Human papillomavirus vaccination coverage among young women in the three sub-Saharan African countries using Demographic and Health Surveys data.

Cervical cancer is the fourth most common cancer, with 99% of cases linked to human papillomavirus (HPV) infection. It reflects global inequity as its burden is highest in low- and middle-income countries. The aim of this study was to determine the HPV vaccination coverage and its determinant factors among young women in the three sub-Saharan African countries. Data from the Demographic and Health Surveys among three sub-Saharan African countries were used for analysis. A total of 4,952 women were included in the study. Stata 14 was used to analyze the data. The determinants of the outcome variable were identified using a multilevel mixed-effects logistic regression model. Factors with p-values < 0.05 at 95% confidence interval were declared statistically significant. About 7.5% young women were vaccinated for HPV vaccine against cervical cancer in the current study. Younger age, use of internet, rich economic class, and individual-level media exposure were found to be favorable conditions, whereas being employed was negatively associated with HPV vaccination. Only few segments of young women in these three countries got HPV vaccination. The authors recommend that increasing internet use, media exposure, and economic level of young women will increase the HPV vaccination rates. Furthermore, creating awareness among employed women will also increase the possibility of HPV vaccination.

Attitude to cervical cancer screening and human papillomavirus testing experience in self-sampled Nigerian women.

Background: Cervical cancer is a disease of major public health significance which can be prevented by adequate screening. Objective: This study assessed the level of cervical cancer knowledge, attitude to screening and human papillomavirus testing experience in women who self-sampled for cervical cancer screening. Methods: A descriptive cross-sectional study involving 790 women that had human papilloma virus (HPV) testing at the gynae-oncology unit of the Lagos State University Teaching Hospital. Participants were assessed of their cervical cancer screening knowledge, attitude and HPV testing experience. High risk HPV (hr-HPV) nucleic acid testing was funded by the Clinton Health Access Initiative. Results: Majority (76.71%) of the respondents exhibited a high level of knowledge of cervical cancer, its causes, risk factors and prevention; and a positive experience with HPV self-sampling reported in 98.1%. hr-HPV positive rate was 13.4%. The most common reason (43%) for not having a cervical screening done was lack of a doctor's request. The most commonly known method of cervical screening by the respondents was Pap Smear test (55.31%). Conclusion: There is need for more education to improve the level of awareness and uptake of hr-HPV testing for cervical cancer in Lagos. Health care providers are not offering cervical cancer screening enough and this needs to be explored more in future studies.

Analysis of human papillomavirus type 16 E4, E5 and L2 gene variations among women with cervical infection in Xinjiang, China.

BACKGROUND: There is a high incidence of cervical cancer in Xinjiang. Genetic variation in human papillomavirus may increase its ability to invade, spread, and escape host immune response. METHODS: HPV16 genome was sequenced for 90 positive samples of HPV16 infection. Sequences of the E4, E5 and L2 genes were analysed to reveal sequence variation of HPV16 in Xinjiang and the distribution of variation among the positive samples of HPV16 infection. RESULTS: Eighty-one of the 90 samples of HPV16 infection showed variation in HPV16 E4 gene with 18 nucleotide variation sites, of which 8 sites were synonymous variations and 11 missense variations. 90 samples of HPV16 infection showed variation in HPV16 E5 and L2 genes with 16 nucleotide variation sites (6 synonymous, 11 missense variations) in the E5 gene and 100 nucleotide variation sites in L2 gene (37 synonymous, 67 missense variations). The frequency of HPV16 L2 gene missense variations G3377A, G3599A, G3703A, and G3757A was higher in the case groups than in the control groups. CONCLUSIONS: Phylogenetic tree analysis showed that 87 samples were European strains, 3 cases were Asian strains, there were no other variations, and G4181A was related to Asian strains. HPV16 L2 gene missense variations G3377A, G3599A, G3703A, and G3757A were significantly more frequent in the case groups than in the control groups.

Tirbanibulin decreases cell proliferation and downregulates protein expression of oncogenic pathways in human papillomavirus containing HeLa cells.

