Perianal fistulizing Crohn's disease is the main risk factor for anal cancer in patients with inflammatory bowel disease. Whether this occurs due to a higher frequency of human papillomavirus remains unclear. The authors aimed to evaluate the prevalence of HPV and high-risk HPV in patients with perianal Crohn's disease, compared with a control group.The authors conducted a two-center cross-sectional study in which perianal fistulizing Crohn's disease patients were matched for age and sex with patients with anorectal fistula without Crohn's disease. Biopsy specimens were obtained from fistulous tracts during examination under anesthesia for both groups. The samples were sent for HPV detection and genotyping using the INNO-LiPA test.A total of 108 subjects (54 in each group) were recruited. The perianal fistulizing Crohn's disease group showed a statistically higher frequency of HPV in the fistulous tract than the control group . Separate analyses on high-risk types demonstrated that there was a numerically higher frequency of HPV in the perianal fistulizing Crohn's disease group. In multiple logistic regression, patients with perianal fistulizing Crohn's disease were found to have a chance of HPV 3.29 times higher than patients without Crohn's disease , regardless of other variables. The types most frequently identified in the perianal fistulizing Crohn's disease group were HPV 11 (12.96%) and HPV 16 (9.26%).Perianal fistulizing Crohn's disease is associated with a higher prevalence of HPV than in patients with anorectal fistula without Crohn's disease. Perianal Fistulizing Crohn's Disease (PFCD) is a disabling complication present in 23% to 38% of patients with Crohn's Disease (CD) and is considered to be an independent factor for poor prognosis ,2. OptimHPV is a small non-enveloped DNA virus with icosahedral symmetry ,9. CertaPFCD is the main risk factor for the development of anal squamous cell carcinoma in inflammatory bowel diseases ,14. It iThis was a two-center cross-sectional study that was developed at Hospital das Clínicas, University of São Paulo Medical School, and Heliópolis Hospital. These two institutions are referral centers for treating PFCD in the city of São Paulo, Brazil. The authors follow the STROBE Statement to guide the present study's manuscript.The patients in the PFCD group were recruited between December 2018 and November 2020 at the inflammatory bowel disease outpatient clinic, after being electively indicated for seton or fistulotomy procedures. The control group consisted of patients with perianal fistula without CD who were selected at the general coloproctology outpatient clinic. The following patients were excluded from the study: under-eighteens; pregnant women; Human Immunodeficiency Virus (HIV)-positive individuals; patients presenting immunosuppression due to other pathological conditions or medications; patients with transplants; patients with previous histories of radiotherapy or surgical treatment for SCC; patients with a previous or current history of anogenital HPV; patients undergoing HPV vaccination schemes; patients who did not agree to participate in the study; and those who did not sign the free and informed consent statement. This project was approved by the Ethics Committee for the Analysis of Research Projects (CAPPesq) and Ethics Committee of Heliopolis Hospital on 11/07/2018, with a Certificate of Presentation for Ethical Assessment 00265418.0.0000.0068.Data collection took place in three steps and was performed by a single physician. The first step consisted of an interview, to obtain the patients’ clinical characteristics. The second step consisted of a review of the medical records to confirm the diagnosis and staging of Crohn's disease. The third step consisted of filling out a printed questionnaire by the patient addressing sexual behavior.To determine the sample size, the prevalence of anal HPV in the general population was considered to be around 5% The sample size obtained was 110 patients, with 55 individuals in each group, considering a loss/refusal potential of greater than 10%, with a statistical significance level of 5% and test power of 80%.The material analyzed was obtained during the surgical procedure for treating perianal fistula (fistulotomy or seton placement). The external orifice and/or path of the fistula was biopsied and sent for analysis . The mat®, Belgium) was used.Detection of the virus and genotyping was performed using the INNO-LiPA™ HPV genotyping extra kit (Fujirebio©), which can identify 32 types of HPV by means of a PCR reaction followed by reverse hybridization, as described below. Part of the L1 region of the HPV genome was amplified by means of PCR using biotinylated SPF10 (65 bp) primers, and using the human HLA-DPB1 gene, as quality control for the samples. This assay allows simultaneous and independent detection of 13 high-risk HPV genotypes , six of probable high-risk , nine of low risk  and four that are not classified regarding risk . All the manufacturer's instructions were followed for testing. For HPV genotyping, the automated equipment AutoLipa48® . The quantitative characteristics were described according to groups, using summary measurements , and were compared between groups using the Student t test or the Mann-Whitney test.The presence of HPV was described in accordance with the characteristics that have been shown to be related to HPV in the literature. Associations of qualitative characteristics with the presence of HPV were verified using chi-square tests or exact tests. The quantitative characteristics were compared according to the presence of HPV by using the Student p < 0.20) and with clinical relevance for explaining the presence of HPV in patients, and all variables were maintained in the final model (full model).Unadjusted Odds Ratios (OR) were estimated for each characteristic evaluated for the chances of occurrence of HPV, using bivariate logistic regression and estimated multiple logistic regression models. The authors selected the variables that in the bivariate tests presented significance levels lower than 0.20 : 55 patients in the PFCD group and 55 patients in the control group. One patient in the PFCD group was excluded because it was found that he had previously undergone treatment for a