Sociodemographics, behaviour and knowledge of first South African HPV-vaccine recipients.

BACKGROUND:  Infection with the human papillomavirus (HPV) is a necessary cause of cervical cancer and is one of the most prevalent sexually transmitted infections worldwide. Primary prevention strategies target reducing HPV acquisition through vaccination, limiting exposure (e.g. delayed sexual debut, barrier contraception) and health education focusing on sexual behaviour and tobacco use. METHODS:  The ImmunoVACCS study, conducted from 2019 to 2022 in two provinces in South Africa, examined sociodemographic characteristics, sexual practices, and knowledge of cervical cancer and the HPV vaccine among young female vaccine recipients. It encompassed participants from the previously conducted vaccine implementation trials, VACCS 1 and VACCS 2 (2011-2014). Recruitment involved telephonic contact with eligible potential participants. Data were collected through self-administered questionnaires. RESULTS:  One hundred and eleven participants took part in the current study (median age: 20 years; age range: 16-22 years). Most sexually active participants had their first engagement in secondary school (96.2%), and 77.2% used contraception during their last sexual activity. Knowledge gaps were evident, with only 13.5% recognising cervical cancer's cervix origin and 3.6% attributing it to a virus. Despite this, 70.3% had heard of a vaccine for cervical cancer. Less than half knew about the importance of regular Pap smears (49.5%), vaccine protection (44.1%) or condom use (20.7%) against HPV and cervical cancer. CONCLUSION:  The current study demonstrates that young women still lack complete information on cervical cancer and its risk factors even after receiving health education linked with vaccination.Contribution: This study underscores the necessity of ongoing education about HPV, its risks and preventive measures among young women to combat cervical cancer.

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.

Using electronic health records to evaluate the adherence to cervical cancer prevention guidelines: A cross-sectional study.

OBJECTIVE: The fight against cervical cancer requires effective screening together with optimal and on-time treatment along the care continuum. We examined the impact of cervical cancer testing and treatment guidelines on testing practices, and follow-up adherence to guidelines. METHODS: Data from Estonian electronic health records and healthcare provision claims for 50,702 women was used. The annual rates of PAP tests, HPV tests and colposcopies during two guideline periods (2nd version 2012-2014 vs 3rd version 2016-2019) were compared. To assess the adherence to guidelines, the subjects were classified as adherent, over- or undertested based on the timing of the appropriate follow-up test. RESULTS: The number of PAP tests decreased and HPV tests increased during the 3rd guideline period (p < 0.01). During the 3rd guideline period, among 21-29-year-old women, the adherence to guidelines ranged from 38.7% (44.4…50.1) for ASC-US to 73.4% (62.6…84.3) for HSIL and among 30-59-year-old from 49.0% (45.9…52.2) for ASC-US to 65.7% (58.8…72.7) for ASCH. The highest rate of undertested women was for ASC-US (21-29y: 25.7%; 30-59y: 21.9%). The rates of over-tested women remained below 12% for all cervical pathologies observed. There were 55.2% (95% CI 49.7…60.8) of 21-24-year-olds and 57.1% (95% CI 53.6…60.6) of 25-29-year-old women who received HPV test not adherent to guidelines. CONCLUSIONS: Our findings highlighted some shortcomings in guideline adherence, especially among women under 30. The insights gained from this study help to improve the quality of care and, thus, reduce cervical cancer incidence and mortality.

Benefits, challenges, and strategies related to using presumptive recommendations for HPV vaccination: A qualitative study with rural and non-rural-serving primary care professionals.

