Choosing the Appropriate HPV Testing and Treatment Algorithm: What Works for Different Contexts?

Cervical cancer can be eliminated, and the global community intends to achieve this goal in the next century. For this to successfully occur, concerted efforts to implement and scale-up available, evidence-based strategies including human papillomavirus vaccination, screening and treatment of precancerous lesions, and early detection and treatment for invasive cancers is paramount. While the World Health Organization has offered technical guidance and recommendations on implementation, several questions remain unanswered and require urgent high-quality research to inform policy and practice. We discuss the findings from the Cervical Cancer Screening and Treatment Algorithms pilot study in the context of the evidence synthesis conducted for the second edition of the World Health Organization guidelines for screening and treatment of cervical precancer lesions for cervical cancer prevention. Policymakers at the national level must consider the weight of evidence with country-level resources to make decisions on screening, triage, and treatment approaches. See related article by Sebitloane et al., p. 779.

A multilevel intervention to promote HPV vaccination among young adults in Texas: protocol for a randomized controlled trial.

BACKGROUND: Human papillomavirus (HPV) infections can cause cancers of the cervix, vagina, vulva, penis, anus, and oropharynx. The most recently approved HPV vaccine, Gardasil-9, protects against HPV infection and can prevent HPV-associated invasive cancers. However, Gardasil-9 is one of the most underused vaccines in the US today. Young adults are at risk for HPV infection, but many are not vaccinated. This study uses a randomized controlled trial (RCT) to test an innovative multilevel intervention to increase HPV vaccination rates among young adults. In this paper, we describe the research protocol. METHODS: The study uses a two by three factorial design. A total of 1200 young adults in Texas, age 18-26 years, who have not been previously fully vaccinated against HPV will be randomly assigned to one of six conditions to receive: (1) standard CDC information about HPV vaccination (control); (2) video narratives about HPV vaccination; (3) written narratives about HPV vaccination; or (4-6) enhanced access to HPV vaccine combined with (4) standard CDC information, (5) video narratives, or (6) written narratives. The two primary outcomes are the rate of HPV vaccination initiation by 3-month follow-up and rate of HPV vaccination completion by 9-month follow-ups. We will determine the impact of the individual level intervention (i.e., persuasive narratives through video or written format), the systemic level intervention (i.e., enhanced access to HPV vaccines), and the combination of both levels, on HPV vaccination initiation and completion. We will also use purposive sampling to select participants to take part in semi-structured interviews/focus groups to better understand the mechanisms of the intervention. DISCUSSION: Recruitment and data collection began in March 2022. We expect to complete data collection by March 2026. We expect that narratives, enhanced access, and the combination of both will improve HPV vaccination initiation and completion rates among young adults. If proven successful, these individual- and system-level interventions can be easily disseminated in regions with low HPV vaccination rates to improve HPV vaccination, and ultimately decrease HPV-related cancer burden. TRIAL REGISTRATION: NCT05057312.

Inequities in human papillomavirus vaccination among children aged 9-14 years old under constrained vaccine supply in China.

BACKGROUND: Inequities in access to human papillomavirus (HPV) vaccine are becoming a growing critical issue globally. Few studies investigate the factors determining HPV vaccine uptake disparities when vaccine supply is constrained, especially in low- and middle-income countries. The aim of this study was to investigate inequities of HPV vaccination and related factors under the constrained vaccine supply in China. METHODS: A cross-sectional survey was conducted in a developed eastern coastal province and a developing western one in China between November and December 2022. Employing multistage stratified cluster random sampling, the study collected data from parents of children aged 9-14. Mixed-effects logistic regression models with school units as random effects were used for analysis. RESULTS: From 4,127 eligible parents (as vaccine decision makers for girls), 1,346 (32.6%) intended to vaccinate their daughters against HPV, of which 836 (62.1%) attempted to schedule a vaccination appointment. Only 16.4% succeeded in booking an appointment. More than half of the intended parents expected the imported 9-valent HPV vaccine. There were significant disparities in HPV vaccine awareness, intention, and vaccination behavior across educational, income, geographic, ethnic, gender, and health literacy levels. Vaccine awareness and intentions were higher among parents with higher socioeconomic status; however, girls from lower socioeconomic families were more likely to receive the HPV vaccine and had a higher domestically produced vaccination rate. Significant disparities exist in vaccination intentions and actual vaccination behaviors, primarily due to large supply constraints of the HPV vaccine. CONCLUSIONS: Sustained health education campaigns are needed to raise awareness of the HPV vaccine, improve health literacy, and decrease over-preference for the 9-valent HPV vaccine. A mother's HPV vaccination behavior was positively associated with increased intention and actual vaccination behavior for her daughter. This study advocates for complementary cervical cancer prevention programs targeting both mothers and daughters.