condylomatous lesion, and one patient in the control group was excluded because he received a confirmed HIV diagnosis just a few months after sample collection and would thus have been in the immunological window. Hence, 108 patients remained in the study for the final analysis, comprising 54 patients in each group.Among the demographic and behavioral characteristics evaluated, only schooling presented a statistically significant difference between the groups (p = 0.024), such that the patients with PFCD had higher levels of education than the patients in the control group . VariablRegarding the specific clinical characteristics of the PFCD group, the mean age was 35.5 years, 51.9% were female, and the time since receiving the diagnosis of the disease was a mean (SD) of 7.76 (6.58) years. A total of 90.7% of the patients were undergoing anti-TNF treatment at the time of sample collection; 7.4% were being treated with ustekinumab; 1.9% were being treated with vedolizumab; and 29.62% had previously been exposed to at least one biological therapy. Concomitant use of azathioprine was identified in 48.2% of the patients and only two patients were using corticosteroids. The vast majority (88.8%) of the patients presented colonic disease in association with perianal disease, 96.3% of the patients had a history of perianal surgery, with an average of 4.09 ± 3.6 operations per patient .Table 2SThrough analyzing the frequency of HPV and adding the variable PFCD into the analysis as a potential risk factor together with factors known to be influential such as the number of previous partners, previous STI, anal sex, age, gender, marital status, and smoking, it could be seen that only the presence of PFCD and the number of partners influenced the presence of HPV statistically (p = 0.046 and p = 0.006 respectively) .Table 4RWhen the authors translocated the factors with positive associations with HPV in a multiple logistic regression table , the autSpecific analysis on the HPV types showed that in the PFCD group, 18.5% presented at least one type of high-risk HPV, among which HPV 16 was the most frequent type (9.26%), 7.40% had potential high-risk HPV and 16.70% had low-risk HPV, among which HPV 11 was the most prevalent, identified in 12.96% of the patients with PFCD .Fig. 2PeThe present study demonstrated that PFCD is an independent factor for the higher prevalence of HPV in relation to a control group: One-third of the patients with PFCD (33.3%) presented HPV in the perianal fistulous tract and 18.5% of them had high-risk HPV. The frequency of high-risk HPV was approximately twice that found in the control group, but this difference was not statistically significant. A larger sample would be needed to assess whether the higher frequency of high-risk HPV becomes significant at the population level. Some studies have suggested that PFCD is the main risk factor for anal cancer in patients with IBD ,13,14. Hp < 0.001) HPV 16 and 18 are the main subtypes correlated with anal carcinogenesis and are responsible for 87% of anal cancer cases worldwide It is speculated that in chronic and systemic inflammatory states, the presence of complex perianal fistulas requiring multiple local procedures along with the use of immunomodulatory and/or immunosuppressive drugs may affect the defense mechanisms responsible for viral clearance, thereby promoting maintenance of HPV in fistulous pathways. Permanent high-risk HPV infection can initiate a carcinogenic cascade by preventing apoptosis of dysplastic cells, with consequent malignancy. The authors tried to minimize the differences between the groups by comparing the patients with PFCD with patients with anorectal fistula unrelated to CD. Thus, although perianal inflammation is generally higher in CD, both groups had anorectal fistulas.The potential role of biological therapy and immunosuppressive treatments on the prevalence of HPV in the IBD population is unknown. It has been demonstrated that chronic viral infections, such as varicella-zoster virus and hepatitis B virus can be reactivated with immunosuppression Diagnostic screening methods for identifying HPV and cytological alterations have been used since the 1960s. Anal brush cytology is the method most used, given its low cost and high feasibility Historically, patients with inflammatory bowel disease have been found to have higher schooling levels and greater purchasing power than the general population. The authors found higher schooling in the PFCD group than in the control group, in line with the literature Prophylactic vaccines have been shown to be effective in the primary prevention of HPV infection and its associated diseases ,28. HoweThe present study is associated with some limitations. Firstly, the cross-sectional design is methodologically unequipped to address any risk correlation between the higher frequency of HPV and the occurrence of anal cancer. Moreover, information regarding sexual behavior may be subject to information bias due to embarrassment. The authors tried to overcome this bias by handing the questionnaire while the patients were in the waiting room, in order to avoid oral questioning. Finally, the authors believe the small sample size of this study is a major limitation to further extrapolations of the authors’ findings.In our study, it can be concluded that the patients with perianal fistulizing Crohn's disease had a higher prevalence of HPV than patients with perianal fistulas without Crohn's disease. Further prospective studies are warranted to assess the long-term impact of HPV infection on the risk of anal cancer in PFCD patients.Boarini L.R. coordinated the study, he contributed to the conceptualization, project administration, and writing original draft. Sobrado CW was involved in the study conceptualization and supervision. Mota G.R. and Villa L.L. contributed in methodology and investigation. Albuquerque I.C. biopsied the fistulous tract during the surgical procedure and contributed to investigation. Queiroz N.S.F. contributed to writing review and editing the manuscript. Facanali C.B.G., Nadal S.R., and Cecconello were involved in the conception and writing review. All authors contributed to the critical revising and the final approval of the manuscript.The authors declare no conflicts of interest.


