 2020 the World Health Assembly adopted the Global Strategy for cervical cancer elimination including a goal to fully vaccinate 90% of girls with the HPV vaccine by the age of 15. However, very few countries have reached even 70% coverage. Increased vaccine availability in the future may allow the opportunity to vaccinate more people. This could add to the feasibility of introducing gender-neutral HPV vaccination programs. Adopting a gender-neutral HPV vaccine approach will reduce HPV infections transmitted among the population, combat misinformation, minimize vaccine-related stigma, and promote gender equity. We propose approaching programmatic research through a gender-neutral lens to reduce HPV infections and cancers and promote gender equality. In order to design more effective policies and programs, a better understanding of the perspectives of clients, clinicians, community leaders, and policy-makers is needed. A clear, multi-level understanding of these stakeholders' views will facilitate the development of target policy and programs aimed at addressing common barriers and optimizing uptake. Given the benefit of developing gender-neutral HPV vaccination programs to eliminate cervical cancer and address other HPV associated cancers, we must build knowledge through implementation research around this topic to inform policy-makers and funders for future policy shifts.
Introduction
Human papillomavirus (HPV) affects both women and men and is the most common sexually transmitted infection in the world (1). There are more than 100 HPV types of which 13 are classified as oncogenic. HPV is highly prevalent globally, with an estimated 80%−90% of women and men acquiring infection in their lifetime (2, 3). Oncogenic HPV types are responsible for anogenital and cutaneous warts and several cancers including oropharyngeal, anogenital, cervical, anal, vulvar, vaginal, and penile (1).
Cervical cancer is the predominant HPV-related cancer and is the fourth most common cancer among women worldwide, despite effective prevention strategies (4). Global estimates show that cervical cancer occurred in 604,127 new cases and led to 341,831 deaths in 2020 (5). It is the most common type of cancer-related mortality among women in 42 countries, the majority living in Sub-Saharan Africa (4).
While cervical cancer incidence rates are declining or stagnating in high-income countries, the absolute number of cases continue to rise in low- and lower-middle-income countries (LMIC) (4). Models show that cervical cancer burden will increase by 17% to 708,000 cases and mortality will increase by 42% to 442,926 deaths in the year 2030 (6, 7). The most significant rise will be in LMICs, where 84% of incident cervical cancer cases and 90% of cervical cancer deaths occur (4).
Virtually all cases of invasive cervical cancer are caused by infection with high-risk (oncogenic) HPV infection types (8). Most infections (90%) are cleared through a normal immune-response within 1 year, with ~10% of all infections with an oncogenic HPV type progressing to a precancer or invasive cervical cancer (9). HPV 16 and 18 are responsible for about 70% of cervical cancer worldwide (10) while >90% of cases worldwide are caused by HPV types 16, 18, 31, 33, 45, 52, and 58 (11).
The higher rates of cervical cancer incidence and mortality in LMICs is attributable to the relative lack of high-quality cervical cancer screening and lack of widespread high-quality treatment of preinvasive/invasive cervical cancer in LMICs rather than significant differences in HPV infection rates (12). Higher rates, however, do not appear to be broadly associated with differences in cervical infection with oncogenic HPV types (10) (though there are higher rates of HPV among women infected with human immunodeficiency virus).
HPV vaccination programs remain nascent in several countries, particularly LMICs. Globally, there are 122 World Health Organization (WHO) countries and territory member states, and 27 non-members with HPV vaccination on the national routine immunization schedule. As of 2022, eight of 29 (28%) low-income countries and 22 of 51 (43%) lower-middle income countries had introduced HPV vaccine programs (13). Meanwhile, 72% of low-income countries and 57% of lower-middle income countries are yet to include HPV vaccination into their national immunization programs (14). Cost is a significant factor in a country's ability to initiate and maintain a program (15). The actual cost of the vaccine, which increases over time, initially accounts for 51% of total program costs (16). Other direct medical costs which tend to decrease over time include cold chain, workforce education, monitoring and evaluation, community education, and vaccination campaigns (14, 17).