Tirbanibulin 1% ointment is a synthetic antiproliferative agent approved in 2021 by the European Union for treating actinic keratoses (AK). Topical tirbanibulin has clinically resolved HPV-57 ( +) squamous cell carcinoma (SCC), HPV-16 ( +) vulvar high-grade squamous intraepithelial lesion, epidermodysplasia verruciformis, and condyloma. We examined how tirbanibulin might affect HPV oncoprotein expression and affect other cellular pathways involved in cell proliferation and transformation. We treated the HeLa cell line, containing integrated HPV-18, with increasing doses of tirbanibulin to determine the effects on cell proliferation. Immunoblotting was performed with antibodies against the Src canonical pathway, HPV 18 E6 and E7 transcription regulation, apoptosis, and invasion and metastasis pathways. Cell proliferation assays with tirbanibulin determined the half-maximal inhibitory concentration (IC50) of HeLa cells to be 31.49 nmol/L. Increasing concentrations of tirbanibulin downregulates the protein expression of Src (p < 0.001), phospho-Src (p < 0.001), Ras (p < 0.01), c-Raf (p < 0.001), ERK1 (p < 0.001), phospho-ERK1 (p < 0.001), phospho-ERK2 (p < 0.01), phospho-Mnk1 (p < 0.001), eIF4E (p < 0.01), phospho-eIF4E (p < 0.001), E6 (p < 0.01), E7 (p < 0.01), Rb (p < 0.01), phospho-Rb (p < 0.001), MDM2 (p < 0.01), E2F1 (p < 0.001), phospho-FAK (p < 0.001), phospho-p130 Cas (p < 0.001), Mcl-1 (p < 0.01), and Bcl-2 (p < 0.001), but upregulates cPARP (p < 0.001), and cPARP/fPARP (p < 0.001). These results demonstrate that tirbanibulin may impact expression of HPV oncoproteins via the Src- MEK- pathway. Tirbanibulin significantly downregulates oncogenic proteins related to cell cycle regulation and cell proliferation while upregulating apoptosis pathways.

Tirbanibulin is Promising Novel Therapy for Human Papillomavirus (HPV)-associated Diseases.Tirbanibulin 1% ointment is an approved synthetic topical ointment for treating actinic keratoses (AK), a precancer of skin cancer. Topical tirbanibulin has previously been reported to clinically resolve human papillomavirus (HPV)-( +) diseases.In this study, we examine how tirbanibulin may affect the HPV and pathways associated with cancer.We treated the HeLa cell line to determine the effects on HPV cell proliferation. Increasing the concentration of tirbanibulin statistically significantly affected numerous cellular pathways often associated with cancer.These results demonstrate that tirbanibulin may impact expression of HPV oncoproteins and thereby kill cancer cells.

The Human Papillomavirus Enigma: A Narrative Review of Global Variations in Oropharyngeal Cancer Epidemiology and Prognosis.

Oropharyngeal cancers (OPCs) in Asia account for 42% of the global burden and over 50% of related deaths. Human papillomavirus (HPV) is involved in over 70% of OPC cases in the Western hemisphere, but its role in the Eastern hemisphere is unclear. This study reviews OPC epidemiology, including prevalence, etiological factors (such as smokeless tobacco and HPV), and their interaction. Among the SEAR countries, India had the highest incidence of HPV-related OPCs at 38.4%, while data were unavailable for most African countries, with only a 14% incidence reported. Conversely, the American region exhibited one of the highest HPV positivity rates, reaching up to 65% in different states of the USA, while Brazil reported an incidence of up to 38%. In the European Union, the UK had the highest incidence of HPV-associated OPC, reaching up to 52%. In the Western Pacific region, New Zealand demonstrated the highest incidence at up to 78%. Smokeless tobacco consumption was higher in SEAR countries, which had a relatively lower incidence of HPV infection, suggesting a negative correlation between the two. Based on our literature search, the most common detection methods used globally are immunohistochemistry for p16 and polymerized chain reaction. OPCs are a global health concern, and proper identification and classification are vital. HPV-driven cancers have better survival rates, emphasizing the need for focused research on specific problem areas based on the burden of HPV-positive or HPV-negative cancers.