Only 8% of the participants reported a negative reaction from parents when talking about HPV vaccines. However, in practice, physicians very rarely recommend this vaccine. HPV vaccination was recommended more often by female physicians (p = 0.03), general practitioners (p < 0.001), physicians working over five years (p < 0.001), doctors who regularly vaccinated themselves against influenza (p = 0.01) and those who vaccinated their children against HPV (p =0.001). The availability of educational materials for parents and/or patients encouraged physicians to provide this information (p < 0.001). Polish gynecologists and general practitioners declared a positive attitude regarding HPV vaccines; however, they rarely recommended this vaccine. Physicians who vaccinate themselves against influenza and their own children against HPV are more likely to provide information and encourage HPV vaccination in others. Additionally, the availability of educational material for parents and adolescents plays an essential role in the popularization of this vaccination. Knowledge alone is not enough for physicians to recommend the vaccination to patients.Human papillomavirus (HPV) leads to diseases of the skin and mucous membranes of the anogenital and upper gastrointestinal tract, especially neoplasia. HPV vaccinations effectively protect against the development of HPV-related diseases. However, despite the wide availability of vaccination for patients, only a few percent of Polish children are vaccinated. The reasons for this are certainly complex. Therefore, the aim of the study was to evaluate gynecologists’ and general practitioners’ knowledge, awareness and attitudes towards HPV vaccination and analyze their opinions about the interest in HPV vaccinations among children and parents. An anonymous, voluntary, cross-sectional survey study was conducted among 300 Polish gynecologists and general practitioners. Participants were from a diverse group with a wide range of work experience and different workplaces. Most of the respondents (83%), especially the gynecologists ( Human papillomavirus (HPV) infection is perceived as the most common sexually transmitted infection and it plays a crucial role in the formation of various neoplasm in women and men ,2. DiagnThe introduction of HPV vaccines has allowed for a successful decrease in the rate of HPV infections and HPV-related diseases . AlthougStreptococcus pneumoniae (56%) and 105,603 against Rotavirus—around 25% of the targeted children’s population [According to the United Nations International Children’s Emergency Fund (UNICEF) data, in Poland, only 22,342 boys and girls were vaccinated against HPV in 2018 (about 5% of the target population) [pulation . The reapulation ,12. AlsoThe annual incidences of cervical cancer are 19.8 cases per 100,000 women in Poland, 8.43/100,000 in Austria, 8.99/100,000 in the Netherlands, 10/100,000 in France and 7.62/100,000 in Cyprus . This maOne of the most important factors in popularizing HPV vaccination is the awareness and commitment of physicians. Physicians speaking with parents play an important role in the decision to vaccinate against HPV . VictoryThe aim of the study was to evaluate GYNs’ and GPs’ knowledge, awareness and attitudes towards HPV vaccination and analyze their opinions about the interest in the HPV vaccinations among children and parents.This cross-sectional survey study was performed between February 2018 and December 2018. The research participants included 300 Polish GYNs and GPs working inhospitals and outpatient clinics in Warsaw, Tarnow, and physicians from different cities in Poland participating in national medical conferences in Warsaw who voluntarily agreed to complete an anonymous survey . The proTo achieve the research goals, the authors prepared a special questionnaire based on the literature review ,18,19,20® and Microsoft Excel®. Categorical data were presented as frequencies and percentages. In the study, we developed relationships in relation to awareness, knowledge, opinions about HPV of employees according to gender, place of work, and looked for other sources to account for the occurrence of certain views. To compare two groups of categorical variables, we used the chi-square test and we considered p values < 0.05 as statistically significant.Statistical analysis was performed with the use of Statsoft Statisticap < 0.0001). GPs more often provided this information on their own initiative than GYNs did (p < 0.001) and have a positive effect on the frequency of providing information about vaccinations by physicians . Most participants rate the level of parents and adolescents’ interest in HPV vaccination as poor . Less than one third of participants (27%) did not recommend HPV vaccines in their practice. As the reason for not recommending the HPV vaccine, the doctors indicated: lack of confirmation of vaccine effectiveness (16%), side effects (10%), high cost (10%) and being against vaccinations in general (1%). One in four respondents gave additional answers regarding not working with relevant groups of patients to recommend this vaccination.Over 70% of respondents reported recommending HPV vaccines to their patients. This is especially true for women physicians, GPs and workers in outpatient clinics witha longer tenure . The frep = 0.0001) and recommended this procedure . Almost half of the responders (47%) are vaccinated against seasonal influenza every year. These doctors more frequently spoke to patients about HPV vaccines and recommended them . Both GYNs and GPs are in favor of financial support for HPV vaccines . According to 28% of all participants, HPV vaccines should be compulsory and free of charge, for 47% the vaccine is recommended and co-financed by the Government, while for 25% of the population, the vaccine is recommended but not refunded. Compulsory status was more eagerly proposed by GPs than GYNs , respondents who were vaccinated against the flu  and those who work in a village or small town versus in a big city . Financial support was especially highlighted by GPs rather than the GYNs .Most respondents (75%) showed a positive attitude to vaccinate their own children, but the opinion on vaccination varied when considering the sex of the child . Doctorsp = 0.0008), possessing educational materials in the work place in comparison to those who do not have any , concerned with financial support for vaccines or not  and mandatory status or not  and having a positive attitude towards vaccinating their own children in comparison with those with a negative attitude .Only 42% of GYNs and 57% of GPs declared their cognizance concerning HPV vaccination as sufficient. Doctors indicated the most common sources of obtainingknowledge concerning HPV vaccination were the scientific materials and press , medical conferences , the internet , pharmaceutical companies , other doctors , university education , public media  and product data sheets or clinical trials .Most ofthe respondents were familiar with the high-risk groups of HPV infection, vaccination dose data and vaccination target, but they differed with the knowledge about vaccination protection . KnowledThe reasons for the differences in adolescent HPV vaccination coverage are complex and include issues of government policy, the organization of the health care system and physicians and parents’ attitudes ,21. The The Polish long-term National Oncological Strategy plans to vaccinate at least 60% of youth against HPV by 2028 . This isAccess to professional and accurate information is a challenge for both patients and doctors. A particularly strong correlation was revealed between the accessibility of educational materials for parents in medical facilities and the frequency of recommendations of HPV vaccination by physicians. Brochures and leaflets are perceived as additional to a doctor’s recommendation and an effective method of education, and have a positive influence on Polish parents in making decisions about their child’s immunization ,20.The study demonstrated that Polish physicians are quite knowledgeable about HPV infections and vaccines, but some of them have shortcomings. However, it is necessary to emphasize that medical professionals who have to deal with vaccinations should be much more educated and aware of the problems than patients. Perhaps because of this, the willingness of doctors to recommend HPV vaccination is unsatisfactory. Interestingly, physicians in other countries also sometimes show passivity in recommending this vaccination against HPV ,27. In tAlthough GYNs are not directly responsible for performing HPV vaccinations in Poland, this study showed that those specialists declared themselves as more eager to inform patients about the risks of HPV infection than general practitioners. They underscored the young patients’ interest in HPV vaccination more than GPs, which indicated their essential role in the introduction of this vaccination among youth. The low level of HPV vaccination among adolescents demonstrates the crucial role of parental education in this field. The leading role of GPs to promote this vaccination among parents was indicated in many previousstudies ,33,34. WAnother important aspect in promoting vaccination is years of service, which is associated with an increased willingness to recommend vaccinations. The rare recommendation of HPV vaccinations by young doctors indicates the shortcomings of university education, which are compensated for in postgraduate education and this needs to be changed. Physicians working in outpatient clinics have more opportunities to educate patients about disease prevention. General practitioners are more likely to talk to parents and know their views. Therefore, they are also more supportive of the option of mandatory HPV vaccination when inquiring what the vaccination status should be in Poland.In order to increase the encouragement of vaccination by doctors, it is necessary, first of all, to build the right personal conviction for vaccines among physicians. It is not so much the knowledge of the physicians that is important, but their personal beliefs . That isThe study has some limitations. It was conducted among a small population of well-educated physicians working mainly in two Polish regions. There are over 7000 GYNs and over 11,000 GPs in Poland. Therefore, it is more of a pilot study, although based on a randomly selected group in two towns. In the case of Warsaw, the participants constituted a smaller proportion of the whole, but in Tarnow, it was larger. The results are based on the physicians’ declarations and, despite the anonymous nature of this study, may be overstated. Some physicians may be hesitant to admit that they are not acting according to their knowledge and recommendations. The answers proposed in the survey did not cover all the options, but it is a consequence of the choice of simple closed questions. Voluntary participation in the survey may also create falsely inflated results, as those who are unsure of their competence or with negative attitudes to HPV vaccination may have deliberately refused to participate. Therefore, it is necessary to further analyze the awareness and attitudes of physicians in order to raise the level of HPV vaccination in Poland. This is additionally important because the public is positively disposed to vaccination, while there is inadequate awareness of the need ,35. The GYNs and GPs present satisfactory awareness and attitudes towards HPV vaccinations. However, they rarely recommend this vaccination to parents and patients. Therefore, the right motivation of doctors is needed. Their own positive attitude towards vaccinations is particularly important. Physicians who vaccinate their own children against HPV and vaccinate themselves against influenza are more likely to provide information and encourage vaccination in others. Additionally, the availability of educational material among parents and adolescents plays an essential role in the popularization of this vaccination. Knowledge alone is not enough for physicians to recommend vaccinations to patients. Time and determination are needed, resulting from the doctors’ profound belief in the need for HPV-related disease prevention.