Current global HPV vaccination program guidance and progress
In 2020 the World Health Assembly adopted the Global Strategy for the Elimination of Cervical Cancer. This strategy includes targets for HPV vaccination, and cervical cancer screening and treatment. Specifically, that 90% of girls will be fully vaccinated by the age of 15; that 70% of women will be screened using a high-performance test by the age of 35, and again by the age of 45; and that 90% of women with pre-cancer or invasive cancer will be treated or managed. Achieving these targets by 2030 will ensure that all countries reach and maintain a cervical cancer incidence rate of below four per 100,000 women (10).
Many transmission-dynamic models developed by the WHO Cervical Cancer Elimination Modeling Consortium show that 70% coverage through a girls-only HPV vaccination approach at 15 years of age leads to disease reduction (18). However, very few countries have reached 70% coverage. LMIC HPV vaccination coverage is 16% (8%−31% among 51 countries) for the first dose and 12% (5%−24% in 43 countries) for the second dose. Likewise, in Gavi eligible countries in 2018 (14 countries), 12% (4%−32%) of the population received one dose, and 7% (1%−21%) received the second dose in six countries (19). Based on these deficient coverage levels, neither disease reduction nor herd immunity will occur. In order to bolster the beneficial effects of the HPV vaccine, we must consider a gender-neutral approach. Recent models have shown that vaccinating boys in an environment of female coverage below 50% may be cost-effective, depending upon the prevalence of HPV-related disease and available resources (20). In addition, a systematic review that primarily included studies from high income countries showed that as long as vaccine price remained low, a gender neutral vaccination program was cost-effective if coverage was low. The same review did reinforce earlier findings that gender-neutral vaccination was less cost-effective than when targeting only girls aged 9–18 years if coverage for females was above 75% (21), however achieving this level of coverage in some LMICs is challenging.
The WHO has recently expanded recommended ages among females and added males within a secondary target group for HPV vaccination (22). Of the 141 global HPV vaccination programs, there are 43 countries and 4 territories that have gender-neutral HPV vaccine schedules (23). All of these programs are in high income countries and upper middle-income countries (19) except for a single program. Bhutan became the first LMIC and the first country in South East Asia to adopt gender-neutral vaccination policy in September 2020 (24).
Female-only HPV vaccination programs have several shortcomings (25) including the consideration of only cervical cancer as a HPV transmission outcome (21) and multiple additional assumptions: (1) of monogamy or serial monogamy with few lifetime partners without the consideration of polygamous societies (20); (2) of heterosexual relationships, thus discounting the potential for HPV spread through bisexual contact and by way of men who have sex with men (26); (3) of penile-vaginal intercourse, thus minimizing the consideration of digital and oral spread of HPV; (4) of the presence of gender equity without consideration of women's structural barriers (such as lack of autonomy, early marriages, and lack of education); and (5) of a uniform geographic and other social determinant acceptability of HPV vaccination. These assumptions may contribute to inequities as well as mistrust and misinformation.
One dose HPV vaccination approach
There is mounting evidence that a one-dose approach may prove effective (27–32). Currently, ongoing studies (33) through the Costa Rica Vaccine Trial (31), a multicenter cohort study in India (32), and the industry-sponsored PATRICIA trial (28) will inform future guidelines. Recently, The WHO Strategic Advisory Group of Experts on Immunization (SAGE) recommended updating the dosing schedule to one or two doses for girls aged 9–14 and women 15–20 years and concluded that a single dose is comparable to a 2-dose schedule (34). Compared with a two-dose HPV vaccination schedule, one-dose HPV vaccination could reduce many barriers. For instance, studies highlight program costs, ease of administration, multi-cohort vaccination delivery, and increased HPV vaccine program adoption in populations with limited access to healthcare and a high burden of cervical cancer (33).
With growing evidence of the potential efficacy of a one-dose approach, new predictive modeling is underway. Additional simulation models suggest that one-dose vaccination has similar health benefits to a two-dose regimen but also simplifies vaccine delivery, reduces costs, and helps to alleviate vaccine supply constraints (35, 36). Countries that have yet to implement an HPV vaccination program or have low coverage but a high burden of HPV-related diseases may benefit by implementing one-dose vaccination (37). Available resources in LMICs favor a one-dose approach, but data are needed to support adoption (38). Evidence may be sufficient to alter existing guidelines by 2025 (39).