Strategies to accelerate the elimination of cervical cancer in British Columbia, Canada: a modelling study.

BACKGROUND: To eliminate cervical cancer in Canada by 2040, defined as an annual age-standardized incidence rate (ASIR) lower than 4.0 per 100 000 women, the Canadian Partnership Against Cancer (CPAC) identified 3 priorities for action: increasing human papillomavirus (HPV) vaccine coverage, implementing HPV-based screening and increasing screening participation, and improving follow-up after abnormal screen results. Our objective was to explore the impact of these priorities on the projected time to elimination of cervical cancer in British Columbia. METHODS: We used OncoSim-Cervical, a microsimulation model led and supported by CPAC and developed by Statistics Canada that simulates HPV transmission and the natural history of cervical cancer for the Canadian population. We updated model parameters to reflect BC's historical participation rates and program design. We simulated the transition to HPV-based screening and developed scenarios to explore the additional impact of achieving 90% vaccination coverage, 95% screening recruitment, 90% ontime screening, and 95% follow-up compliance. We projected cervical cancer incidence, ASIR, and year of elimination for the population of BC for 2023-2050. RESULTS: HPV-based screening at current vaccination, participation, and follow-up rates can eliminate cervical cancer by 2034. Increasing on-time screening and follow-up compliance could achieve this target by 2031. Increasing vaccination coverage has a small impact over this time horizon. INTERPRETATION: With the implementation of HPV-based screening, cervical cancer can be eliminated in BC before 2040. Efforts to increase screening participation and follow-up through this transition could potentially accelerate this timeline, but the transition from cytology- to HPV-based screening is fundamental to achieving this goal.

Reduced risk of CIN2+ recurrence in women immunized with a 9-valent HPV vaccine post-excision: Retrospective cohort study.

The main aim of our study was to investigate the specific contribution of a 9-valent human papillomavirus vaccine (9vHPV) to the recurrence risk of cervical intraepithelial neoplasia grade 2 or worse (CIN2+) in women vaccinated post-excision. Therefore, we conducted a retrospective monocentric cohort study in women aged 22-49 years undergoing conization between 2014 and 2023. The 9vHPV-vaccinated women were matched to unvaccinated women for age and follow-up duration in a 1:2 ratio to eliminate allocation bias. The risk of CIN2+ recurrence was estimated by the incidence rate ratio using Poisson regression with adjustment for comorbidities, smoking status, nulliparity, CIN grade, positive cone margin, and HPV genotypes. The CIN2+ recurrence rates in 147 women enrolled in the analysis were 18 and 2 cases per 100,000 person-days for unvaccinated and vaccinated women, respectively, during a mean follow-up period of 30 months (±22 months). A reduction in CIN2+ recurrences by 90% (95% confidence interval: 12-99%) was documented in 9vHPV-vaccinated participants compared to women undergoing only surgical excision. Moreover, vaccinated women with a positive cone margin showed a 42% (though non-significant) reduction in relapse (p = .661). Full post-conization vaccination with the 9vHPV contributed to an additional reduction in the risk of CIN2+ recurrence. This finding is consistent with current knowledge and suggests a high adjuvant effect of the 9vHPV vaccine.

