Ignored and undervalued in public health: a systematic review of health state utility values associated with syphilis infection.

BACKGROUND: Syphilis is a sexually transmitted infection causing significant global morbidity and mortality. To inform policymaking and economic evaluation studies for syphilis, we summarised utility and disability weights for health states associated with syphilis. METHODS: We conducted a systematic review, searching six databases for economic evaluations and primary valuation studies related to syphilis from January 2000 to February 2022. We extracted health state utility values or disability weights, including identification of how these were derived. The study was registered in the international prospective register of systematic reviews (PROSPERO, CRD42021230035). FINDINGS: Of 3401 studies screened, 22 economic evaluations, two primary studies providing condition-specific measures, and 13 burden of disease studies were included. Fifteen economic evaluations reported outcomes as disability-adjusted life years (DALYs) and seven reported quality-adjusted life years (QALYs). Fourteen of 15 economic evaluations that used DALYS based their values on the original Global Burden of Disease (GBD) study from 1990 (published in 1996). For the seven QALY-related economic evaluations, the methodology varied between studies, with some studies using assumptions and others creating utility weights or converting them from disability weights. INTERPRETATION: We found a limited evidence base for the valuation of health states for syphilis, a lack of transparency for the development of existing health state utility values, and inconsistencies in the application of these values to estimate DALYs and QALYs. Further research is required to expand the evidence base so that policymakers can access accurate and well-informed economic evaluations to allocate resources to address syphilis and implement syphilis programs that are cost-effective.

Missed opportunities for HIV testing among those who accessed sexually transmitted infection (STI) services, tested for STIs and diagnosed with STIs: a systematic review and meta-analysis.

INTRODUCTION: Of 37.7 million people living with HIV in 2020, 6.1 million still do not know their HIV status. We synthesize evidence on concurrent HIV testing among people who tested for other sexually transmitted infections (STIs). METHODS: We conducted a systematic review using five databases, HIV conferences and clinical trial registries. We included publications between 2010 and May 2021 that reported primary data on concurrent HIV/STI testing. We conducted a random-effects meta-analysis and meta-regression of the pooled proportion for concurrent HIV/STI testing. RESULTS: We identified 96 eligible studies. Among those, 49 studies had relevant data for a meta-analysis. The remaining studies provided data on the acceptability, feasibility, barriers, facilitators, economic evaluation and social harms of concurrent HIV/STI testing. The pooled proportion of people tested for HIV among those attending an STI service (n = 18 studies) was 71.0% (95% confidence intervals: 61.0-80.1, I2 = 99.9%), people tested for HIV among those who were tested for STIs (n = 15) was 61.3% (53.9-68.4, I2 = 99.9%), people tested for HIV among those who were diagnosed with an STI (n = 13) was 35.3% (27.1-43.9, I2 = 99.9%) and people tested for HIV among those presenting with STI symptoms (n = 3) was 27.1% (20.5-34.3, I2 = 92.0%). The meta-regression analysis found that heterogeneity was driven mainly by identity as a sexual and gender minority, the latest year of study, country-income level and region of the world. DISCUSSION: This review found poor concurrent HIV/STI testing among those already diagnosed with an STI (35.3%) or who had symptoms with STIs (27.1%). Additionally, concurrent HIV/STI testing among those tested for STIs varied significantly according to the testing location, country income level and region of the world. A few potential reasons for these observations include differences in national STI-related policies, lack of standard operation procedures, clinician-level factors, poor awareness and adherence to HIV indicator condition-guided HIV testing and stigma associated with HIV compared to other curable STIs. CONCLUSIONS: Not testing for HIV among people using STI services presents a significant missed opportunity, particularly among those diagnosed with an STI. Stronger integration of HIV and STI services is urgently needed to improve prevention, early diagnosis and linkage to care services.

Understanding the public health value and defining preferred product characteristics for therapeutic human papillomavirus (HPV) vaccines: World Health Organization consultations, October 2021-March 2022.