HPV vaccination coverage remains far below the national target of 80% among US adolescents, particularly in rural areas, which have vaccine uptake rates that are 10% points lower than non-rural areas on average. Primary care professionals (PCPs) can increase coverage by using presumptive recommendations to introduce HPV vaccination in a way that assumes parents want to vaccinate. Through semi-structured interviews, we explored PCPs' experiences and perceptions of using presumptive recommendations in rural- and non-rural-serving primary care clinics in North Carolina. Thematic analysis revealed that most PCPs in rural and non-rural contexts used presumptive recommendations and felt the strategy was an effective and concise way to introduce the topic of HPV vaccination to parents. At the same time, some PCPs raised concerns about presumptive recommendations potentially straining relationships with certain parents, including those who had previously declined HPV vaccine or who distrust medical authority due to their past experiences with the healthcare system. PCPs dealt with these challenges by using a more open-ended approach when introducing HPV vaccination to parents. In conclusion, our findings suggest that PCPs in both rural and non-rural settings see value in using presumptive recommendations to introduce HPV vaccination, but to adequately address concerns and ensure increased HPV vaccine uptake, PCPs can use simple and culturally sensitive language to ensure fully informed consent and to maintain parental trust. And to further strengthen HPV vaccine discussions, PCPs can utilize other effective HPV communication techniques, like the Announcement Approach, in discussing HPV vaccinations with hesitant parents.

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.

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.

[Research progress on the differences between T and B cell responses to three different forms of human papilloma virus (HPV) vaccination].

One of the most prevalent malignancies in women is cervical cancer. Cervical cancer is mostly brought on by chronic high-risk human papillomavirus 16 (HPV16) and HPV18 infection. Currently, the widely used HPV vaccines are the bivalent Cervarix, the tetravalent Gardasil, and the 9-valent Gardasil-9.There are differences in T cell effector molecule changes, B cell antibody level, duration, age and the injection after vaccination of the three vaccines.

[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.

Concomitant human papillomavirus (HPV) vaccination and screening for elimination of HPV and cervical cancer.

HPV vaccination with concomitant HPV-based screening of young women has been proposed for faster cervical cancer elimination. We describe the baseline results of a population-based trial of this strategy to reduce the incidence of HPV. All 89,547 women born 1994-1999 and resident in the capital region of Sweden were personally invited to concomitant HPV vaccination and HPV screening with 26,125 women (29.2%) enrolled between 2021-05-03 and 2022-12-31. Baseline HPV genotyping of cervical samples from the study participants finds, compared to pre-vaccination prevalences, a strong decline of HPV16 and 18 in birth cohorts previously offered vaccination, some decline for cross-protected HPV types but no decline for HPV types not targeted by vaccines. Our dynamic transmission modelling predicts that the trial could reduce the incidence of high-risk HPV infections among the 1994-1998 cohorts by 62-64% in 3 years. Baseline results are prevalences of HPV infection, validated transmission model projections, and power estimates for evaluating HPV incidence reductions at follow-up (+/-0.1% with 99.9% confidence). In conclusion, concomitant HPV vaccination and HPV screening appears to be a realistic option for faster cervical cancer elimination. Clinicaltrials.gov identifier: NCT04910802; EudraCT number: 2020-001169-34.

The Role of Scientific Research in Human Papillomavirus Vaccine Discussions on Twitter: Social Network Analysis.

BACKGROUND: Attitudes toward the human papillomavirus (HPV) vaccine and accuracy of information shared about this topic in web-based settings vary widely. As real-time, global exposure to web-based discourse about HPV immunization shapes the attitudes of people toward vaccination, the spread of misinformation and misrepresentation of scientific knowledge contribute to vaccine hesitancy. OBJECTIVE: In this study, we aimed to better understand the type and quality of scientific research shared on Twitter (recently rebranded as X) by vaccine-hesitant and vaccine-confident communities. METHODS: To analyze the use of scientific research on social media, we collected tweets and retweets using a list of keywords associated with HPV and HPV vaccines using the Academic Research Product Track application programming interface from January 2019 to May 2021. From this data set, we identified tweets referring to or sharing scientific literature through a Boolean search for any tweets with embedded links, hashtags, or keywords associated with scientific papers. First, we used social network analysis to build a retweet or reply network to identify the clusters of users belonging to either the vaccine-confident or vaccine-hesitant communities. Second, we thematically assessed all shared papers based on typology of evidence. Finally, we compared the quality of research evidence and bibliometrics between the shared papers in the vaccine-confident and vaccine-hesitant communities. RESULTS: We extracted 250 unique scientific papers (including peer-reviewed papers, preprints, and gray literature) from approximately 1 million English-language tweets. Social network maps were generated for the vaccine-confident and vaccine-hesitant communities sharing scientific research on Twitter. Vaccine-hesitant communities share fewer scientific papers; yet, these are more broadly disseminated despite being published in less prestigious journals compared to those shared by the vaccine-confident community. CONCLUSIONS: Vaccine-hesitant communities have adopted communication tools traditionally wielded by health promotion communities. Vaccine-confident communities would benefit from a more cohesive communication strategy to communicate their messages more widely and effectively.