Geospatial mapping of public sentiment and infodemic on human papillomavirus vaccination in India: An indication to formulation of strategies for effective implementation.

The implementation of Human Papillomavirus (HPV) vaccination is crucial for eliminating cervical cancer in India. The infodemic, characterised by misleading information, could hinder the successful implementation of the initiative. Misinformation related to the HPV vaccine, such as rumours, has been reported and circulated, contributing to an alarming pattern of vaccine hesitancy observed on social media. This study aimed to identify the public sentiment towards HPV vaccination based on the 'Behavioral and Social Drivers (BeSD)' framework through geospatial, content and sentiment analysis. A total of 1,487 tweets were extracted. After preprocessing, 1010 tweets were identified for sentiment and content analysis. The sentiments expressed towards the HPV vaccine are mixed, with a generally positive outlook on the vaccines. Within the population, there is a pervasive proliferation of misinformation, primarily focusing on vaccine safety and efficacy, contentious subjects, ethical considerations, and a prevalent sense of uncertainty in selecting the appropriate vaccine. These observations are crucial for developing targeted strategies to address public concerns and enhance vaccination rates. The insights gained from these results will guide policymakers, healthcare practitioners, and public health organisations to implement evidence-based interventions, thereby countering vaccine hesitancy and improving public health outcomes.

[Expert recommendation for real-world study on the application of human papillomavirus vaccine in the Yangtze River Delta region].

Cervical cancer has become a global public health problem that poses a serious threat to women's health. Human papillomavirus (HPV) vaccination is an important primary preventive measure for cervical cancer. With the accelerated application of the HPV vaccine in China, conducting real-world studies (RWS) on the application of HPV vaccines can guide the rational use of the vaccine, which is of great significance for the strategy and practice of accelerating the elimination of cervical cancer in China. The Yangtze River Delta Cervical Cancer and Female Lower Genital Tract Infection Prevention and Control Alliance and Yangtze River Delta Immunization Integration Working Group organized an expert group to develop the "Expert recommendation for real-world study on the application of HPV vaccine in the Yangtze River Delta region". Based on the current situation of medical informatization and HPV vaccination administration in China, as well as literature and cases from domestic and international studies, this study describes the data chain of HPV vaccination and evaluation, introduces the study design, study direction, database construction, data governance and statistical analysis of RWS, and provides expert recommendation on the problems in carrying out the practice of HPV vaccine RWS, aiming to guide the RWS of HPV vaccine application and promote the generation of real-world evidence (RWE) in China.

Human Papillomavirus vaccination coverage among the female population living in the state of Goiás, Brazil, 2014-2020: a time series study.

OBJECTIVE: To analyze the temporal trend of human papillomavirus (HPV) vaccination coverage among the female population aged 10 to 14 years, living in the state of Goiás, Brazil, between 2014 and 2022. METHODS: This was an ecological time series study using data from the Brazilian National Health System Information Technology Department (Departamento de Informática do Sistema Único de Saúde - DATASUS); the annual vaccination coverage rate was calculated based on the number of second doses administered; the trend of the rates was analyzed using the Prais-Winsten model. RESULTS: A total of 407,217 second doses of the quadrivalent HPV vaccine were administered to the female population aged 10-14 years, with annual vaccination coverage rates ranging from 12.3% (2019) to 30.0% (2015), and an annual percentage change (APC) of 0.7% (95%CI 0.9; 0.2; p-value = 0.030). CONCLUSION: In Góias state, the quadrivalent HPV vaccine coverage rate was below the national target (80%), showing a stationary trend in the time series.

Trends of cervical tumours amongst women from perspectives of demographic, socioeconomic and geographic indicators: retrospective ecological study in Czechia.