The World Health Organization (WHO) global strategy to eliminate cervical cancer (CxCa) could result in >62 million lives saved by 2120 if strategy targets are reached and maintained: 90% of adolescent girls receiving prophylactic human papillomavirus (HPV) vaccine, 70% of women receiving twice-lifetime cervical cancer screening, and 90% of cervical pre-cancer lesions and invasive CxCa treated. However, the cost and complexity of CxCa screening and treatment approaches has hampered scale-up, particularly in low- and middle-income countries (LMICs), and new approaches are needed. Therapeutic HPV vaccines (TxV), which could clear persistent high-risk HPV infection and/or cause regression of pre-cancerous lesions, are in early clinical development and might offer one such approach. During October 2021 to March 2022, WHO, in collaboration with the Bill and Melinda Gates Foundation, convened a series of global expert consultations to lay the groundwork for understanding the potential value of TxV in the context of current CxCa prevention efforts and for defining WHO preferred product characteristics (PPCs) for TxV. WHO PPCs describe preferences for vaccine attributes that would help optimize vaccine value and use in meeting the global public health need. This paper reports on the main discussion points and findings from the expert consultations. Experts identified several ways in which TxV might address challenges in current CxCa prevention programmes, but emphasized that the potential value of TxV will depend on their degree of efficacy and how quickly they can be developed and implemented relative to ongoing scale-up of existing interventions. Consultation participants also discussed potential use-cases for TxV, important PPC considerations (e.g., vaccine indications, target populations, and delivery strategies), and critical modelling needs for predicting TxV impact and cost-effectiveness.

Assessment of country implementation of the WHO global health sector strategy on sexually transmitted infections (2016-2021).

BACKGROUND: In 2016, WHO launched the Global Health Sector Strategy on STIs, 2016-2021 (GHSS) to provide guidance and benchmarks for country achievement by 2020 and four global targets for achievement by 2030. METHODS: A country survey jointly developed by experienced technical personnel at WHO Headquarters (HQ) and WHO regional offices was reviewed and distributed by WHO regional advisors to 194 WHO Member States in September-March 2020. The survey sought to assess implementation and prioritization of STI policy, surveillance, service delivery, commodity availability, and surveillance based on targets of the GHSS. RESULTS: A majority (58%, 112/194) of countries returned a completed survey reflecting current (2019) STI activities. The regions with the highest survey completion rates were South-East Asia Region (91%, 10/11), Region of the Americas (71%, 25/35) and Western Pacific Region (67%, 18/27). Having a national STI strategy was reported by 64% (72/112) and performing STI surveillance activities by 88% (97/110) of reporting countries. Availability of STI services within primary health clinics was reported by 88% of countries (99/112); within HIV clinics by 92% (103/112), and within reproductive health services by 85% (95/112). Existence of a national strategy to eliminate mother-to-child transmission of HIV and syphilis (EMTCT) was reported by 70% of countries (78/112). Antimicrobial resistance (AMR) monitoring for gonococcal infection (gonorrhoea) was reported by 64% (57/89) of reporting countries with this laboratory capacity. Inclusion of HPV vaccine for young women in the national immunization schedule was reported by 59% (65/110) and availability of cervical cancer screening was reported by 91% (95/104). Stockouts of STI medicines, primarily benzathine penicillin, within the prior four years were reported by 34% (37/110) of countries. CONCLUSIONS: Mechanisms to support improvements to STI service delivery through national-level policy, commitment, programming and surveillance are needed to operationalize, accelerate and monitor progress towards achievement of the 2030 global STI strategy targets.

Health-related quality of life in individuals with genital herpes: a systematic review.

BACKGROUND: There is a significant global burden of herpes simplex virus (HSV) related genital ulcer disease yet little is known about its impact on quality of life. This systematic review aimed to identify studies that quantitatively evaluated the effect of genital herpes on various aspects of health-related quality of life. METHODS: Six databases were searched (MEDLINE, EMBASE, NHS Economic Evaluation Database, Health Technology Assessment, Database of Abstracts of Reviews of Effects, Web of Science Core Collection) for primary quality of life and economic evaluations of genital herpes from January 1, 2000 to January 7, 2021. Qualitative studies or those without primary data were excluded. Two authors independently extracted data from the publications. The study's registration number with PROSPERO was CRD42021239410. FINDINGS: We identified 26 relevant publications: 19 presented primary quality of life data, and seven were economic evaluations. The primary studies presented a range of condition-specific tools for describing the quality of life in individuals with genital herpes, but only one study used a direct valuation that could be used to generate utility weights. All economic evaluations of HSV infection were from high-income country settings. Most (6 of 7) focused on neonatal HSV infection with utilities adopted from studies prior to 2000. INTERPRETATION: The extant literature on genital herpes-related quality of life is limited and requires updating. We recommend future studies be conducted in geographic- and population- diverse settings, and use preference-based condition-specific or generic-instruments to better inform economic modelling.