HPV infection is closely related to the occurrence of cervical cancer and has an important adverse effect on human life and health. This study used data from the NHANES 2003–2016 to investigate the relationship between PIR and HPV infection status among Americans aged 20 and older.The data for this cross-sectional investigation came from the 2003–2016 National Health and Nutrition Examination Survey (NHANES), which included 9580 women who were 20 years of age or older. The linear and nonlinear correlations between PIR and the presence of HPV infection were investigated using multiple linear regression and smooth curve fitting. The stability of the relationship across groups was examined using subgroup analysis and interaction tests.There were 2232 impoverished homes and 2543 rich households among the 9580 adult participants aged 20 and above. PIR (ratio of income to poverty) was found to be significantly inversely related to the presence of HPV infection [0.91 ] after adjusting for all other covariates, and the trend persisted even after categorizing PIR into high- and low-income groups (PIR>4 and PIR<1). In addition, significant negative relationships were discovered in subgroup analyses for women aged 25 to 59 [0.90 ], non-Hispanic whites [0.80 ], non-diabetics [0.91 ], and those who had ever engaged in sex [0.91 ].PIR was highly and negatively correlated with the presence of HPV infection in American women aged 20 and older. The results of this study are of great significance for preventing HPV infection and improving the accuracy of HPV screening. The Based on statistics, there are 80 million HPV-positive individuals in the United States, and HPV oropharyngeal cancer is more prevalent than HPV cervical cancer . AccordiFamily income to poverty ratio (PIR) is closely related to the health of human life, and it has been claimed that PIR can affect children’s health, especially among low-income children in the U.S., confirming that higher family incomes are significantly correlated with lower child morbidity rates . In addiIn order to investigate the relationship between family income to poverty ratio and HPV infection status among American women aged 20 and older, we conducted cross-sectional research utilizing data from the NHANES 2003–2016.22.1The National Health and Nutrition Examination Study (NHANES) is a population-based, cross-sectional study used to gather data on the health and nutrition of Americans living in households. The study procedure was approved by the National Center for Health Statistics (NCHS) Research Ethics Review Board. All subjects gave their written consent at the time of recruiting. Statistics for this research came from the NHANES during 2003-2016. In this survey, we excluded 58424 participants with missing HPV infection status, 863 participants with missing PIR, 1025 participants under the age of 20 years, and 1166 participants with missing status for the remaining covariates. The study ultimately included 9580 participants. The workflow for choosing samples is shown in 2.2The PIR was the study’s exposure variable, while the outcome variable was the presence of HPV infection. We track the Consumer Price Index (CPI) based on family incomes and federally recognized levels of poverty to determine the relevant income index, PIR, which we divide into three classes: the poor (PIR<1), the middle class (PIR1-4), and the rich (PIR>4). HPV infection status was determined by genotyping DNA extracted from vaginal swabs, obtained by the Digene hybridization capture method and prototype line blot assay and Roche Linear Array.https://www.cdc.gov/nchs/nhanes), you may find explanations for all variables.Age, race, marital status, smoking, consumption of alcohol, sexual intercourse, diabetic status, and BMI were all covariates in this study. On the NHANES website’s official page (2.3R (version 4.1.3) and Empower Stats (version 2.0) were used for all analyses. Demographic characteristics of subjects were assessed by PIR categorization using a t-test and chi-square test. The linear association between PIR and HPV infection status was examined using multiple regression models. The nonlinear association between PIR and HPV infection status was examined using the weighted smoothed curve fitting approach and the generalized summation model. By using subgroup analysis and an interaction test, the connection between PIR and HPV infection status in various categories was investigated.33.1By PIR, the weighted features were divided into three groups: low-income, medium-income, and high-income. There were 9580 adult females above the age of 20, and the mean PIR for everyone who took part was 2.48 ± 1.67. The high-income group’s participants (PIR > 4) were older than the low-income group’s (PIR<1) participants. Adult females living below the poverty line had a higher likelihood of being Mexican American and non-Hispanic black and having higher BMI levels than adult females living in affluent households. Table 1.3.2The findings of multivariate linear regression analysis for all three models of the association between PIR and HPV infection status are presented in 3.3We discovered erratic correlations between PIR and HPV infection status in subgroup analyses stratified by age, race, diabetes, and sexual activity. As shown in 4In this research, we sought to define the relationship between PIR and HPV infection status in American women 20 years of age and older. Upon examination, we discovered a strong inverse relationship between PIR and the presence of HPV infection [0.91 ], and smoothed curve fitting revealed a non-linear negative association between the two. Age, race, diabetes, and sexual activity did not significantly depend on the adverse connection, according to subgroup analyses and interaction results.Previous research has shown that HPV is linked to several ailments, and a recent study called Estimating the Global Prevalence of Human Papillomavirus Infection in Pregnant Women found that young age with low levels of education, multiple lifelong partners, and young age with low levels of HIV infection were all associated with increased risk. Pregnant women also had a significantly higher prevalence of pregnancy-related illnesses and HIV than the general population . MoreoveFurthermore, high-income nations adopt cytology-based