Introduction: For many infectious diseases, women are at higher risk and have a more severe disease course than men for many reasons, including biological differences, social inequalities, and restrictive cultural norms. The study focuses on infections with human papillomaviruses (HPV) in the form of cervical cancer as a gender-specific disease. The main goal is to evaluate cervical tumour incidence trends in the Czech female population in the HPV vaccination period 2012-2020 in relation to selected demographic, socioeconomic, and geographic indicators. Methods: This is a retrospective ecological study. Data from publicly available databases about the incidence and mortality of cervical tumours (C53 Malignant neoplasm of cervix uteri, D06 Carcinoma in situ of cervix uteri according to ICD 10) and HPV vaccination rate were analysed and compared with demographic, socioeconomic and territorial data. Associations were searched using correlation analysis. Results: There was a decreasing trend in the incidence of cervical cancer in the observed period. Regarding cervical tumours (C53, D06) and malignant neoplasm of cervix uteri incidence (C53), the decrease was approximately 11 and 20%, respectively. Differences between regions were observed in incidences and vaccination rates. Based on correlation analysis, indicators connected with urban/rural aspects, such as a share of urban population and population density, were statistically significant. The indicators related to higher cervical cancer incidence are the high unemployment rate of women, the high number of divorces, the high number of abortions, the high share of the urban population, the high number of students, and the high number of women with only primary education. On the other hand, the indicators related to lower cervical cancer incidence are the high gross domestic product (GDP), the high average gross monthly wage per employee, the high employment rate of women, the higher average age of mothers at birth, and the high number of women with tertiary education. Conclusion: Results underline the problem of economically disadvantaged regions and families. Increasing vaccination rates, promoting regular screening for cervical cancer, and supporting awareness in the population, especially in regions with higher incidence rates, should be priorities for public health efforts.

Actions speak louder than words; pediatricians, gynecologists, nurses, and other mothers' perspectives on the human papillomavirus vaccine: an Istanbul multicenter study.

Introduction: Gynecologists and pediatricians have an essential duty to prevent cervical cancer. In this study, we compared the compliance of gynecologists (n = 22) and pediatricians (n = 49) with nurse/midwife (n = 66) and non-medical moms (n = 120) with regards to cervical cancer precautions. Methods: A questionnaire was used to gather data on their demographics, personal vaccination and screening practices, children's immunization status, and awareness of cervical cancer prevention. Results: The findings demonstrated that gynecologists and pediatricians were better than others at understanding the risk factors and prevention of cervical cancer. It was noted that compared to other groups, physician mothers and their offspring had higher vaccination rates (n = 13, 18.3%; n = 10, 29.4%, respectively). Medical professionals typically provided thorough and accurate answers to informational questions. More frequent Pap smear tests were performed by gynecologists. It was noted that mothers who worked as pediatricians and nurses/midwives neglected their own screening needs. Discussion: This questionnaire survey sought to ascertain Istanbul's health professionals' present opinions regarding HPV vaccination. Healthcare professionals should be the first to receive information on HPV vaccination and cervical cancer incidence reduction. The public could then readily use them as an example.

Human papillomavirus infection (HPV) and pregnancy.

Human papillomavirus (HPV) is the most common sexually transmitted viral infection worldwide, which may result in the development in benign lesions or malignant tumors. The prevalence of HPV infection is twice as high in pregnancy as in non-pregnant women. Additionally, there is a risk of vertical transmission of HPV from mother to fetus during pregnancy or childbirth. Various studies have reported an increased risk of adverse pregnancy outcomes in HPV-positive women, including miscarriage, preterm birth, premature rupture of membranes, preeclampsia, fetal growth restriction, and fetal death. HPV vaccination is not currently recommended during pregnancy. On the other hand, there is no evidence linking HPV vaccination during pregnancy with adverse pregnancy outcomes and termination of pregnancy is not justified in this case.

Effect of the HPV vaccination programme on incidence of cervical cancer and grade 3 cervical intraepithelial neoplasia by socioeconomic deprivation in England: population based observational study.