Healthcare resource utilisation pattern and costs associated with herpes simplex virus diagnosis and management: a systematic review.

OBJECTIVES: Little is known about the economic burden of herpes simplex virus (HSV) across countries. This article aims to summarise existing evidence on estimates of costs and healthcare resource utilisation associated with genital and neonatal HSV infection. DESIGN: Systematic literature review. DATA SOURCES: Seven databases were searched from inception to 31 August 2020. A focused search was performed to supplement the results. ELIGIBILITY CRITERIA: Studies which reported either healthcare resource utilisation or costs associated with HSV-related healthcare, including screening, diagnosis and treatment of genital HSV infection and neonatal herpes prevention and treatment. DATA EXTRACTION AND SYNTHESIS: Two independent reviewers extracted data and assessed the risk of bias using the Larg and Moss's checklist. All data were summarised narratively. RESULTS: Out of 11 443 articles, 38 were included. Most studies (35/38, 94.6%) were conducted in high-income countries, primarily the United States, and were more often related to the prevention or management of neonatal herpes (n=21) than HSV genital ulcer disease (n=17). Most analyses were conducted before 2010. There was substantial heterogeneity in the reporting of HSV-related healthcare resource utilisation, with 74%-93% individuals who sought care for HSV, 11.6%-68.4% individuals who received care, while neonates with herpes required a median of 6-34 hospitalisation days. The costs reported were similarly heterogeneous, with wide variation in methodology, assumptions and outcome measures between studies. Cost for screening ranged from US$7-100, treatment ranged from US$0.53-35 for an episodic therapy, US$240-2580 yearly for suppressive therapy, while hospitalisation for neonatal care ranged from US$5321-32 683. CONCLUSIONS: A paucity of evidence exists on healthcare resource utilisation and costs associated with HSV infection, especially among low-income and middle-income countries. Future research is needed on costs and healthcare utilisation patterns to improve overall understanding of the global economic burden of HSV.

Estimates of the global burden of cervical cancer associated with HIV.

BACKGROUND: HIV enhances human papillomavirus (HPV)-induced carcinogenesis. However, the contribution of HIV to cervical cancer burden at a population level has not been quantified. We aimed to investigate cervical cancer risk among women living with HIV and to estimate the global cervical cancer burden associated with HIV. METHODS: We did a systematic literature search and meta-analysis of five databases (PubMed, Embase, Global Health [CABI.org], Web of Science, and Global Index Medicus) to identify studies analysing the association between HIV infection and cervical cancer. We estimated the pooled risk of cervical cancer among women living with HIV across four continents (Africa, Asia, Europe, and North America). The risk ratio (RR) was combined with country-specific UNAIDS estimates of HIV prevalence and GLOBOCAN 2018 estimates of cervical cancer to calculate the proportion of women living with HIV among women with cervical cancer and population attributable fractions and age-standardised incidence rates (ASIRs) of HIV-attributable cervical cancer. FINDINGS: 24 studies met our inclusion criteria, which included 236 127 women living with HIV. The pooled risk of cervical cancer was increased in women living with HIV (RR 6·07, 95% CI 4·40-8·37). Globally, 5·8% (95% CI 4·6-7·3) of new cervical cancer cases in 2018 (33 000 new cases, 95% CI 26 000-42 000) were diagnosed in women living with HIV and 4·9% (95% CI 3·6-6·4) were attributable to HIV infection (28 000 new cases, 20 000-36 000). The most affected regions were southern Africa and eastern Africa. In southern Africa, 63·8% (95% CI 58·9-68·1) of women with cervical cancer (9200 new cases, 95% CI 8500-9800) were living with HIV, as were 27·4% (23·7-31·7) of women in eastern Africa (14 000 new cases, 12 000-17 000). ASIRs of HIV-attributable cervical cancer were more than 20 per 100 000 in six countries, all in southern Africa and eastern Africa. INTERPRETATION: Women living with HIV have a significantly increased risk of cervical cancer. HPV vaccination and cervical cancer screening for women living with HIV are especially important for countries in southern Africa and eastern Africa, where a substantial HIV-attributable cervical cancer burden has added to the existing cervical cancer burden. FUNDING: WHO, US Agency for International Development, and US President's Emergency Plan for AIDS Relief.