screening techniques, which produce more accurate screening findings , 28. ScrThere are still shortcomings in our study, first of all, as it is a cross-sectional analysis, we are unable to discuss the causal link and the underlying mechanisms of effect, and secondly, the covariates included may not be completely accurate which can affect the accuracy of the results. However, there are some strengths in our study, such as the fact that It is founded on a great deal of representative data from NHANES, and the fact that we have demonstrated a non-linear negative association between PIR and HPV status, which has diagnostic value in predicting the presence of HPV in a patient.PIR was strongly and unfavorably related to the presence of HPV infection in American women aged 20 and older. Population variations in PIR should be taken into consideration during HPV diagnosis and therapy. PIR is anticipated to play a significant role in the population’s propensity to HPV infection. Improving the income level of patients and strengthening the screening of HPV in poverty-stricken areas may contribute to the prevention and treatment of cervical cancer. Future research is required to corroborate our findings.The datasets presented in this study can be found in online repositories. The names of the repository/repositories and accession number(s) can be found in the article/supplementary material.The studies involving humans were approved by NCHS Ethics Review Board (ERB) Approval. The studies were conducted in accordance with the local legislation and institutional requirements. Written informed consent for participation in this study was provided by the participants’ legal guardians/next of kin.YuaZ: Writing – original draft, Conceptualization, Data curation, Investigation, Methodology, Software, Writing – review & editing. JZ: Investigation, Writing – review & editing. RX: Data curation, Writing – review & editing. YuZ: Methodology, Writing – review & editing. YX: Conceptualization, Writing – review & editing. JM: Investigation, Writing – review & editing. CY: Investigation, Writing – review & editing. YS: Funding acquisition, Resources, Supervision, Writing – review & editing.


Estimated hepatitis C prevalence within the Veterans Health Administration is higher than the general population and is a risk factor for advanced liver disease and its associated complications. We describe the hepatitis C care continuum within the Veterans Health Administration between January 1, 2014 and December 31, 2022.Individuals in Veterans Health Administration care 2021-2022 who were eligible for direct-acting antiviral treatment between January 1, 2014 and December 31, 2022 comprised our cohort. We evaluated the proportion of Veterans who progressed through each step of the hepatitis C care continuum, and identified factors associated with initiating direct-acting antivirals, achieving sustained virologic response, and repeat hepatitis C viremia after achieving sustained virologic response.We identified 133,732 Veterans with hepatitis C viremia during our study timeframe. Hepatitis C treatment was initiated in 107,134 (80.1%), with sustained virologic response achieved in 98,136 (91.6%). In those who achieved sustained virologic response, 1,097 (1.1%) had subsequent repeat viremia and 579 (52.8%) were retreated for hepatitis C. Veterans of younger ages were less likely to initiate treatment and achieve sustained virologic response, and more likely to have repeat viremia. Stimulant use and unstable housing were negatively associated with each step of the hepatitis C care continuum.The Veterans Health Administration has treated 80% of Veterans with hepatitis C with direct-acting antiviral therapy since its approval in 2014 and achieved sustained virologic response in more than 90% of those treated. Repeat viremia is rare and is associated with younger age, unstable housing, opioid use, and stimulant use. Ongoing efforts are needed to reach younger Veterans, and Veterans with unstable housing or substance use disorders.All Authors: No reported disclosures


To investigate the infection status of high-risk human papillomavirus (HR-HPV) E6/E7 mRNA in patients with a cytological diagnosis of “atypical squamous cells of undetermined significance” (ASCUS) and to analyze the pathogenic rate of different high-risk HPV subtypes combined with biopsy pathological results to provide a more accurate basis for managing ASCUS patients.A total of 1387 patients with ASCUS and HPV E6/E7 mRNA positivity who were referred for colposcopy were retrospectively analyzed. They were divided into HPV16+, 18/45 + and other HR-HPV + groups premenopausal and postmenopausal groups. The pathological results of the biopsy were divided into the LSIL- group  and the HSIL + group . SPSS was used for the analysis.The age group 31–40 years had the highest level of HPV16+, and HPV18/45 + was the highest in the 41–50 years group. The detection rates of HSIL + in the HPV16+, HPV18/45+, HPV 16/18/45 + and Other HR-HPV + groups were 48.4%, 18.8%, 43.9% and 15.0%, respectively. The infection rates of HPV16/18/45 in postmenopausal and premenopausal women were 42.4% and 34.3%, respectively. In the HPV18/45 group, the incidence of HSIL + was 30.0% in postmenopausal women and 15.0% in premenopausal women (P < 0.01). In the HPV 16 + and Other HR-HPV + groups, the incidence of HSIL + in postmenopausal patients was not significantly different from that in premenopausal patients. The incidence of cervical cancer in postmenopausal patients is significantly higher than that in premenopausal patients.Colposcopy referral or further biopsy is recommended for all ASCUS patients with HPV16/18/45E6/E7 mRNA positivity and postmenopausal patients with HR-HPVE6/E7 mRNA positivity. For premenopausal ASCUS patients with other HR-HPV E6/E7 mRNA positivity, colposcopy should be performed if possible, depending on the specific situation, to achieve early detection and diagnosis. Cervical cancer is one of the most common malignant tumors in women. There are approximately 100,000 new cases of cervical cancer in China every year . With thPersistent infection with high-risk human papillomavirus (HR-HPV) is the main cause of cervical cancer . Among tStudies have reported that 20% of all new cases of cervical cancer occur in women