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.

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.

Preclinical evaluation of two phylogenetically distant arenavirus vectors for the development of novel immunotherapeutic combination strategies for cancer treatment.

BACKGROUND: Engineered arenavirus vectors have recently been developed to leverage the body's immune system in the fight against chronic viral infections and cancer. Vectors based on Pichinde virus (artPICV) and lymphocytic choriomeningitis virus (artLCMV) encoding a non-oncogenic fusion protein of human papillomavirus (HPV)16 E6 and E7 are currently being tested in patients with HPV16+ cancer, showing a favorable safety and tolerability profile and unprecedented expansion of tumor-specific CD8+ T cells. Although the strong antigen-specific immune response elicited by artLCMV vectors has been demonstrated in several preclinical models, PICV-based vectors are much less characterized. METHODS: To advance our understanding of the immunobiology of these two vectors, we analyzed and compared their individual properties in preclinical in vivo and in vitro systems. Immunogenicity and antitumor effect of intratumoral or intravenous administration of both vectors, as well as combination with NKG2A blockade, were evaluated in naïve or TC-1 mouse tumor models. Flow cytometry, Nanostring, and histology analysis were performed to characterize the tumor microenvironment (TME) and T-cell infiltrate following treatment. RESULTS: Despite being phylogenetically distant, both vectors shared many properties, including preferential infection and activation of professional antigen-presenting cells, and induction of potent tumor-specific CD8+ T-cell responses. Systemic as well as localized treatment induced a proinflammatory shift in the TME, promoting the infiltration of inducible T cell costimulator (ICOS)+CD8+ T cells capable of mediating tumor regression and prolonging survival in a TC-1 mouse tumor model. Still, there was evidence of immunosuppression built-up over time, and increased expression of H2-T23 (ligand for NKG2A T cell inhibitory receptor) following treatment was identified as a potential contributing factor. NKG2A blockade improved the antitumor efficacy of artARENA vectors, suggesting a promising new combination approach. This demonstrates how detailed characterization of arenavirus vector-induced immune responses and TME modulation can inform novel combination therapies. CONCLUSIONS: The artARENA platform represents a strong therapeutic vaccine approach for the treatment of cancer. The induced antitumor immune response builds the backbone for novel combination therapies, which warrant further investigation.

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.

[Application of seamless phase â ¡/â ¢ design in vaccine clinical trials].

The seamless phase Ⅱ/Ⅲ design integrates independent phase Ⅱ and phase Ⅲ clinical trials into a continuous, phased adaptive clinical trial design. Compared with traditional independent phase Ⅱ and phase Ⅲ clinical trials, the seamless design offers significant advantages in accelerating drug or vaccine development and improving clinical trial efficiency. Currently, the application of this design in anti-tumor drug research is becoming increasingly mature, and it is gradually expanding to clinical trials of vaccines, including the 9-valent human papillomavirus vaccine, sabin strain inactivated polio vaccine, and others. This paper aims to clarify the seamless phase Ⅱ/Ⅲ design concept and offer valuable insights into its implementation. It accomplishes this by presenting a clinical trial example featuring a phase Ⅱ/Ⅲ seamless design for a 9-valent human papillomavirus vaccine. The article delves into the specific considerations and potential challenges related to implementing the seamless design, aiming to provide valuable insights for optimizing vaccine clinical trials within our country.

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.

An evaluation of the cost of human papilloma virus (HPV) vaccine delivery in Zambia.

BACKGROUND: Human papillomavirus (HPV) is a common sexually transmitted infection and the leading cause of cervical cancer. The HPV vaccine is a safe and effective way to prevent HPV infection. In Zambia, the vaccine is given during Child Health Week to girls aged 14 years who are in and out of school in two doses over two years. The focus of this evaluation was to establish the cost to administer a single dose of the vaccine as well as for full immunisation of two doses. METHODS: This work was part of a broader study on assessing HPV programme implementation in Zambia. For HPV costing aspect of the study, with a healthcare provider perspective and reference year of 2020, both top-down and micro-costing approaches were used for financial costing, depending on the cost data source, and economic costs were gathered as secondary data from Expanded Programme for Immunisation Costing and Financing Project (EPIC), except human resource costs which were gathered as primary data using existing Ministry of Health salary scales and reported time spent by different health cadres on activities related to HPV vaccination. Data was collected from eight districts in four provinces, mainly using a structured questionnaire, document reviews and key informant interviews with staff at national, provincial, district and health facility levels. Administrative coverage rates were obtained for each district. RESULTS: Findings show that schools made up 53.3% of vaccination sites, community outreach sites 30.9% and finally health facilities 15.8%. In terms of coverage for 2020, for the eight districts sampled, schools had the highest coverage at 96.0%. Community outreach sites were at 6.0% of the coverage and health facilities accounted for only 1.0% of the coverage. School based delivery had the lowest economic cost at USD13.2 per dose and USD 28.1 per fully immunised child (FIC). Overall financial costs for school based delivery were US$6.0 per dose and US$12.4 per FIC. Overall economic costs taking all delivery models into account were US$23.0 per dose and US$47.6 per FIC. The main financial cost drivers were microplanning, supplies, service delivery/outreach and vaccine co-financing; while the main economic cost drivers were human resources, building overhead and vehicles. Nurses, environmental health technicians and community-based volunteers spent the most time on HPV related vaccination activities compared to other cadres and represented the greatest human resource costs. CONCLUSIONS: The financial cost of HPV vaccination in Zambia aligns favourably with similar studies conducted in other countries. However, the economic costs appear significantly higher than those observed in most international studies. This discrepancy underscores the substantial strain placed on healthcare resources by the program, a burden that often remains obscured. While the vaccine costs are currently subsidized through the generous support of Gavi, the Vaccine Alliance, it's crucial to recognize that these expenses pose a considerable threat to long-term sustainability. Consequently, countries such as Zambia must proactively devise strategies to address this challenge.

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.