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.

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.

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.

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.

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.

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.

Facilitators and barriers of HPV vaccination: a qualitative study in rural Georgia.

INTRODUCTION: Human papillomavirus (HPV) vaccination protects against HPV-associated cancers and genital warts. Healthy People 2030 goal for HPV vaccine uptake is 80%, but as of 2021, only 58.5% of adolescents are up to date in Georgia. The purpose of the study is to assess the attitudes, vaccine practices, facilitators, and barriers to receiving the HPV vaccine in southwest Georgia. METHODS: We conducted 40 semi-structured interviews in the United States from May 2020-Feburary 2022 with three different audiences (young adults, parents, and providers and public health professionals) guided by the P3 (patient-, provider-, practice-levels) Model. The audiences were recruited by multiple methods including fliers, a community advisory board, Facebook ads, phone calls or emails to schools and health systems, and snowball sampling. Young adults and parents were interviewed to assess their perceived benefits, barriers, and susceptibility of the HPV vaccine. Providers and public health professionals were interviewed about facilitators and barriers of patients receiving the HPV vaccine in their communities. We used deductive coding approach using a structured codebook, two coders, analyses in MAXQDA, and matrices. RESULTS: Out of the 40 interviews: 10 young adults, 20 parents, and 10 providers and public health professionals were interviewed. Emerging facilitator themes to increase the uptake of the HPV vaccine included existing knowledge (patient level) and community outreach, providers' approach to the HPV vaccine recommendations and use of educational materials in addition to counseling parents or young adults (provider level) and immunization reminders (practice level). Barrier themes were lack of knowledge around HPV and the HPV vaccine (patient level), need for strong provider recommendation and discussing the vaccine with patients (provider level), and limited patient reminders and health education information around HPV vaccination (practice level). Related to socio-ecology, the lack of transportation and culture of limited discussion about vaccination in rural communities and the lack of policies facilitating the uptake of the HPV vaccine (e.g., school mandates) were described as challenges. CONCLUSION: These interviews revealed key themes around education, knowledge, importance of immunization reminders, and approaches to increasing the HPV vaccination in rural Georgia. This data can inform future interventions across all levels (patient, provider, practice, policy, etc.) to increase HPV vaccination rates in rural communities.

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.

[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.

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.

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.

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.

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.

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.