Sexually transmitted infections and the HPV-related burden: evolution of Italian epidemiology and policy.

Sexually transmitted infections (STIs) are a major public health problem worldwide, with a high prevalence between the ages of 15 and 25 in most Western countries. High notification rates of chlamydia, gonorrhea, and syphilis are reported in the WHO European Region, with differences between countries. In Italy, the total number of STIs alerts increased by 18% from 2020 to 2021. HPV is the most common sexually transmitted infection; globally one in seven women is infected by this virus, and certain sexual behaviors are important risk factors for HPV-related cancers, particularly cervical cancer (CC), anogenital cancers and cancers of the head and neck. The burden of CC is relevant worldwide, in particular in Europe CC is the third leading cause of cancer-related deaths in women aged 15-44. This HPV-related tumor is preventable through a combined strategy of vaccination and screening for precursor lesions. In Italy, the coverage of organized screening varies from region to region and the average HPV vaccination rate is still far from the expected optimal threshold of 95% at the age of 12. To address the challenges of health promotion and HPV prevention, priority actions are needed such as: promoting education and information at every level, from schools to healthcare professionals. In Italy, education of adolescents on sexual and reproductive health, still remains critical, regionally inhomogeneous and much lower than in other European countries. Equitable measures need to be taken, and schools are an important place for health promotion activities.

Human papillomavirus, oropharyngeal cancer, and the latest vaccine: considerations for oral healthcare providers.

Human papillomavirus (HPV) is associated with both benign and malignant disorders, such as genital warts and a variety of cancers, including oropharyngeal squamous cell carcinomas (OPSCCs). The current 9-valent HPV vaccine (Gardasil 9) protects against high-risk strains that have been shown to cause OPSCC, and widespread vaccination should reduce the rate of all HPV-associated cancers. HPV-related OPSCCs differ from non-HPV-related OPSCCs in their clinical presentations and responsiveness to treatment. To provide oral healthcare providers with a basis for effective com-munication with patients, this article will examine the evolution of the HPV vaccination schedule and the role of the HPV vaccine in the prevention of OPSCCs.

Cervical Cancer Stigma Among Caribbean Population: A Descriptive Paper.

Objectives: Cervical cancer prevention practices are desperately low in the Caribbean. This study aims to describe the cervical cancer stigma and to evaluate the influence of the prevention practices among the Caribbean non-patient population in Jamaica, Grenada, Trinidad and Tobago. Methods: A cross-sectional study involving 1,207 participants was conducted using a culturally trans-created Cancer Stigma Scale for the Caribbean context and supplemented with questions on cervical cancer and HPV/HPV vaccine knowledge and beliefs. Data collection took place online from October 2022 to March 2023. Results: Participants are young, single, well-educated, and have stable financial resources. Over a quarter (26.4%) agreed women with cervical cancer are more isolated in their country. Almost half (47%) of respondents agreed cultural background plays a big part in how they feel about illness and getting well. One in six participants believe women with cervical cancer are treated with less respect than usual by others in their country. Conclusion: Cancer stigma of cervical cancer exists in Jamaica, Trinidad and Tobago, and Grenada. Particularly, cultural background and social norms are closely linked to stigma.

Willingness and hesitancy towards the governmental free human papillomavirus vaccination among parents of eligible adolescent girls in Shenzhen, Southern China.