Considering gender-neutral vaccination programs
Eliminating cervical cancer means reducing the incidence to <4/100,000. The current approach, with sustained vaccination for girls only, will change disease rates in 70 years if 100% coverage occurs (40–43). If it is impossible to reach 70% coverage for girls, superior cancer control will need gender-neutral immunization in order to more rapidly impact disease rates (44). Recent modeling assumes HPV vaccine efficacy is >85% and confers lifelong protection. Extending the target-age range of girls and women and focusing on boys is more cost-effective than giving a second dose to girls aged 9–14 when the outcomes are the maximum ICER (incremental cost-effectiveness ratio) and the minimum NNT (number needed to treat). This result applies to India, Vietnam, Uganda, and Nigeria, the countries under study (33).
The epidemiological and economic considerations about vaccinating boys should focus on the benefits in terms of disease reduction, the feasibility and incremental marginal costs of increasing vaccination coverage among girls vs. introducing a gender-neutral program (41, 45). Importantly, gender-neutral HPV vaccination programs will also depend on population acceptability (14, 36, 46, 47) and political viability (47–50).
Discussion
Forward perspective
It is time to reconsider a gendered approach to vaccination to best respond to the WHO's call to eliminate cervical cancer. To date, modeling has primarily been driven by reconciling constraints (vaccine availability and financial barriers) with consideration of cost-effectiveness. With advancing knowledge that potentially reinforces a single-dose approach, the potential to vaccinate more people with current vaccine supplies emerges (i.e., the transition to single dose looks to be promising and is a reasonable expectation to be considered). Other possibilities that may alter vaccine availability include: (1) vaccine cost decline, (2) increased production, and (3) changes in licensing policy. With these considerations, a shift in resource availability may result in opportunities to transition global HPV vaccine programs to alternative approaches. There is a need to continue reworking HPV vaccination models and inform potential approaches through implementation research. Currently, research on implementing a gender-neutral HPV vaccination approach is lacking, and understanding the context in which gender-neutral programs will be successfully adopted is critical.
A gender-neutral HPV vaccination approach will advance the health of both male and female populations. In women, HPV vaccination must include at least one primary HPV screening test in the woman's mid-life. HPV vaccines are incomplete in their genotype prevention, and screening is necessary to reduce the incidence to achieve the WHO elimination goal of <4/100,000. The screening services are likely to be more effective in a population already vaccinated as the underlying prevalence of HPV infection will be lower. Likewise, the treatment services will go to fewer numbers of women who still develop CIN 3 or early cervical cancers.
Knowledge gaps informing a gender neutral approach in LMICs
Adopting a gender-neutral HPV vaccine approach will reduce HPV infections transmitted among the population. We must plan for HPV vaccine uptake, combat misinformation, minimize vaccine-related stigma, and promote gender equity (46). HPV is not a virus that only infects female epithelium; instead, it is a gender-neutral infection. We propose approaching programmatic research through a gender-neutral lens to reduce HPV infections and cancers and promote gender equality (51).
To achieve these goals, we must begin to understand the local community-based customs that will affect the acceptability of gender-neutral vaccination programs in LMICs. Having male and female population endorsement is critical to a gender-neutral approach to HPV vaccination. Once a community-based agreement pushes for gender-neutral vaccination, we must have the data to show the effectiveness of a single HPV vaccine dose in males, as we currently do for females. Designing and supporting variable dose HPV vaccine studies in males is critical for long-term follow-up. There is little literature monitoring male serologic titers and HPV-related outcomes (52).
In addition, implementation research is needed to inform the acceptability, adoption, appropriateness, feasibility, fidelity, implementation cost, penetration, and sustainability of transitioning to a gender neutral approach. There is some recent literature describing the barriers toward HPV vaccinations for boys. However these reports are mostly in high-income countries or upper middle-income countries (53). We are not aware of literature on this topic in the LMIC context. Given the benefit of developing gender neutral HPV vaccination programs in the effort to eliminate cervical cancer, it is imperative that we build knowledge around this topic in order to inform policy-makers and funders in consideration of the possibility for future policy shifts.