Gonococcal vaccines: Public health value and preferred product characteristics; report of a WHO global stakeholder consultation, January 2019.

Renewed interest in developing vaccines against Neisseria gonorrhoeae has been sparked by the increasing threat of gonococcal antimicrobial resistance (AMR) and growing optimism that gonococcal vaccines are biologically feasible. Evidence suggests serogroup B Neisseria meningitidis vaccines might provide some cross-protection against N. gonorrhoeae, and new gonococcal vaccine candidates based on several approaches are currently in preclinical development. To further stimulate investment and accelerate development of gonococcal vaccines, greater understanding is needed regarding the overall value that gonococcal vaccines might have in addressing public health and societal goals in low-, middle-, and high-income country contexts and how future gonococcal vaccines might be accepted and used, if available. In January 2019, the World Health Organization (WHO) convened a multidisciplinary international group of experts to lay the groundwork for understanding the potential health, economic, and societal value of gonococcal vaccines and their likely acceptance and use, and for developing gonococcal vaccine preferred product characteristics (PPCs). WHO PPCs describe preferences for vaccine attributes that would help optimize vaccine value and use in meeting the global public health need. This paper describes the main discussion points and conclusions from the January 2019 meeting of experts. Participants emphasized the need for vaccines to control N. gonorrhoeae infections with the ultimate goals of preventing adverse sexual and reproductive health outcomes (e.g., infertility) and reducing the impact of gonococcal AMR. Meeting participants also discussed important PPC considerations (e.g., vaccine indications, target populations, and potential immunization strategies) and highlighted crucial research and data needs for guiding the value assessment and PPCs for gonococcal vaccines and advancing gonococcal vaccine development.

Prevalence of sexually transmitted infections and bacterial vaginosis among women in sub-Saharan Africa: An individual participant data meta-analysis of 18 HIV prevention studies.

BACKGROUND: Estimates of sexually transmitted infection (STI) prevalence are essential for efforts to prevent and control STIs. Few large STI prevalence studies exist, especially for low- and middle-income countries (LMICs). Our primary objective was to estimate the prevalence of chlamydia, gonorrhea, trichomoniasis, syphilis, herpes simplex virus type 2 (HSV-2), and bacterial vaginosis (BV) among women in sub-Saharan Africa by age, region, and population type. METHODS AND FINDINGS: We analyzed individual-level data from 18 HIV prevention studies (cohort studies and randomized controlled trials; conducted during 1993-2011), representing >37,000 women, that tested participants for ≥1 selected STIs or BV at baseline. We used a 2-stage meta-analysis to combine data. After calculating the proportion of participants with each infection and standard error by study, we used a random-effects model to obtain a summary mean prevalence of each infection and 95% confidence interval (CI) across ages, regions, and population types. Despite substantial study heterogeneity for some STIs/populations, several patterns emerged. Across the three primary region/population groups (South Africa community-based, Southern/Eastern Africa community-based, and Eastern Africa higher-risk), prevalence was higher among 15-24-year-old than 25-49-year-old women for all STIs except HSV-2. In general, higher-risk populations had greater prevalence of gonorrhea and syphilis than clinic/community-based populations. For chlamydia, prevalence among 15-24-year-olds was 10.3% (95% CI: 7.4%, 14.1%; I2 = 75.7%) among women specifically recruited from higher-risk settings for HIV in Eastern Africa and was 15.1% (95% CI: 12.7%, 17.8%; I2 = 82.3%) in South African clinic/community-based populations. Among clinic/community-based populations, prevalence was generally greater in South Africa than in Southern/Eastern Africa for most STIs; for gonorrhea, prevalence among 15-24-year-olds was 4.6% (95% CI: 3.3%, 6.4%; I2 = 82.8%) in South Africa and was 1.7% (95% CI: 1.2%, 2.6%; I2 = 55.2%) in Southern/Eastern Africa. Across the three primary region/population groups, HSV-2 and BV prevalence was high among 25-49-year-olds (ranging from 70% to 83% and 33% to 44%, respectively). The main study limitation is that the data are not from random samples of the target populations. CONCLUSIONS: Combining data from 18 HIV prevention studies, our findings highlight important features of STI/BV epidemiology among sub-Saharan African women. This methodology can be used where routine STI surveillance is limited and offers a new approach to obtaining critical information on STI and BV prevalence in LMICs.