OBJECTIVES: To replicate previous analyses on the effectiveness of the English human papillomavirus (HPV) vaccination programme on incidence of cervical cancer and grade 3 cervical intraepithelial neoplasia (CIN3) using 12 additional months of follow-up, and to investigate effectiveness across levels of socioeconomic deprivation. DESIGN: Observational study. SETTING: England, UK. PARTICIPANTS: Women aged 20-64 years resident in England between January 2006 and June 2020 including 29 968 with a diagnosis of cervical cancer and 335 228 with a diagnosis of CIN3. In England, HPV vaccination was introduced nationally in 2008 and was offered routinely to girls aged 12-13 years, with catch-up campaigns during 2008-10 targeting older teenagers aged <19 years. MAIN OUTCOME MEASURES: Incidence of invasive cervical cancer and CIN3. RESULTS: In England, 29 968 women aged 20-64 years received a diagnosis of cervical cancer and 335 228 a diagnosis of CIN3 between 1 January 2006 and 30 June 2020. In the birth cohort of women offered vaccination routinely at age 12-13 years, adjusted age standardised incidence rates of cervical cancer and CIN3 in the additional 12 months of follow-up (1 July 2019 to 30 June 2020) were, respectively, 83.9% (95% confidence interval (CI) 63.8% to 92.8%) and 94.3% (92.6% to 95.7%) lower than in the reference cohort of women who were never offered HPV vaccination. By mid-2020, HPV vaccination had prevented an estimated 687 (95% CI 556 to 819) cervical cancers and 23 192 (22 163 to 24 220) CIN3s. The highest rates remained among women living in the most deprived areas, but the HPV vaccination programme had a large effect in all five levels of deprivation. In women offered catch-up vaccination, CIN3 rates decreased more in those from the least deprived areas than from the most deprived areas (reductions of 40.6% v 29.6% and 72.8% v 67.7% for women offered vaccination at age 16-18 and 14-16, respectively). The strong downward gradient in cervical cancer incidence from high to low deprivation in the reference unvaccinated group was no longer present among those offered the vaccine. CONCLUSIONS: The high effectiveness of the national HPV vaccination programme previously seen in England continued during the additional 12 months of follow-up. HPV vaccination was associated with a substantially reduced incidence of cervical cancer and CIN3 across all five deprivation groups, especially in women offered routine vaccination.

Assessing the reduction of viral infectivity in HPV16/18-positive women after one, two, and three doses of Gardasil-9 (RIFT): Study protocol.

Human Papillomavirus (HPV) prophylactic vaccination has proven effective in preventing new infections, but it does not treat existing HPV infections or associated diseases. Hence, there is still an important reservoir of HPV in adults, as vaccination programs are mainly focused on young women. The primary objective of this non-randomized, open-label trial is to evaluate if a 3-dose regimen of Gardasil-9 in HPV16/18-positive women could reduce the infective capacity of their body fluids. We aim to assess if vaccine-induced antibodies could neutralize virions present in the mucosa, thus preventing the release of infective particles and HPV transmission to sexual partners. As our main endpoint, the E1^E4-HaCaT model will be used to assess the infectivity rate of cervical, anal and oral samples, obtained from women before and after vaccination. HPV DNA positivity, virion production, seroconversion, and the presence of antibodies in the exudates, will be evaluated to attribute infectivity reduction to vaccination. Our study will recruit two different cohorts (RIFT-HPV1 and RIFT-HPV2) of non-vaccinated adult women. RIFT-HPV1 will include subjects with an HPV16/18 positive cervical test and no apparent cervical lesions or cervical lesions eligible for conservative treatment. RIFT-HPV2 will include subjects with an HPV16/18 positive anal test and no apparent anal lesions or anal lesions eligible for conservative treatment, as well as women with an HPV16/18 positive cervical test and HPV-associated vulvar lesions. Subjects complying with inclusion criteria for both cohorts will be recruited to the main cohort, RIFT-HPV1. Three doses of Gardasil-9 will be administered intramuscularly at visit 1 (0 months), visit 2 (2 months) and visit 3 (6 months). Even though prophylactic HPV vaccines would not eliminate a pre-existing infection, our results will determine if HPV vaccination could be considered as a new complementary strategy to prevent HPV-associated diseases by reducing viral spread. Trial registration: https://clinicaltrials.gov/ct2/show/NCT05334706.