Limitations
There are some limitations to the stated argument in favor of advancing research in order to inform the consideration of developing gender neutral HPV vaccination programs. Foremost, there is a noted distinction between the WHO goal of elimination of cervical cancer and individual country-level health ministry considerations regarding research evaluating cost effectiveness of HPV vaccination strategies. It is not always possible to compare all variables across these perspectives. Therefore, these goals may not align in many cases and contextual considerations may weigh certain variables in lieu of others. Secondly, given that resources are currently limited and arguments relative to future availability of the HPV vaccine are, ultimately, conjecture, the current modeling limitations create gaps in our ability to precisely estimate the effects of any potential change in resources. Thirdly, our call to action does not fully consider currently unknown, or unconsidered, repercussions of a significant change in vaccination strategy such as effects on supply chains and distribution channels of the HPV vaccine between and within countries. Our hope is that implementation research would help to shine light on these types of challenges, thus informing future policy-makers at all levels. In addition, it is noted that there is a lack of effective HPV screening methods in men and research exploring male HPV infection is deficient (54). Additional studies assessing the cost-effectiveness of HPV testing in men and modeling studies to assess the effects in females of adding males to existing HPV vaccination programs are needed (55). Lastly, a major unaccounted shift in vaccine technology could also significantly alter these considerations. Ultimately, these limitations may also be concurrently viewed as additional evidence of the need for more research.
Conclusion
HPV and HPV vaccination are sensitive topics and are commonly associated with misinformation, rumors, and stigma (56–58). In order to design more effective policies and programs, a better understanding of the perspectives of clients, clinicians, community leaders, and policy-makers is needed. A clear, multi-level understanding of these stakeholders' views will facilitate the development of target policy and programs aimed at addressing common barriers and optimizing uptake. Given the benefit of developing gender-neutral HPV vaccination programs to eliminate cervical cancer, we must build knowledge around this topic to inform policy-makers and funders for future policy shifts.
Author contributions
JD, CP, HH, and DH contributed to the conceptualization, analysis, interpretation and writing of the paper. All authors contributed to the article and approved the submitted version.
Funding
This research was partially supported by a generous donation from Dr. Fran Jaeger to the University of Illinois Chicago School of Public Health Global Health Program.
Conflict of interest
The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
Publisher's note
All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.
Abbreviations
HPV, human papillomavirus; WHO, World Health Organization; LMIC, low- and lower-middle-income country.
References
1. Kombe AJ, Kombe AJK, Li B, Zahid A, Mengist HM, Bounda G-A, et al. Epidemiology and burden of human papillomavirus and related diseases, molecular pathogenesis, and vaccine evaluation. Front Public Health. (2021) 8:552028. doi: 10.3389/fpubh.2020.552028
2. Castellsagué X, Schneider A, Kaufmann AM, Bosch FX. HPV vaccination against cervical cancer in women above 25 years of age: key considerations and current perspectives. Gynecol Oncol. (2009) 115:S15–23. doi: 10.1016/j.ygyno.2009.09.021
3. Chesson HW, Dunne EF, Hariri S, Markowitz LE. The estimated lifetime probability of acquiring human papillomavirus in the United States. Sex Transm Dis. (2014) 41:660–4. doi: 10.1097/OLQ.0000000000000193
4. Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, Jemal A. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. (2018) 68:394–424. doi: 10.3322/caac.21492
5. Cervix uteri cancer fact sheet; 2020. International Agency for Research on Cancer, The Global Cancer Observatory. (2021). Available online at: https://gco.iarc.fr/today/data/factsheets/cancers/23-Cervix-uteri-fact-sheet.pdf (accessed January 31, 2023).
6. World Health Organization Others. Projections of Mortality and Causes of Death, 2015 and 2030. Geneva: The World Health Organization (2015).