Decoding dysregulated genes, molecular pathways and microRNAs involved in cervical cancer.

BACKGROUND: The present study aimed to identify dysregulated genes, molecular pathways, and regulatory mechanisms in human papillomavirus (HPV)-associated cervical cancers. We have investigated the disease-associated genes along with the Gene Ontology, survival prognosis, transcription factors and the microRNA (miRNA) that are involved in cervical carcinogenesis, enabling a deeper comprehension of cervical cancer linked to HPV. METHODS: We used 10 publicly accessible Gene Expression Omnibus (GEO) datasets to examine the patterns of gene expression in cervical cancer. Differentially expressed genes (DEGs), which showed a clear distinction between cervical cancer and healthy tissue samples, were analyzed using the GEO2R tool. Additional bioinformatic techniques were used to carry out pathway analysis and functional enrichment, as well as to analyze the connection between altered gene expression and HPV infection. RESULTS: In total, 48 DEGs were identified to be differentially expressed in cervical cancer tissues in comparison to healthy tissues. Among DEGs, CCND1, CCNA2 and SPP1 were the key dysregulated genes involved in HPV-associated cervical cancer. The five common miRNAs that were identified against these genes are miR-7-5p, miR-16-5p, miR-124-3p, miR-10b-5p and miR-27a-3p. The hub-DEGs targeted by miRNA hsa-miR-27a-3p are controlled by the common transcription factor SP1. CONCLUSIONS: The present study has identified DEGs involved in HPV-associated cervical cancer progression and the various molecular pathways and transcription factors regulating them. These findings have led to a better understanding of cervical cancer resulting in the development and identification of possible therapeutic and intervention targets, respectively.

The relationship between individuals' knowledge of human papillomavirus, attitudes towards HPV vaccination, and vaccine hesitancy: A cross-sectional study.

There are more than 207 types of Human Papillomavirus (HPV), most of which do not cause symptoms, lesions, or warts, and cause more than 600,000 cases of cancer annually. Purpose:This study was planned to elucidate the relationship between individuals' HPV knowledge, attitudes towards the HPV vaccine, and vaccine hesitancy. The research was conducted with 1011 people using a descriptive and correlational research design. Data collection tools included socio-demographic information survey, HPV Knowledge Scale, Carolina HPV Vaccination Attitudes Scale, and Vaccine Hesitancy Scale. The data was analyzed using the SPSS 26.0 package program. The average score was 11.68±7.23 on the HPV Knowledge Scale, 30.76±7.31 on the HPV Vaccine Attitude Scale, and 27.90±11.10 on the Vaccine Hesitancy Scale. While there was a very weak negative relationship between the participants HPV knowledge and HPV Vaccine Attitude scores, a weak positive relationship was found with vaccine hesitancy. A weak positive relationship was also detected between vaccine attitude and vaccine hesitancy (p<0.05). According to the regression model created in the study, HPV vaccination attitude was explained by the HPV Knowledge Scale and vaccine hesitancy at a rate of 22.5%. In line with the results, healthcare professionals need to raise awareness in the society and increase vaccination rates.