Toward global prevention of sexually transmitted infections (STIs): the need for STI vaccines.

An estimated 499 million curable sexually transmitted infections (STIs; gonorrhea, chlamydia, syphilis, and trichomoniasis) occurred globally in 2008. In addition, well over 500 million people are estimated to have a viral STI such as herpes simplex virus type 2 (HSV-2) or human papillomavirus (HPV) at any point in time. STIs result in a large global burden of sexual, reproductive, and maternal-child health consequences, including genital symptoms, pregnancy complications, cancer, infertility, and enhanced HIV transmission, as well as important psychosocial consequences and financial costs. STI control strategies based primarily on behavioral primary prevention and STI case management have had clear successes, but gains have not been universal. Current STI control is hampered or threatened by several behavioral, biological, and implementation challenges, including a large proportion of asymptomatic infections, lack of feasible diagnostic tests globally, antimicrobial resistance, repeat infections, and barriers to intervention access, availability, and scale-up. Vaccines against HPV and hepatitis B virus offer a new paradigm for STI control. Challenges to existing STI prevention efforts provide important reasons for working toward additional STI vaccines. We summarize the global epidemiology of STIs and STI-associated complications, examine challenges to existing STI prevention efforts, and discuss the need for new STI vaccines for future prevention efforts.

Trends in seroprevalence of herpes simplex virus type 2 among non-Hispanic blacks and non-Hispanic whites aged 14 to 49 years--United States, 1988 to 2010.

OBJECTIVES: Genital herpes simplex virus type 2 (HSV-2) is one of the most prevalent sexually transmitted infections in the United States. We sought to assess differences in HSV-2 seroprevalence among non-Hispanic blacks and non-Hispanic whites and describe trends over time from 1988 to 2010. METHODS: Data from National Health and Nutrition Examination Surveys (NHANES) were used to determine national HSV-2 seroprevalence estimates from National Health and Nutrition Examination Surveys 1988 to 1994, 1999 to 2002, 2003 to 2006, and 2007 to 2010. Persons aged 14 to 49 years were included in the analyses. Race/Ethnicity was defined by self-report as non-Hispanic white or non-Hispanic black. Purified glycoprotein specific for HSV-2 was used to detect type-specific antibodies using an immunodot assay. The same assay was used in all surveys. History of diagnosed genital herpes was self-reported. RESULTS: Overall, HSV-2 seroprevalence decreased in the United States between 1988 to 1994 and 2007 to 2010, from 21.2% to 15.5%. Among non-Hispanic white females, HSV-2 seroprevalence decreased from 19.5% (1988-1994) to 15.3% (2007-2010; P < 0.001); HSV-2 seroprevalence remained stable among non-Hispanic black females, 52.5% (1988-1994) to 49.9% (2007-2010; P = 0.1). The female black/white prevalence ratio was 2.7 (95% confidence interval [CI], 2.4-3.0) in 1988 to 1994 increasing to 3.3 (95% CI, 2.9-3.7) in 2007 to 2010 (P = 0.01). Among males, the black/white prevalence ratio was 2.4 (95% CI, 1.9-2.9) in 1988 to 1994 increasing to 4.4 (95% CI, 3.3-5.8) in 2007 to 2010 (P = 0.001). The overall percentage of HSV-2-seropositive survey participants who reported never being told by a doctor or health care professional that they had genital herpes did not change significantly between 1988 to 1994 and 2007 to 2010 and remained high (90.7% and 87.4%, respectively). CONCLUSIONS: Although HSV-2 seroprevalence decreased overall, the decrease was most marked among non-Hispanic whites, and racial disparities significantly increased over time. These persistent disparities demonstrate the need for innovative prevention strategies among this at-risk population.

Screening and treating Chlamydia trachomatis genital infection to prevent pelvic inflammatory disease: interpretation of findings from randomized controlled trials.