Overview of knowledge, attitudes and barriers associated with HPV vaccination in Beirut, Lebanon.

BACKGROUND: Human Papillomavirus (HPV), a prevalent sexually transmitted infection carrying significant risks ranging from benign lesions to various types of malignancies, represents a matter of great public health concern. Notably, most Arab countries lack public awareness campaigns or national immunization programs. This study aims at assessing the overall knowledge on HPV and HPV vaccination among the Lebanese population, exploring the prevalent attitude on the matter, and identifying barriers and misconceptions that prevent individuals from receiving the HPV vaccine. METHODS: A cross-sectional study was conducted in Beirut, on 201 participants aged between 18 and 36 years old. We performed ordinal analysis to assess the trend between Knowledge levels, attitude levels and hesitancy Levels. RESULTS: Majority of participants (77%) demonstrated a low level of knowledge on HPV vaccination, 50% held a positive attitude, with only 18.4% being already vaccinated. Negative trend was identified between levels of knowledge, attitude and hesitancy (gamma = -0.7415, p-value < 0.01; gamma= -0.58, p-value < 0.01 respectively). Unavailability or limited access to the vaccine, and misconceptions about HPV immunization were shown to be impeding vaccination. CONCLUSION: Analysis of our results strongly suggests that improving knowledge and attitudes is likely to foster trust and reduce hesitancy, thereby promoting higher vaccine uptake.

Enhanced cervical cancer and HIV interventions reduce the disproportionate burden of cervical cancer cases among women living with HIV: A modeling analysis.

INTRODUCTION: Women living with HIV experience heightened risk of cervical cancer, and over 50% of cases in Southern Africa are attributed to HIV co-infection. Cervical cancer interventions tailored by HIV status delivered with HIV antiretroviral therapy (ART) for treatment can decrease cancer incidence, but impact on HIV-related disparities remains understudied. METHODS: Using a dynamic model calibrated to KwaZulu-Natal, South Africa, we projected HIV prevalence, cervical cancer incidence, and proportion of cancer cases among women living with HIV between 2021-2071. Relative to the status quo of moderate intervention coverage, we modeled three additive scenarios: 1) ART scale-up only; 2) expanded human papillomavirus (HPV) vaccination, screening, and treatment; and 3) catch-up HPV vaccination and enhanced screening for women living with HIV. RESULTS: Under the status quo, HIV prevalence among women aged 15+ decreased from a median of 35% [Uncertainty Range (UR): 26-42%] in 2021 to 25% [19-34%] in 2071. The proportion of cervical cancer cases that were women living with HIV declined from 73% [63-86%] to 58% [47-74%], but incidence remained 4.3-fold [3.3-5.7] that of women without HIV. ART scale-up reduced HIV prevalence in 2071, but increased the incidence rate ratio to 5.2 [3.7-7.3]. Disparities remained after expanding cancer interventions for all women (incidence rate ratio: 4.8 [3.6-7.6]), while additional catch-up HPV vaccination and screening for women living with HIV decreased the incidence rate ratio to 2.7 [1.9-3.4] in 2071. CONCLUSIONS: Tailored cervical cancer interventions for women living with HIV can counteract rising cancer incidence incurred by extended life expectancy on ART and reduce disparate cancer burden.

Human papillomavirus and occupational exposure: The need for vaccine provision for healthcare providers.