7. The Global Cancer Observatory: Cancer Tomorrow. Available online at: https://gco.iarc.fr/tomorrow/en/dataviz/isotype?cancers=23&single_unit=50000 (accessed August 2, 2022).
8. Forman D, De Martel C, Lacey CJ, Soerjomataram I, Lortet-Tieulent J, Bruni L, et al. Global burden of human papillomavirus and related diseases. Vaccine. (2012) 30:F12–23. doi: 10.1016/j.vaccine.2012.07.055
9. Khan MJ, Castle PE, Lorincz AT, Wacholder S, Sherman M, Scott DR, et al. The elevated 10-year risk of cervical precancer and cancer in women with human papillomavirus (HPV) type 16 or 18 and the possible utility of type-specific HPV testing in clinical practice. J Natl Cancer Inst. (2005) 97:1072–9. doi: 10.1093/jnci/dji187
10. Global Strategy to Accelerate the Elimination of Cervical Cancer as a Public Health Problem. Geneva: World Health Organization. (2020). Available online at: https://apps.who.int/iris/bitstream/handle/10665/336583/9789240014107-eng.pdf (accessed January 31, 2023).
11. Bosch FX, Burchell AN, Schiffman M, Giuliano AR, de Sanjose S, Bruni L, et al. Epidemiology and natural history of human papillomavirus infections and type-specific implications in cervical neoplasia. Vaccine. (2008) 26:K1–16. doi: 10.1016/j.vaccine.2008.05.064
12. Hull R, Mbele M, Makhafola T, Hicks C, Wang S-M, Reis RM, et al. Cervical cancer in low and middle-income countries. Oncol Lett. (2020) 20:2058–74. doi: 10.3892/ol.2020.11754
13. Global HPV Vaccine Introduction Overview. PATH. (2022). Available online at: https://www.path.org/resources/global-hpv-vaccine-introduction-overview/ (accessed July 21, 2022).
14. Dorji T, Nopsopon T, Tamang ST, Pongpirul K. Human papillomavirus vaccination uptake in low-and middle-income countries: a meta-analysis. EClinicalMedicine. (2021) 34:100836. doi: 10.1016/j.eclinm.2021.100836
15. Delany-Moretlwe S, Kelley KF, James S, Scorgie F, Subedar H, Dlamini NR, et al. Human papillomavirus vaccine introduction in South Africa: implementation lessons from an evaluation of the national school-based vaccination campaign. Glob Health Sci Pract. (2018) 6:425–38. doi: 10.9745/GHSP-D-18-00090
16. Brenzel L. What have we learned on costs and financing of routine immunization from the comprehensive multi-year plans in GAVI eligible countries? Vaccine. (2015) 33:A93–8. doi: 10.1016/j.vaccine.2014.12.076
17. Soi C, Babigumira JB, Chilundo B, Muchanga V, Matsinhe L, Gimbel S, et al. Implementation strategy and cost of Mozambique's HPV vaccine demonstration project. BMC Public Health. (2019) 19:1406. doi: 10.1186/s12889-019-7793-y
18. World Health Organization Others. Guide to Introducing HPV Vaccine into National Immunization Programmes. Geneva: World Health Organization (2016). Available online at: https://apps.who.int/iris/bitstream/handle/10665/253123/9789241549769-eng.pdf
19. Bruni L, Saura-Lázaro A, Montoliu A, Brotons M, Alemany L, Diallo MS, et al. HPV vaccination introduction worldwide and WHO and UNICEF estimates of national HPV immunization coverage 2010–2019. Prev Med. (2021) 144:106399. doi: 10.1016/j.ypmed.2020.106399
20. Brisson M, Jit M, Boily M-C, Laprise J, Martin D, Drolet M, Alary M, Benard E. Modelling estimates of the incremental effectiveness & cost-effectiveness of HPV vaccination. World Health Organization Strategic Advisory Group of Experts (SAGE) on immunization meeting. Geneva: WHO (2016). Available online at: https://terrance.who.int/mediacentre/data/sage/SAGE_Docs_Ppt_Oct2016/10_session_HPV/Oct2016_session10_HPV_CEA-ICER.pdf (accessed January 31, 2023).