BACKGROUND: Since 2020, China has actively promoted HPV vaccination for eligible adolescent girls through various pilot programmes. This study investigated parental willingness and hesitancy towards the government-sponsored, free human papillomavirus (HPV) vaccination for eligible adolescent girls in Shenzhen, Southern China. METHODS: From June to August 2022, a cross-sectional survey was conducted with parents of girls entering Grade 7, employing an adapted Vaccine Hesitancy Scale to assess vaccine hesitancy and logistic regression to identify factors influencing willingness to accept the free domestic vaccines. RESULTS: Although only 3.4% of the 2856 respondents had their daughters vaccinated against HPV prior to the survey, 91.7% were willing to utilise the governmental vaccination services. Parents with children in public schools (χ2 = 20.08, p < 0.001), those with more secure medical insurance (χ2 = 4.97, p = 0.026), and parents who had received an HPV vaccine themselves (χ2 = 28.829, p < 0.001) showed more reluctance towards the free vaccines. Vaccine hesitancy was presented in a mere 2.1% but was a significant predictor of vaccine refusal, even after adjusting for multiple factors (adjusted OR = 15.98, 95% CI: 9.06, 28.20). Notably, about four-fifths of parents of unvaccinated daughters harboured concerns about the safety and efficacy of the domestic vaccine. CONCLUSIONS: Although parents show a strong inclination to utilise the government vaccination services, their vaccine hesitancy, driven by safety concerns and a preference for imported vaccines, remains a significant barrier for rolling out vaccination coverage. This study highlights the need for multifaceted intervention strategies that address these issues to enhance HPV vaccine uptake effectively.

Pattern of multiple human papillomavirus infection and type competition: An analysis in healthy Chinese women aged 18-45 years.

To assess the pattern of multiple human papillomavirus infection to predict the type replacement postvaccination. A total of 7372 women aged 18-45y from a phase III trial of an Escherichia coli-produced HPV-16/18 vaccine were analyzed at enrollment visit before vaccination. Hierarchical multilevel logistic regression was used to evaluate HPV vaccine type and nonvaccine-type interactions with age as a covariate. Binary logistic regression was construed to compare multiple infections with single infections to explore the impact of multiple-type infections on the risk of cervical disease. Multiple HPV infections were observed in 25.2% of HPV-positive women and multiple infections were higher than expected by chance. Statistically significant negative associations were observed between HPV16 and 52, HPV18 and HPV51/52/58, HPV31 and HPV39/51/52/53/54/58, HPV33 and HPV52/58, HPV58 and HPV52, HPV6 and HPV 39/51/52/53/54/56/58. Multiple HPV infections increased the risk of CIN2+ and HSIL+, with the ORs of 2.27(95%CI: 1.41, 3.64) and 2.26 (95%CI: 1.29, 3.95) for multiple oncogenic HPV infection separately. However, no significant evidence for the type-type interactions on risk of CIN2+ or HSIL+. There is possibility of type replacement between several pairs of vaccine and nonvaccine HPV type. Multiple HPV infection increased the risk of cervical disease, but coinfection HPV types seem to follow independent disease processes. Continued post-vaccination surveillance for HPV 51/52/58 types and HPV 39/51 types separately was essential after the first and second generation of HPV vaccination implementation in China.

Impact of a carrageenan gel on viral load of genital human papillomavirus infections in sexually active women: Findings from the Carrageenan-gel Against Transmission of Cervical Human papillomavirus (CATCH) trial.