aged 65 and above, who account for 34% of cervical cancer deaths . For posA total of 6342 patients who were diagnosed with “atypical squamous cells-unclear meaning” (ASC-US) in the affiliated Hospital of Jining Medical College from January 2017 to December 2021 were selected. A total of 1387 patients (21.9%) with positive HPV E6 /E7 mRNA screening and cervical biopsy were enrolled in this retrospective study.The exclusion criteria were as follows: (1) pregnant and lactating women; (2) previous diagnosis of cervical cancer or other malignant tumors; and (3) unsatisfactory cytological results. The age of the patients ranged from 16 to 77 years old, with an average age of 40.80 ± 11.32 years. The patients positive for the HPV16 or 18/45 subtypes were classified as the HPV16/18/45 subtype positive group, and those negative for the 16 and 18/45 subtypes but positive for another high-risk subtype were classified as the other high-risk subtype positive group (Other HR-HPV+). See Fig. The exfoliated cells of the cervical canal and external orifice of the cervix were collected with a special brush designed for liquid-based cell tests (TCT). The specimens were made with a Liqun technology centrifuge and stained with Pap. Two professional pathologists made the cytological diagnosis. According to the TBS (2004) classification criteria, the TCT results were described as follows: no intraepithelial lesions or malignant lesions (NILM); atypical squamous cells-no clear meaning (ASCUS); low-grade squamous intraepithelial lesions (LSIL); atypical squamous cells without excluding high-grade intraepithelial lesions (ASC-H); high-grade squamous intraepithelial lesions (HSIL).Fourteen high-risk HPV E6/E7 mRNA types, including HPV 16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 66 and 68, could be qualitatively detected by using the Hologic Panther automatic molecular detection platform. According to the specific steps of the Aptima HPV test kit (capture hybridization), the preservation solution of 1 ml cervical exfoliated cells was absorbed into the sample delivery medium (STM). Finally, the result was determined by the ratio of the signal to the threshold (s/C0). The HPV E6/E7 mRNA-positive cases were further typed and identified according to the Aptima HPV 16, 18/45 genotype detection kit (capture hybridization). This method could detect HPV 16 and HPV18/45 E6/E7 mRNA but could not distinguish between HPV18 and HPV45.A professional vaginoscope physician used an electronic colposcopy system  to selectively take multiple biopsies in the acetic acid white test and iodine test abnormal areas. If there was no obvious abnormality, cervical biopsies were performed at 3, 6, 9 and 12:00, and cervical canal curettage (ECC) was performed if necessary. The biopsy tissue was fixed and preserved in 4% neutral formalin, and the routine paraffin sections were diagnosed by 2 professional pathologists. The pathological grades included the following: (1) Changes in the normal or chronic inflammatory response; (2) Low-grade squamous intraepithelial lesion (LSIL); (3) High-grade squamous intraepithelial lesion (HSIL); (4) Invasive carcinoma of the cervix (Ca); LSIL and lower lesions referred to as LSIL-, HSIL and higher lesions referred to as HSIL+, including HSIL and invasive cancer.The data were statistically analyzed by SPSS 26.0 software. The categorical data are expressed as the rate or percentage, the age is expressed as the mean ± standard deviation (x ± s), and the proportions in each group were compared by the chi-square test. The difference was statistically significant if P < 0.05.A total of 1387 cases were diagnosed as ASCUS and HPV E6/E7 mRNA positive by cytological screening. The positive rate for HPV16 was 30.1%, and the positive rate for HPV18/45 was 5.0%,The difference was statistically significant (P < 0.01). After grouping by age, the positive rate of HPV16 was significantly higher than HPV18/45 in all age groups. The positive rate of the HPV16/18/45 genotypes (35.9%) was significantly lower than that of the other HR-HPV genotypes (64.1%) (P < 0.01). Except for the > 60-year-old group, the positive rate of the HPV16/18/45 genotypes was significantly lower than that of the other HR-HPV types in the other age groups. The 31–40 years old group had the highest rate of HPV E6/E7+ (30.5%), followed by the 41–50 years old group 28.8%). The 31–40 years old group, followed by the 41–50 years old group, had the highest rate of HPV16+. The 41–50 years old group, followed by the ≤ 30 years old group, had the highest rate of HPV18/45+. See Fig. 8.8%. TheIn the HPV16/18/45 + group, the biopsy results were normal in 137 cases (27.5%), which was significantly lower than that in the Other HR-HPV + group (48.4%), and the difference was statistically significant (P < 0.01); that is, the morbidity of HPV16/18/45 was significantly higher than that of the Other HR-HPV subtypes.In the HPV16/18/45 + group, HSIL + was found in 219 cases (43.6%), which was significantly higher than that in the Other HR-HPV + group (15%), P < 0.01. That is, the morbidity of cervical HSIL + caused by subtypes of HPV16/18/45 was significantly higher than that of other subtypes of HR-HPV. See Table The percentage of patients with normal biopsy results in the HPV16 + group 25.2%) was significantly lower than that in the HPV18/45 + group (38.8%). The difference was statistically significant (P < 0.01); that is, the morbidity of the HPV16 subtype was significantly higher than that of the HPV18/45 subtype. The proportion of HSIL + in the HPV16 + group (48.4%) was significantly higher than that in the HPV18/45 + group (18.8%) (P < 0.01). The morbidity of cervical HSIL + caused by the HPV16 subtype was significantly higher than that of the HPV18/45. See Table 5.2% was The proportion of HSIL + in the HPV16/18/45 group was 42.3% before menopause and 49.6% after menopause, and the difference was not statistically significant (P = 0.163). In the Other HR-HPV group, the proportion of HSIL + was 14.2% before menopause and 18.3% after menopause, and the difference was not statistically significant (P = 0.201). That is, there was no significant difference in the morbidity of HSIL + between premenopausal and postmenopausal patients caused by HPV16/18/45, and so was Other HR-HPV.There were 17 cases of