We critically reviewed randomized controlled trials evaluating chlamydia screening to prevent pelvic inflammatory disease (PID) and explored factors affecting interpretation and translation of trial data into public health prevention. Taken together, data from these trials offer evidence that chlamydia screening and treatment is an important and useful intervention to reduce the risk of PID among young women. However, the magnitude of benefit to be expected from screening may have been overestimated based on the earliest trials. It is likely that chlamydia screening programs have contributed to declines in PID incidence through shortening prevalent infections, although the magnitude of their contribution remains unclear. Program factors such as screening coverage as well as natural history factors such as risk of PID after repeat chlamydia infection can be important in determining the impact of chlamydia screening on PID incidence in a population. Uptake of chlamydia screening is currently suboptimal, and expansion of screening among young, sexually active women remains a priority. To reduce transmission and repeat infections, implementation of efficient strategies to treat partners of infected women is also essential. Results of ongoing randomized evaluations of the effect of screening on community-wide chlamydia prevalence and PID will also be valuable.

Provider perceptions of barriers and facilitators of HPV vaccination in a high-risk community.

BACKGROUND: Maximizing HPV vaccine uptake among those at highest risk for cervical cancer is critical. We explored healthcare provider perspectives on factors influencing HPV vaccination among adolescent girls in a community with high cervical cancer rates. METHODS: From March to May 2009, we conducted in-depth interviews with 21 medical staff providing care to adolescent girls at two clinics in Los Angeles, CA, serving a predominantly Hispanic population with high cervical cancer rates. Interviews were recorded and transcribed data were reviewed for coding and thematic content related to potential barriers and facilitators of HPV vaccination. RESULTS: Providers and medical staff overwhelmingly focused on parental beliefs as barriers to HPV vaccination. Perceived parental misconceptions acting as barriers included the belief that adolescents do not need vaccinations and that no-cost vaccine programs like Vaccines for Children are only available for younger children. Perceived parental concerns that the vaccine will promote sexual activity were prevalent, which prompted providers to frame HPV vaccine as a "routine" vaccine. However, the medical staff felt mothers with a friend or relative supportive of HPV vaccination were more likely to request the vaccine. The staff also noted that for Hispanic parents the "preferred" source of information is peers; if the "right people" in the community were supportive of HPV vaccine, parents were more willing to vaccinate. Other barriers included lack of immunization records among immigrant parents and a difficult-to-reach, mobile clientele. CONCLUSIONS: Providers noted a number of barriers to HPV vaccination, including some perceived parental misconceptions that could be addressed with education about the need for adolescent vaccines and available free vaccine programs. Because community support appears particularly important to Hispanic parents, the use of promotoras - peer liaisons between health organizations and the community - may increase HPV vaccine uptake in this population.

Potential barriers to HPV vaccine provision among medical practices in an area with high rates of cervical cancer.

PURPOSE: Potential barriers to widespread vaccination of adolescent girls against human papillomavirus (HPV) infection are poorly understood. We provide an overview of potential barriers to provision of HPV vaccine and empirical data on the concerns of medical practices that may inhibit HPV vaccine provision. METHOD: We conducted phone interviews with medical practices in rural areas in southeastern North Carolina with high rates of cervical cancer to assess 10 potential concerns about HPV vaccine provision. RESULTS: Concerns most commonly reported by medical practices (N = 71) were inadequate reimbursement (68%), high cost of the vaccine to patients (66%), and burden of determining insurance coverage (66%). Practices that were not providing the vaccine reported more concerns about HPV vaccine provision on average than practices providing the vaccine (6.0 vs. 4.5 concerns, p < .05). CONCLUSIONS: Medical practices' concerns about the HPV vaccine may be barriers to stocking it and, thus, to providing it to adolescents. Even providers who stock the vaccine reported concerns. Research is needed to address ways to ameliorate these medical practices' concerns and also to understand other potential barriers to vaccine coverage.

The potential health and economic benefits of preventing recurrent respiratory papillomatosis through quadrivalent human papillomavirus vaccination.

We estimated the health and economic benefits of preventing recurrent respiratory papillomatosis (RRP) through quadrivalent human papillomavirus (HPV) vaccination. We applied a simple mathematical model to estimate the averted costs and quality-adjusted life years (QALYs) saved by preventing RRP in children whose mothers had been vaccinated at age 12 years. Under base case assumptions, the prevention of RRP would avert an estimated USD 31 (range: USD 2-178) in medical costs (2006 US dollars) and save 0.00016 QALYs (range: 0.00001-0.00152) per 12-year-old girl vaccinated. Including the benefits of RRP reduced the estimated cost per QALY gained by HPV vaccination by roughly 14-21% in the base case and by <2% to >100% in the sensitivity analyses. More precise estimates of the incidence of RRP are needed, however, to quantify this impact more reliably.