Previous research has shown that women's use of a carrageenan gel reduces the risk of acquiring genital human papillomavirus (HPV) infections but does not help to clear existing ones. Although gel use may not result in complete clearance, it may decrease the viral load of HPV infections. We tested this hypothesis in the Carrageenan-gel Against Transmission of Cervical Human papillomavirus (CATCH) randomized controlled trial. Participants of the CATCH study were selected for viral load testing if they had completed the first four study visits and tested positive for HPV42 or HPV51 in at least one of these visits. HPV42 and HPV51 were chosen as they were among the most abundant low- and high-risk types, respectively, in the study sample. We measured viral load with a type-specific real-time polymerase chain reaction. Results were displayed using summary statistics. Of 461 enrolled participants, 39 were included in the HPV42 analysis set and 56 in the HPV51 analysis set. The median time between visits 1 and 4 was 3.7 months. The viral load (copies/cell) of HPV42 ranged from <0.001 to 13 434.1, and that of HPV51 from <0.001 to 967.1. The net median change in HPV42 viral load over all four visits was -1.04 copies/cell in the carrageenan and -147 copies/cell in the placebo arm (Wilcoxon rank sum test, p = 0.26). There was no net median change in HPV51 viral load over all four visits in either arm (p = 0.45). The use of a carrageenan-based gel is unlikely to reduce the viral load of HPVs 42 or 51.

High burden of human papillomavirus infection among men in Guangzhou, South China: Implications for HPV vaccination strategies.

The epidemiological and clinical aspects of Human Papillomavirus (HPV) infection in women have been extensively studied. However, there is a lack of information regarding HPV characteristics in males. In this study, we conducted a retrospective and observational study of 3737 consecutive male individuals attending outpatient clinics of Guangdong Women and Children Hospital from 2012 to 2023 in Guangzhou, South China, to determine the age- and genotype-specific prevalence of HPV in men. The results showed the overall prevalence of HPV among men was 42.15% (1575/3737), with variations ranging from 29.55% to 81.31% across distinct diagnostic populations. Low-risk HPV6 (15.47%), HPV11 (8.94%), and high-risk HPV52 (5.51%) were the most common types. The annual HPV prevalence decreased significantly (Z = -3.882, p < .001), ranging from 31.44% to 52.90%. 28.77% (1075/3737) of men manifested infection with a singular HPV type, predominantly identified as a low-risk type. The age-specific distribution of HPV infections revealed distinctive peaks in the < 25 y age group (47.60%, 208/437) and the 40-44 y age group (44.51%, 154/346). Notably, the positive rate of Chlamydia trachomatis was significantly higher among HPV-positive individuals in comparison to HPV-negatives (16.14% vs. 11.25%, p < .05). Our findings reveal a substantial prevalence of HPV infection among outpatient men in Guangzhou, South China. It is recommended to consider the inclusion of HPV vaccination for adolescent males in national immunization schedules, once an adequate supply of vaccines is accessible.

HPV-specific antibodies in female genital tract secretions captured via first-void urine retain their neutralizing capacity.

Human papillomavirus (HPV) vaccines, primarily relying on neutralizing antibodies, have proven highly effective. Recently, HPV-specific antibodies have been detected in the female genital tract secretions captured by first-void urine (FVU), offering a minimally invasive diagnostic approach. In this study, we investigated whether HPV16-specific antibodies present in FVU samples retain their neutralizing capacity by using pseudovirion-based neutralization assays. Paired FVU and serum samples (vaccinated n = 25, unvaccinated n = 25, aged 18-25) were analyzed using two orthogonal pseudovirion-based neutralization assays, one using fluorescence microscopy and the other using luminescence-based spectrophotometry. Results were compared with HPV16-specific IgG concentrations and correlations between neutralizing antibodies in FVU and serum were explored. The study demonstrated the presence of neutralizing antibodies in FVU using both pseudovirion-based neutralization assays, with the luminescence-based assay showing higher sensitivity for FVU samples, while the fluorescence microscopy-based assay exhibited better specificity for serum and overall higher reproducibility. High Spearman correlation values were calculated between HPV16-IgG and HPV16-neutralizing antibodies for both protocols (rs: 0.54-0.94, p < .001). Significant Spearman correlations between FVU and serum concentrations were also established for all assays (rs: 0.44-0.91, p < .01). This study demonstrates the continued neutralizing ability of antibodies captured with FVU, supporting the hypothesis that HPV vaccination may reduce autoinoculation and transmission risk to the sexual partner. Although further protocol optimizations are warranted, these findings provide a foundation for future research and larger cohort studies that could have implications for the optimal design, evaluation, and implementation of HPV vaccination programs.