To probe the understanding of healthcare providers regarding occupational exposure to human papillomavirus and their knowledge about human papillomavirus vaccination in relation to the American Society for Colposcopy and Cervical Pathology (ASCCP) recommendations. In this cross-sectional study, the healthcare providers at Mayo Clinic Arizona, Florida, and Minnesota were delivered an electronic survey. The survey was completed by 349 healthcare providers, with one respondent excluded for inconsistent entry. The mean age of respondents was 42.7 ± 10.9, and of those, 68% were female and 32% were male. Of the unvaccinated respondents, 43.3% were ≤ 45 y of age (eligible for vaccination), while those vaccinated formed 41% of the respondents. Healthcare providers are highly concerned about their cancer safety, as shown by their awareness of occupational human papillomavirus hazards and broad knowledge about vaccine efficacy. The use of personal protective equipment varied widely, including eyewear, double gloving, procedural face mask, N95 face mask, and/or nothing. Human papillomavirus and cancer risk was clearly perceived by healthcare providers. For professions, pairwise comparisons revealed that nurse practitioners, physician assistants, certified registered nurse anesthetists, and allied healthcare providers had lower scores than medical doctors. Despite the high level of understanding among healthcare providers of occupational human papillomavirus exposure, only a few of them knew of the recommendations of the ASCPP for vaccination of healthcare providers treating human papillomavirus-related diseases. In such cases, most of those surveyed embraced vaccination, which was considered 100% safe by medical doctors and allied health professionals.

A reactogenic "placebo" and the ethics of informed consent in Gardasil HPV vaccine clinical trials: A case study from Denmark.

BACKGROUND: Medical ethics guidelines require of clinical trial investigators and sponsors to inform prospective trial participants of all known and potential risks associated with investigational medical products, and to obtain their free informed consent. These guidelines also require that clinical research be so designed as to minimize harms and maximize benefits. OBJECTIVE: To examine Merck's scientific rationale for using a reactogenic aluminum-containing "placebo" in Gardasil HPV vaccine pre-licensure clinical trials. METHODS: We examined the informed consent form and the recruitment brochure for the FUTURE II Gardasil vaccine trial conducted in Denmark; and we interviewed several FUTURE II trial participants and their treating physicians. We also reviewed regulatory documentation related to Gardasil vaccine approval process and the guidelines on evaluation of adjuvants used in human vaccines. RESULTS: It was found that the vaccine manufacturer Merck made several inaccurate statements to trial participants that compromised their right to informed consent. First, even though the study protocol listed safety testing as one of the study's primary objectives, the recruitment brochure emphasized that FUTURE II was not a safety study, and that the vaccine had already been proven safe. Second, the advertising material for the trial and the informed consent forms stated that the placebo was saline or an inactive substance, when, in fact, it contained Merck's proprietary highly reactogenic aluminum adjuvant which does not appear to have been properly evaluated for safety. Several trial participants experienced chronic disabling symptoms, including some randomized to the adjuvant "placebo" group. CONCLUSION: In our view, the administration of a reactive placebo in Gardasil clinical trials was without any possible benefit, needlessly exposed study subjects to risks, and was therefore a violation of medical ethics. The routine use of aluminum adjuvants as "placebos" in vaccine clinical trials is inappropriate as it hinders the discovery of vaccine-related safety signals.

Addressing the burden of cervical cancer for Indigenous women in Latin America and the Caribbean: a call for action.

Cervical cancer, primarily caused by human papillomavirus (HPV) infection, poses a significant global health challenge. Due to higher levels of poverty and health inequities, Indigenous women worldwide are more vulnerable to cervical cancer than their non-Indigenous counterparts. However, despite constituting nearly 10% of the population in Latin America and the Caribbean (LAC), the true extent of the burden of cervical cancer among Indigenous people in this region remains largely unknown. This article reviews the available information on cervical cancer incidence and mortality, as well as HPV infection prevalence, among Indigenous women in LAC. The limited existing data suggest that Indigenous women in this region face a heightened risk of cervical cancer incidence and mortality compared to non-Indigenous women. Nevertheless, a substantial knowledge gap persists that must be addressed to comprehensively assess the burden of cervical cancer among Indigenous populations, especially through enhancing cancer surveillance across LAC countries. Numerous structural, social and cultural barriers hindering Indigenous women's access to HPV vaccination and cervical cancer screening worldwide have been identified and are reviewed in this article. The discussion highlights the critical role of culturally sensitive education, community engagement, and empowerment strategies in overcoming those barriers. Drawing insights from the success of targeted strategies in certain high-income countries, the present article advocates for research, policies and healthcare interventions tailored to the unique context of LAC countries.