21. Ng SS, Hutubessy R, Chaiyakunapruk N. Systematic review of cost-effectiveness studies of human papillomavirus (HPV) vaccination: 9-valent vaccine, gender-neutral and multiple age cohort vaccination. Vaccine. (2018) 36:2529–44. doi: 10.1016/j.vaccine.2018.03.024
22. World Health Organization. Electronic address: sageexecsec@who.int. Human papillomavirus vaccines: WHO position paper, May 2017-recommendations. Vaccine. (2017) 35:5753–5755. doi: 10.1016/j.vaccine.2017.05.069
23. Global HPV Vaccine Introduction Overview: Projected Current National Introductions Demonstration/Pilot Projects Gender-neutral Vaccination Programs Global HPV Vaccine Introduction Maps (2006–2022). PATH. (2021). Available online at: https://path.azureedge.net/media/documents/Global_Vaccine_Intro_Overview_Slides_Final_PATHwebsite_2021AUG17_fx7PZjH.pdf (accessed January 31, 2023).
24. Dorji T, Tshomo U, Gyamtsho S, Tamang ST, Wangmo S, Pongpirul K. Gender-neutral HPV elimination, cervical cancer screening, and treatment: experience from Bhutan. Int J Gynaecol Obstet. (2021) 156:425–9. doi: 10.1002/ijgo.13728
25. Daley EM, Vamos CA, Thompson EL, Zimet GD, Rosberger Z, Merrell L, et al. The feminization of HPV: how science, politics, economics and gender norms shaped US HPV vaccine implementation. Papillomavirus Res. (2017) 3:142–8. doi: 10.1016/j.pvr.2017.04.004
26. Qendri V, Bogaards JA, Berkhof J. Who will benefit from expanding HPV vaccination programs to boys? JNCI Cancer Spectr. (2018) 2:ky076. doi: 10.1093/jncics/pky076
27. Basu P, Malvi SG, Joshi S, Bhatla N, Muwonge R, Lucas E, et al. Vaccine efficacy against persistent human papillomavirus (HPV) 16/18 infection at 10 years after one, two, and three doses of quadrivalent HPV vaccine in girls in India: a multicentre, prospective, cohort study. Lancet Oncol. (2021) 22:1518–29. doi: 10.1016/S1470-2045(21)00453-8
28. Kreimer AR, Struyf F, Del Rosario-Raymundo MR, Hildesheim A, Skinner SR, Wacholder S, et al. Efficacy of fewer than three doses of an HPV-16/18 AS04-adjuvanted vaccine: combined analysis of data from the Costa Rica Vaccine and PATRICIA Trials. Lancet Oncol. (2015) 16:775–86. doi: 10.1016/S1470-2045(15)00047-9
29. Sankaranarayanan R, Joshi S, Muwonge R, Esmy PO, Basu P, Prabhu P, et al. Can a single dose of human papillomavirus (HPV) vaccine prevent cervical cancer? Early findings from an Indian study. Vaccine. (2018) 36:4783–91. doi: 10.1016/j.vaccine.2018.02.087
30. Safaeian M, Porras C, Pan Y, Kreimer A, Schiller JT, Gonzalez P, et al. Durable antibody responses following one dose of the bivalent human papillomavirus L1 virus-like particle vaccine in the Costa Rica Vaccine Trial. Cancer Prev Res. (2013) 6:1242–50. doi: 10.1158/1940-6207.CAPR-13-0203
31. Safaeian M, Sampson JN, Pan Y, Porras C, Kemp TJ, Herrero R, et al. Durability of protection afforded by fewer doses of the HPV16/18 vaccine: the CVT Trial. J Natl Cancer Inst. (2018) 110:205–12. doi: 10.1093/jnci/djx158
32. Sankaranarayanan R, Prabhu PR, Pawlita M, Gheit T, Bhatla N, Muwonge R, et al. Immunogenicity and HPV infection after one, two, and three doses of quadrivalent HPV vaccine in girls in India: a multicentre prospective cohort study. Lancet Oncol. (2016) 17:67–77. doi: 10.1016/S1470-2045(15)00414-3
33. Drolet M, Laprise J-F, Martin D, Jit M, Bénard É, Gingras G, et al. Optimal human papillomavirus vaccination strategies to prevent cervical cancer in low-income and middle-income countries in the context of limited resources: a mathematical modelling analysis. Lancet Infect Dis. (2021) 21:1598–610. doi: 10.1016/S1473-3099(20)30860-4
34. Highlights from the Meeting of the Strategic Advisory Group of Experts (SAGE) on Immunization 4-7 April 2022. Geneva: World Health Organization. (2022) Available online at: https://cdn.who.int/media/docs/default-source/reproductive-health/sage_april2022meetinghighlights_11apr2022_final.pdf?sfvrsn=21bcfb4f_3 (accessed January 31, 2023).