Risk of progression of cervical intraepithelial neoplasia grade 2 in human papillomavirus-vaccinated and unvaccinated women: a population-based cohort study.

BACKGROUND: Many countries have implemented active surveillance (ie, leaving the lesion untreated) as an option among younger women with cervical intraepithelial neoplasia grade 2 because regression rates are high and excisional treatment increases the risk for preterm birth in subsequent pregnancies. However, early identification of women at increased risk for progression to cervical intraepithelial neoplasia grade 3 or worse is important to ensure timely treatment. Because women who have received a human papillomavirus vaccine have a lower risk for cervical cancer, they may have a lower risk for progression of untreated cervical intraepithelial neoplasia grade 2 to cervical intraepithelial neoplasia grade 3 or worse. OBJECTIVE: This study aimed to investigate if women who received a human papillomavirus vaccine and who are undergoing active surveillance for cervical intraepithelial neoplasia grade 2 are less likely to progress to cervical intraepithelial neoplasia grade 3 or worse when compared with women who did not receive the vaccine. STUDY DESIGN: We conducted a population-based cohort study in Denmark using data from national health registers. We identified all women aged 18 to 40 years who were undergoing active surveillance for cervical intraepithelial neoplasia grade 2 from January 1, 2007, to December 31, 2020. Women with a previous record of cervical intraepithelial neoplasia grade 2 or worse, hysterectomy, or a loop electrosurgical excision procedure were excluded. Exposure was defined as having received ≥1 dose of a human papillomavirus vaccine at least 1 year before the cervical intraepithelial neoplasia grade 2 diagnosis. We used cumulative incidence functions to estimate the risk for progression to cervical intraepithelial neoplasia grade 3 or worse within 28 months using hysterectomy, emigration, and death as competing events. We used modified Poisson regression to calculate crude and adjusted relative risks of progression during the 28-month surveillance period. Results were stratified by age at vaccination and adjusted for index cytology, disposable income, and educational level. RESULTS: The study population consisted of 7904 women of whom 3867 (48.9%) were vaccinated at least 1 year before a diagnosis of cervical intraepithelial neoplasia grade 2. At the time of cervical intraepithelial neoplasia grade 2 diagnosis, women who were vaccinated were younger (median age, 25 years; interquartile range, 23-27 years) than those who were not (median age, 29 years; interquartile range, 25-33 years). The 28-month cumulative risk for cervical intraepithelial neoplasia grade 3 or worse was significantly lower among women who were vaccinated before the age of 15 years (22.9%; 95% confidence interval, 19.8-26.1) and between the ages of 15 and 20 years (31.5%; 95% confidence interval, 28.8-34.3) when compared with women who were not vaccinated (37.6%; 95% confidence interval, 36.1-39.1). Thus, when compared with women who were not vaccinated, those who were vaccinated before the age of 15 years had a 35% lower risk for progression to cervical intraepithelial neoplasia grade 3 or worse (adjusted relative risk, 0.65; 95% confidence interval, 0.57-0.75), whereas women who were vaccinated between the ages of 15 and 20 years had a 14% lower risk (adjusted relative risk, 0.86; 95% confidence interval, 0.79-0.95). For women who were vaccinated after the age of 20 years, the risk was comparable with that among women who were not vaccinated (adjusted relative risk, 1.02; 95% confidence interval, 0.96-1.09). CONCLUSION: Women who were vaccinated and who were undergoing active surveillance for cervical intraepithelial neoplasia grade 2 had a lower risk for progression to cervical intraepithelial neoplasia grade 3 or worse during 28 months of follow-up when compared with women who were not vaccinated but only if the vaccine was administered by the age of 20 years. These findings may suggest that the human papillomavirus vaccination status can be used for risk stratification in clinical management of cervical intraepithelial neoplasia grade 2.