cervical cancer in the premenopausal HPV16/18/45 group (4.5%), which was significantly lower than the 26 cases of cervical cancer in the postmenopausal HPV16/18/45 group (22.2%) (P < 0.01). That is, the morbidity of cervical cancer in postmenopausal patients with HPV16/18/45 was significantly higher than that in premenopausal patients. Cervical cancer occurred in 12 cases (1.6%) in the premenopausal Other HR-HPV + group and 9 cases (5.7%) in the postmenopausal Other HR-HPV + group (P < 0.01); that is, the morbidity of cervical cancer in postmenopausal patients with Other HR-HPV was significantly higher than that in premenopausal patients. See Table The proportion of HSIL + in the HPV16 group was 46.8% in the premenopausal group and 53.5% in the postmenopausal group (P = 0.241). There was no significant difference in HSIL + morbidity between premenopausal and postmenopausal patients with HPV16. The proportion of HSIL + in the premenopausal HPV18/45 group  was significantly lower than that in the postmenopausal HPV18/45 group , and the difference was statistically significant (P < 0.01). That is, the morbidity of HSIL + caused by HPV18/45 in postmenopausal patients was significantly higher than that in premenopausal patients. See Table In recent years, the onset age of cervical cancer has tended to be younger, so early detection, early diagnosis and early treatment are more important for improving the prognosis of patients. Epidemiological data show that the highest incidence age of cervical cancer in situ is 30–35 years old and that of invasive cancer is 45–55 years old, and its incidence tends to be younger than in the past . The ageIt has been reported that most CIN2 lesions, especially in young women (< 30 years old), disappear spontaneously . TherefoRen et al.  found thWith regard to HR-HPV genotyping, some studies have shown that in patients with simple HPV positivity, the detection rate of HSIL + in HPV16/18-positive patients is significantly higher than that in other high-risk-positive patients , so the Moreover, undergoing colposcopy is not harmful, and the impression of colposcopy may help to increase the detection rate of high-level lesions compared with the psychological burden on patients. In cases of good communication by clinicians, the importance of avoiding missed diagnoses of high-level lesions is self-evident. It has been reported that for patients with simple HR-HPV infection, a treatment model based on risk stratification is feasible, and random biopsies are of little significance for patients with no abnormalities on colposcopy . TherefoIn addition, the high proportion of ASCUS in the diagnosis of TCT is partly due to the difference between postmenopausal and premenopausal patients. In postmenopausal women, due to changes in hormone levels and cervical atrophy, the junction of the squamous epithelium and columnar epithelium returns to the cervical canal , and theStudies have shown that the percentage of HSIL detected by cervical curettage in postmenopausal patients (9.9%) is higher than that in premenopausal patients (2.6%) . CombineThe percentage of HSIL + biopsies was 42.3% in the premenopausal HPV16/18/45 group and 49.6% in the postmenopausal HPV16/18/45 group; that is, there was no significant difference in the HSIL + morbidity of HPV16/18/45 between premenopausal and postmenopausal patients; at the same time, Other HR-HPV had no significant difference in HSIL + morbidity between premenopausal and postmenopausal patients. Then, the difference between premenopausal and postmenopausal morbidity caused by HPV16 and HPV18/45 was analyzed in detail: the proportion of HSIL + in the premenopausal HPV16 group was not significantly different from that in the postmenopausal HPV16 group. That is, there was no significant difference in high-grade morbidity between premenopausal and postmenopausal patients with HPV16. The proportion of HSIL + in the premenopausal HPV18/45 group was significantly lower than that in the postmenopausal HPV18/45 group, and the difference was statistically significant; that is, the high-grade morbidity of HPV18/45 in postmenopausal patients was significantly higher than that in premenopausal patients. Therefore, except for HPV18/45, there was no significant difference in the high-grade morbidity of HR-HPV between premenopausal and postmenopausal patients.Combined with the above conclusions of this study, we can explain some of the reasons why the HSIL + incidence of postmenopausal patients is higher than that of premenopausal patients: (1) The high-grade morbidity of HPV16/18/45 was significantly higher than that of Other HR-HPV, (2) At the same time, the infection rate of HPV16/18/45 in postmenopausal patients was higher than that in premenopausal patients. (3) The high-grade morbidity of HPV18/45 in postmenopausal patients was significantly higher than that in premenopausal patients. Some studies have found that the older the age of acquiring an HPV infection, the higher the degree of cervical lesions , which iIn the CastanonA literature , the incIt is mentioned in the literature that the incidence of cervical cancer in postmenopausal women is increasing, which may be due to the decrease in immune function in postmenopausal women , but it Conclusions: In summary, this study suggests that colposcopy referrals and biopsy diagnosis and treatment should be performed for all HPV16/18/45 E6/E7 mRNA-positive and postmenopausal HR-HPV E6/E7 mRNA-positive ASCUS patients, and premenopausal ASCUS patients with other HR-HPV E6/E7 mRNA positivity should also be examined by colposcopy if possible according to the specific conditions to achieve early detection, early diagnosis and early treatment. However, while 16 and 18 of the high-risk HPV subtypes were reported separately in this study, no specific reports were made on the other subtypes. The pathological changes of the cervical epithelium may also need to consider other factors, such as the number of pregnancies and deliveries and sexual history, which need to be further analyzed to provide a more comprehensive and specific basis for further standardized clinical treatment of ASCUS patients, provide effective data for the accurate diagnosis of ASCUS in pathology, and make a modest contribution to the maximum improvement of the prognosis of patients.