Il existe plus de 207 types de papillomavirus humain (HPV), dont la plupart ne causent pas de symptômes, de lésions ou de verrues, mais entraînent plus de 600 000 cas de cancer chaque année. Objectif : Cette étude a été planifiée pour élucider la relation entre les connaissances des individus sur le HPV, leurs attitudes envers le vaccin contre le HPV et l'hésitation vaccinale. La recherche a été menée auprès de 1011 personnes en utilisant un plan de recherche descriptif et corrélationnel. Les outils de collecte de données comprenaient un sondage d'informations sociodémographiques, l'Échelle de Connaissances sur le HPV, l'Échelle des Attitudes envers la Vaccination contre le HPV de la Caroline et l'Échelle d'Hésitation Vaccinale. Les données ont été analysées à l'aide du programme SPSS 26.0. Le score moyen était de 11,68 ± 7,23 à l'Échelle de Connaissances sur le HPV, de 30,76 ± 7,31 à l'Échelle des Attitudes envers la Vaccination contre le HPV, et de 27,90 ± 11,10 à l'Échelle d'Hésitation Vaccinale. Bien qu'il y ait eu une très faible relation négative entre les connaissances des participants sur le HPV et les scores d'attitude envers le vaccin contre le HPV, une faible relation positive a été trouvée avec l'hésitation vaccinale. Une faible relation positive a également été détectée entre l'attitude envers la vaccination et l'hésitation vaccinale (p<0,05). Selon le modèle de régression créé dans l'étude, l'attitude envers la vaccination contre le HPV était expliquée par l'Échelle de Connaissances sur le HPV et l'hésitation vaccinale à un taux de 22,5 %. Conformément aux résultats, les professionnels de la santé doivent sensibiliser la société et augmenter les taux de vaccination.

A transversal cross-sectional study of factors related to HPV vaccination status and cancer screening participation among French women aged 25-40.

BACKGROUND: In 2020, uterine cervical cancer (UCC) was the 12th most common cancer among women in France and the 4th worldwide. French health authorities wanted to increase Human Papilloma Virus (HPV) vaccination and screening rates. There were still many barriers to these measures among young women, their families, and health professionals and teachers. Between 2014 and 2019, international studies found inconsistent effects of HPV vaccination on UCC screening. In 2022, a survey was conducted among women aged 25 to 40 in the Nord-Pas-de-Calais region to assess participation 1) in HPV vaccination and its barriers, 2) in UCC screening as a function of HPV vaccination status. METHODS: Data were collected using an anonymous online questionnaire distributed by QR code in 80 general practices randomly selected in the Nord-Pas-de-Calais region between January and June 2022. Results were analyzed bivariately using the Chi2 test, multivariately when numbers allowed, and in age subgroups (sensitivity analysis). RESULTS: 407 complete questionnaires (for 602 participating women) were analyzed. In our sample, 41% of women aged 25 to 40 in the Nord-Pas-de-Calais region were vaccinated against HPV viruses in 2022. The risk factors for non-vaccination, after multivariable adjustment, were: the periods of eligibility for vaccination in the early days of French vaccination (2007-2012: odds ratio OR = 0.04 [95% CI, 0.02-0.09]; 2012-2017: OR = 0.5 [0.3-0.8]), information received from non-medical sources (OR = 0.3 [0.2-0.6]), and absence of information about vaccination (OR = 0.12 [0.05-0.27]). In our sample, 90% of women were screened for UCC. In bivariate analysis, women at risk of not being screened were those who were youngest, had been vaccinated against HPV, were not heterosexual, lived alone, had gynecological follow-up by their general practitioner, and did not have regular gynecological follow-up. Sensitivity analysis showed that the only risk factor significantly correlated with non-screening regardless of age group was lack of regular gynecological follow-up. CONCLUSIONS: Participation in HPV vaccination and UCC screening is improved by medical education and gynecological follow-up. This multicenter study, limited by the relative youth of vaccination in France, should be repeated after 2037 to assess the possible effect of vaccination on screening.

Cervical cancer screening and treatment costing in Senegal.