35. Prem K, Choi YH, Bénard É, Burger EA, Hadley L, Laprise J-F, et al. Global impact and cost-effectiveness of one-dose versus two-dose human papillomavirus vaccination schedules: A comparative modelling analysis. medRxiv [Preprint]. (2021). doi: 10.2139/ssrn.3779876
36. Tsu VD, LaMontagne DS, Atuhebwe P, Bloem PN, Ndiaye C. National implementation of HPV vaccination programs in low-resource countries: lessons, challenges, and future prospects. Prev Med. (2021) 144:106335. doi: 10.1016/j.ypmed.2020.106335
37. Gilca V, Salmerón-Castro J, Sauvageau C, Ogilvie G, Landry M, Naus M, et al. Early use of the HPV 2-dose vaccination schedule: leveraging evidence to support policy for accelerated impact. Vaccine. (2018) 36:4800–5. doi: 10.1016/j.vaccine.2018.02.004
38. Burger EA, Campos NG, Sy S, Regan C, Kim JJ. Health and economic benefits of single-dose HPV vaccination in a Gavi-eligible country. Vaccine. (2018) 36:4823–9. doi: 10.1016/j.vaccine.2018.04.061
39. Single-Dose HPV Vaccine Evaluation Consortium. A General Summary of Current Published Evidence for Single-dose HPV Vaccination. (2019). Available online at: https://www.path.org/programs/center-for-vaccine-innovation-and-access/single-dose-hpv-vaccine-evaluation-consortium/ (accessed January 31, 2023).
40. Lehtinen M, Baussano I, Paavonen J, Vänskä S, Dillner J. Eradication of human papillomavirus and elimination of HPV-related diseases - scientific basis for global public health policies. Expert Rev Vaccines. (2019) 18:153–60. doi: 10.1080/14760584.2019.1568876
41. Brisson M, Bénard É, Drolet M, Bogaards JA, Baussano I, Vänskä S, et al. Population-level impact, herd immunity, and elimination after human papillomavirus vaccination: a systematic review and meta-analysis of predictions from transmission-dynamic models. Lancet Public Health. (2016) 1:e8–17. doi: 10.1016/S2468-2667(16)30001-9
42. Baussano I, Lazzarato F, Ronco G, Lehtinen M, Dillner J, Franceschi S. Different challenges in eliminating HPV16 compared to other types: a modeling study. J Infect Dis. (2017) 216:336–44. doi: 10.1093/infdis/jix299
43. Elfström KM, Lazzarato F, Franceschi S, Dillner J, Baussano I. Human papillomavirus vaccination of boys and extended catch-up vaccination: effects on the resilience of programs. J Infect Dis. (2016) 213:199–205. doi: 10.1093/infdis/jiv368
44. World Health Organization Others. 2018 Assessment Report of the Global Vaccine Action Plan: Strategic Advisory Group of Experts on Immunization. Geneva: World Health Organization (2018). Available online at: https://apps.who.int/iris/handle/10665/276967 (accessed January 31, 2023).