Introduction: in Senegal, cervical cancer is the leading cause of cancers among women. This study estimated the costs associated with cervical cancer screening and treatment for precancerous lesions from the health system perspective. Methods: we estimated costs for screening, diagnostics, and treatment. We conducted a cross-sectional study in seven regions with primary data collected from 50 health facilities. Data collection included structured questionnaires, with secondary data from the Ministry of Health and other sources. A mixed-methods approach combined ingredients-based costing and financial expenditures to estimate direct medical and non-medical costs. All costs are reported in 2019 USD. Results: average costs were $3.71 for visual inspection with acetic acid, $16.49 for Pap smear, and $46.65 for human papillomavirus deoxyribonucleic acid (HPV DNA) testing. Screening cost drivers were clinical exam supplies and clinical equipment for visual inspection with acetic acid, offsite processing of specimens for Pap smear, and lab equipment costs for HPV DNA procedure. The average cost of diagnosis via colposcopy alone was $25.73, and colposcopy with biopsy/endocervical curettage was $74.96. The average cost of treatment followed by one visit for pre-cancerous lesions was $195.24 for loop electrosurgical excision, $47.35 for cryotherapy, and $32.35 for thermal ablation. Clinical equipment and lab costs were the largest contributors to colposcopy and endocervical curettage/biopsy expenses. Clinical equipment made up the largest portion of cryotherapy, loop electrosurgical excision, and thermoablation costs. Conclusion: this study is the first to estimate the costs of HPV screening and treatment in Senegal, which can be used to inform decision-making on cervical cancer investments.

Socioeconomic inequalities in human papillomavirus knowledge and vaccine uptake: evidence from a cross-sectional study in China.

Objective: Providing the human papillomavirus (HPV) vaccine is effective to eliminate the disparity in HPV-related cancers. It is unknown regarding inequality in the distribution of HPV vaccination in China since the vaccine was licensed and approved for use in 2016. This study aimed to examine socioeconomic inequalities in HPV-related knowledge and vaccination and identified factors associated with such inequalities. Methods: Self-administered questionnaires measuring HPV-related knowledge and vaccine uptake were completed by 1,306 women through online survey platform. HPV knowledge was assessed using a 12-item question stem that covered the hazards of HPV infection, HPV vaccine dosage, benefits, and protection. Cluster analysis by combining monthly household income, educational level, and employment status was used to identify socioeconomic status (SES) class. The concentration index (CI) was employed as a measure of socioeconomic inequalities in HPV-related knowledge and vaccination. Linear regression and logistic regression were established to decompose the contributions of associated factors to the observed inequalities. Results: The CI for HPV-related knowledge and vaccine uptake was 0.0442 and 0.1485, respectively, indicating the higher knowledge and vaccination rate were concentrated in groups with high SES. Education and household income made the largest contribution to these inequalities. Age, residency and cervical cancer screening were also important contributors of observed inequalities. Conclusion: Socioeconomic inequalities in HPV-related knowledge and vaccination uptake are evident in China. Interventions to diffuse HPV-related information for disadvantaged groups are helpful to reduce these inequalities. Providing low or no-cost HPV vaccination and ensuring accessibility of vaccines in rural areas are also considered to be beneficial.

Potential Transcript-Based Biomarkers Predicting Clinical Outcomes of HPV-Positive Head and Neck Squamous Cell Carcinoma Patients.

Human papillomavirus (HPV)-positive Head and Neck Squamous Cell Carcinomas (HNSCC) comprise a particular cancer entity traditionally associated with better clinical outcomes. Around 25% of HNSCC are HPV positive, HPV16 being the most prevalent type. Nevertheless, close to 30% of the HPV-positive patients have an unfavorable prognosis, revealing that this type of tumor exhibits great heterogeneity leading to different clinical behaviors. Efforts have been made to identify RNA molecules with prognostic value associated with the clinical outcome of patients with HPV-positive HNSCC, with the aim of identifying patients at high risk of metastasis, disease recurrence, and poor survival, who would require closer clinical follow-up and timely intervention. Moreover, the molecular identification of those HPV-positive HNSCC patients with good prognosis will allow the implementation of de-escalating therapeutic strategies, aiming to reduce side effects, resulting in a better quality of life. This review compiles a series of recent studies addressing different methodological and conceptual approaches aimed at searching for potential gene expression-based biomarkers associated with the prognosis of patients with HPV-positive HNSCC.

HPV Detection in Breast Tumors and Associated Risk Factors in Northeastern Brazil.

Breast cancer risk factors include lifestyle, genetic-hormonal influences, and viral infections. Human papillomavirus (HPV), known primarily as the etiological agent of cervical cancer, also appears active in breast carcinogenesis, as evidenced in our study of 56 patients from northeastern Brazil. We assessed the clinical and sociodemographic characteristics, correlating them with various breast cancer tumor types. HPV detection involved amplifying the L1 region, with viral load measured using the E2/E6 ratio and viral activity indicated by E5 oncogene expression. Predominantly, patients over 56 years of age with healthy lifestyles showed a high incidence of invasive ductal carcinoma and triple-negative breast cancer. HPV was detected in 35.7% of cases, mostly HPV16, which is associated with high viral loads (80 copies per cell) and significant E5 expression. These results hint at a possible link between HPV and breast carcinogenesis, necessitating further studies to explore this association and the underlying viral mechanisms.

Association between dietary folate intake and HPV infection: NHANES 2005-2016.

BACKGROUND: Recent studies have established a correlation between folate levels and the incidence of cervical cancer. Given that Human Papillomavirus (HPV) infection is a primary etiological factor in the development of cervical cancer, the nature of the relationship between dietary folate intake and HPV infection remains an area of ongoing investigation. METHODS: To investigate the association between dietary folate intake and HPV infection, this study utilized data from the National Health and Nutrition Examination Survey (NHANES) spanning from 2005 to 2016. Multivariate logistic regression analysis was employed to examine the potential associations. Furthermore, the use of restricted cubic splines (RCS) facilitated the exploration of any non-linear correlations. Additionally, subgroup analyses were used to explore this correlation in different populations. RESULTS: The study encompassed a total of 6747 women aged between 18 and 59 years. For every one mcg increase in folate intake, the incidence of HPV infection is reduced by 1% (OR = 0.99, p<0.05). Besides, folate intake was categorized into quartiles as follows: Q1 (<211 mcg/day), Q2 (211-311 mcg/day), Q3 (311-448 mcg/day), and Q4 (>448 mcg/day). The adjusted odds ratios (OR) for the different folate levels were as follows: Q2: 0.94 (95% CI: 0.76-1.16), Q3: 0.84 (95% CI: 0.67-1.04), and Q4: 0.63 (95% CI: 0.49-0.81). The RCS analysis confirmed a nonlinear relationship between dietary folate intake and HPV infection risk. Notably, a significant inverse association was observed when dietary folate intake exceeded 193.847 mcg/day. CONCLUSIONS: In conclusion, the findings of this study indicate a negative association between dietary folate intake and the risk of HPV infection. This association demonstrates a nonlinear pattern, particularly evident at higher levels of folate consumption.

Clinico-histopathological and molecular detection of small ruminants' papillomaviruses in Iran.

BACKGROUND: Papilloma DNA viruses are one of the viruses that cause skin lesions in ruminants. OBJECTIVES: The clinical, histopathological and molecular characteristics of cutaneous papilloma in ruminants in Iran are to be investigated in this study. METHODS: Samples were collected from 19 small ruminants (5 sheep and 14 goats) with various papillomatosis lesions. The samples taken were studied with histopathological and molecular techniques. RESULTS: In clinical terms, the lesions appeared in different sizes, ranging from 0.5 to 11 cm, and the cauliflower exophytic masses appeared in other parts of the animal's body. In the limbs, most papilloma lesions have been seen (42.1%). In histopathological examination, perinuclear vacuolation epidermal granule layer with various degrees of hypergranulosis, hyperkeratosis, acanthosis, orthokeratosis and parakeratosis were seen. Moreover, all the suspected samples were positive for papillomavirus using the polymerase chain reaction technique. CONCLUSIONS: Although the prevalence of papillomaviruses in Iranian sheep and goats is low, it seems necessary to distinguish them from other viral skin diseases, such as cutaneous contagious ecthyma, using molecular techniques and histopathology.

Sexually transmitted infections among active component members of the U.S. Armed Forces, 2015-2023.