45. Ryser MD, McGoff K, Herzog DP, Sivakoff DJ, Myers ER. Impact of coverage-dependent marginal costs on optimal HPV vaccination strategies. Epidemics. (2015) 11:32–47. doi: 10.1016/j.epidem.2015.01.003
46. Deignan C, Swartz A, Cooper S, Colvin CJ. Stakeholders' understandings of human papillomavirus (HPV) vaccination in Sub-Saharan Africa: a rapid qualitative systematic review. Vaccines. (2021) 9:496. doi: 10.3390/vaccines9050496
47. Steben M, Jeronimo J, Wittet S, Lamontagne DS, Ogilvie G, Jensen C, et al. Upgrading public health programs for human papillomavirus prevention and control is possible in low- and middle-income countries. Vaccine. (2012) 30:F183–91. doi: 10.1016/j.vaccine.2012.06.031
48. Giuliano AR, Salmon D. The case for a gender-neutral (universal) human papillomavirus vaccination policy in the United States: point. Cancer Epidemiol Biomarkers Prev. (2008) 17:805–8. doi: 10.1158/1055-9965.EPI-07-0741
49. Zimet GD, Meyerson BE, Dutta T, Forster A, Corcoran B, Hanley S. Political and public responses to human papillomavirus vaccination. Hum Papillomavirus. (2020) 363–377. doi: 10.1016/B978-0-12-814457-2.00022-2
50. Duncan J, Harris M, Skyers N, Bailey A, Figueroa JP. A call for low- and middle-income countries to commit to the elimination of cervical cancer. Lancet Reg Health Am. (2021) 2:100036. doi: 10.1016/j.lana.2021.100036
51. Crosignani P, De Stefani A, Fara GM, Isidori AM, Lenzi A, Liverani CA, et al. Towards the eradication of HPV infection through universal specific vaccination. BMC Public Health. (2013) 13:642. doi: 10.1186/1471-2458-13-642
52. Foerster V, Khangura S, Severn M. HPV Vaccination in Men: A Review of Clinical Effectiveness, Cost-Effectiveness, and Guidelines. Ottawa, ON: Canadian Agency for Drugs and Technologies in Health (2017).
53. Grandahl M, Nevéus T. Barriers towards HPV vaccinations for boys and young men: a narrative review. Viruses. (2021) 13:1644. doi: 10.3390/v13081644
54. Preston SM, Darrow WW. Are Men being left behind (or catching up)? Differences in HPV awareness, knowledge, and attitudes between diverse college men and women. Am J Mens Health. (2019) 13:1557988319883776. doi: 10.1177/1557988319883776
55. Harder T, Wichmann O, Klug SJ, van der Sande MAB, Wiese-Posselt M. Efficacy, effectiveness and safety of vaccination against human papillomavirus in males: a systematic review. BMC Med. (2018) 16:110. doi: 10.1186/s12916-018-1098-3
56. Ginjupalli R, Mundaden R, Choi Y, Herfel E, Oketch SY, Watt MH, et al. Developing a framework to describe stigma related to cervical cancer and HPV in western Kenya. BMC Womens Health. (2022) 22:39. doi: 10.1186/s12905-022-01619-y
57. Peterson CE, Silva A, Goben AH, Ongtengco NP, Hu EZ, Khanna D, et al. Stigma and cervical cancer prevention: a scoping review of the US literature. Prev Med. (2021) 153:106849. doi: 10.1016/j.ypmed.2021.106849
Keywords: HPV, cervical cancer, cancer prevention, policy, vaccine program
Citation: Dykens JA, Peterson CE, Holt HK and Harper DM (2023) Gender neutral HPV vaccination programs: Reconsidering policies to expand cancer prevention globally. Front. Public Health 11:1067299. doi: 10.3389/fpubh.2023.1067299
Received: 11 October 2022; Accepted: 23 January 2023;
Published: 21 February 2023.
Edited by:
Ronell Bologna-Molina, Universidad de la República, UruguayReviewed by:
Lihui Wei, Peking University People's Hospital, ChinaRogelio González-González, Juárez University of the State of Durango, Mexico
Copyright © 2023 Dykens, Peterson, Holt and Harper. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
*Correspondence: J. Andrew Dykens, 
jdykens@uic.edu