This report summarizes incidence rates and trends of sexually transmitted infections (STIs) from 2015 through 2023 among active component service members of the U.S. Armed Forces. The data compiled for this report are derived from the medical surveillance of chlamydia, gonorrhea, and syphilis as nationally notifiable diseases. Case data for 2 additional STIs, human papilloma virus (HPV) and genital herpes simplex virus (HSV), are also presented. The crude total case rates of chlamydia and gonorrhea initially rose by an average of 6.7% and 9.8% per year, respectively, until 2019. From 2020 onwards, rates steadily declined. By 2023, chlamydia rates had dropped by approximately 39%, while gonorrhea rates had fallen by more than 40% for female, and 19% for male, service members. Initially syphilis increased, on average, 10% annually from 2015 to 2019, then declined in 2020, but resumed its upward trend through 2023, nearly doubling the 2015 rate in 2023. The total crude annual incidence rates of genital HPV and HSV exhibited downward trends in general over the surveillance period, decreasing by 30.7% and 24.7%, respectively. Age- and gender-adjusted case rates for chlamydia, gonorrhea, and syphilis remain elevated within the U.S. Armed Forces compared to the general U.S. population, which may be due to factors that include mandatory STI screening, more complete reporting, incomplete adjustment for age distribution, and inequitable comparisons between the military active duty and general U.S. populations. Social restrictions enacted during the COVID-19 pandemic may have contributed to declines in true case rates and screening coverage.

Human Papillomavirus Vaccination by Birth Fiscal Year in Japan.

Importance: The Ministry of Health, Labour, and Welfare (MHLW) of Japan aggregates human papillomavirus (HPV) vaccination data across Japan for each fiscal year (FY) by age at vaccination. Birth FY (BFY)-specific vaccination coverage remains unknown. Objective: To calculate the BFY-specific vaccination coverage for each FY and the cumulative first-dose coverage for each BFY in Japan, to understand the generation-specific vaccination coverage, and to estimate the cumulative first-dose coverage of each BFY that would be achieved by FY 2028 vs World Health Organization (WHO) targets. Design, Setting, and Participants: In this cross-sectional study, MHLW-published national age-specific HPV vaccination numbers and demographic data for female individuals were used to calculate the BFY-specific first-dose coverage for each FY and the BFY-specific cumulative first-dose coverage. It was assumed that the BFYs 2007 to 2012 vaccination coverage in FY 2023 to 2028 would remain the same as the vaccination coverage of the same grade in FY 2022 to estimate the cumulative first-dose coverage that would be achieved by FY 2028. Data analysis was performed from December 2023 to January 2024. Exposure: Two MHLW policy changes were the government's suspension of proactive recommendation for HPV vaccination in June 2013 and the government's resumption of proactive recommendation for HPV vaccination in April 2022. Main Outcomes and Measures: The primary outcome was generation-specific vaccination coverage among female individuals born in BFYs 1994 to 2010 in FYs 2010 to 2022, calculated using reconfigured published data. Results: In this study of vaccination data for 9 414 620 female individuals, the generation-specific vaccination coverage was 71.96% for the vaccination generation (BFYs 1994-1999), 4.62% for the vaccine-suspension generation (BFYs 2000-2003), 16.16% for the generation that received information individually (BFYs 2004-2009), and 2.83% for the vaccine-resumed generation (BFY 2010). HPV routine vaccination coverage was extremely low in BFYs 2000 to 2010 (0.84%-25.21%) vs BFYs 1994 to 1999 (53.31%-79.47%). The cumulative first-dose coverage that was estimated to be achieved in the vaccine-resumed generation by FY 2028 plateaued at 43.16%. Conclusions and Relevance: Even after the resumption of MHLW's proactive recommendations, HPV vaccination coverage has only minimally recovered in Japan. The cumulative first-dose coverage that was estimated to be achieved in the vaccine-resumed generation by FY 2028 is below the WHO target. These findings reveal that stronger cervical cancer control measures are required, particularly for the vaccine-resumed generation, which will plateau at approximately one-half the WHO target values.