WHO has recommended HPV testing for cervical screening where it is practical and affordable. If used, it is important to both clarify and implement the clinical management of positive results. We estimated the performance in Lusaka, Zambia of a novel screening/triage approach combining HPV typing with visual assessment assisted by a deep-learning approach called automated visual evaluation (AVE).In this well-established cervical cancer screening program nested inside public sector primary care health facilities, experienced nurses examined women with high-quality digital cameras; the magnified illuminated images permit inspection of the surface morphology of the cervix and expert telemedicine quality assurance. Emphasizing sensitive criteria to avoid missing precancer/cancer, ~ 25% of women screen positive, reflecting partly the high HIV prevalence. Visual screen-positive women are treated in the same visit by trained nurses using either ablation (~ 60%) or LLETZ excision, or referred for LLETZ or more extensive surgery as needed. We added research elements  including collection of HPV specimens for testing and typing with BD Onclarity™ with a five channel output , and collection of triplicate cervical images with a Samsung Galaxy J8 smartphone camera™ that were analyzed using AVE, an AI-based algorithm pre-trained on a large NCI cervical image archive. The four HPV groups and three AVE classes were crossed to create a 12-level risk scale, ranking participants in order of predicted risk of precancer. We evaluated the risk scale and assessed how well it predicted the observed diagnosis of precancer/cancer.HPV type, AVE classification, and the 12-level risk scale all were strongly associated with degree of histologic outcome. The AVE classification showed good reproducibility between replicates, and added finer predictive accuracy to each HPV type group. Women living with HIV had higher prevalence of precancer/cancer; the HPV-AVE risk categories strongly predicted diagnostic findings in these women as well.These results support the theoretical efficacy of HPV-AVE-based risk estimation for cervical screening. If HPV testing can be made affordable, cost-effective and point of care, this risk-based approach could be one management option for HPV-positive women.The online version contains supplementary material available at 10.1186/s13027-023-00536-5. In the ongoing initiative to eliminate cervical cancer, the World Health Organization (WHO) highlights the central role of HPV . The recWhere HPV testing is done, a negative HPV result in mid-adulthood provides strong reassurance that cervical cancer/precancer is not present or imminent , 8. WhilAs a novel screen-triage-treat strategy, we are evaluating two complementary tests: HPV genotyping and artificial intelligence (AI)-assisted visual evaluation. Regarding HPV genotyping, there are approximately a dozen HPV types classified as carcinogenic, and the type of HPV strongly modifies risk of cancer, i.e., the risk groups in descending order of carcinogenicity are HPV16, then HPV18/45, then HPV31/33/35/52/58, then HPV39/51/56/59/68 . HPV typThe second complementary triage method is a visual adjunct called "automated visual evaluation (AVE)". AVE is a real-time, deep learning-based classifier of cervical appearance with a readout as either reflective of precancer/cancer, indeterminate, or normal based on images captured by a digital camera –15.The cross-combination of the four-level HPV type groups with the three-level AVE algorithm score creates 12 risk levels . Controls were women with completely visible squamocolumnar junctions (Type 1 or 2 Transformation Zones) whose visual screen was judged to be normal and not requiring referral for biopsy, combined with those that were referred but had histologic findings < CIN2.The results of the HPV testing performed in Lusaka were obtained by Onclarity batch testing for research purposes only, and unconnected to clinical management. Onclarity provides HPV typing that can approximate the type groups ranked in order of carcinogenicity . SpecifiThe AVE algorithm was pre-trained on the NCI cervical image bank that contains more than 150,000 images taken with Cerviscopes  or DSLR camera images taken by beam splitting of Zeiss colposcope images . The reaAn important aspect of the Zambian screening program is expert treatment of screen-positive women . If visuThe case and control histologic diagnoses in this study were based therefore on punch biopsies or LLETZ specimens, evaluated by an expert pathologist. As stated above, women that screened negative were also included as controls despite having no biopsy  given the very sensitive threshold for VIA positivity, high rates of referral, and the substantial expertise of the examining nurses.The population diagram for the study is shown in Fig. The data analysis included the following: First, we tested transfer learning of the candidate AVE algorithm for immediate use without modification on the J8 images. The J8 image type was a kind not previously included in AVE training. We postulated that portability might require retraining of the AVE algorithm to permit familiarity with the new image type. A small subset of images from women in the Zambian screening clinic was used for retraining, and contained 80 individuals with each classification . The retraining images were added incrementally  to the NCI core collection to consider incrementally how many of the previously unfamiliar kind of images were needed to transfer the algorithm successfully; 40 was the chosen number achieving reasonable performance , and precancer/cancer. In assessing reproducibility, the percent of the individuals that were extremely misclassified on replicates was of special interest .Accuracy of a test is typically judged to be the correct identification of cases and non-cases, generally assessed in a 2 × 2 table by sensitivity, specificity, and their tradeoff . However, in this version of AVE, a large "gray zone" of indeterminate results was established between precancer/cancer and normal. Thus, the analysis assessed a 3 × 3 matrix (which shows the three diagnostic truth classes as one dimension and three-level test classification as the other). The worst inaccuracies, i.e., the percent of extreme errors, were again of special interest .Shown in Table The initial "transfer learning" application of the pre-trained AVE algorithm to the Zambian J8 image set generated very poor performance, with nearly random discrimination of the reference diagnostic classes  individuals’ data from each ground truth class . Except for the experiment with only 17 + 3 individuals’ data addition, all other retrained algorithms performed well  ranked based on the HPV-AVE algorithm and compares what percent of the observed precancer/cancers (y-axis) in this population could be detected if a certain percent of the high-risk population is referred for management. In this figure, the HIV-positive population is demonstrated because there are more precancer/cancer outcomes permitting stratification of risk. In this example, one possible threshold or cutpoint for managing patients could be drawn at risks equal or greater than that observed for women that are HPV16+ and normal AVE. At this cutpoint, 92% of the expected precancers would be detected and treated. To achieve this sensitivity, 31% of the HIV-positive population would be referred for management.The data support that a combination of HPV typing and automated visual evaluation (AVE) could accurately distinguish women at different risks of cervical precancer/cancer. Current cervical cancer prevention guidelines in the US and Canada employ the principles of risk-based management , 24. AppAs one possible strategy, the screening process could start with collecting self-sampled vaginal swabs from the general screening population  and evalThe 12-level screening table would indicate each woman's chance of having precancer/cancer, and could be used by the decision-makers in the local public health and clinical authorities to create risk-action thresholds. In other words, those in charge of each setting could decide based on resources and risk tolerances how to convert the risks into actions, similar to how risks are used in current US and Canadian guidelines , 24.The strengths of this study include a large dataset of images from women with and without HIV, collection of HPV testing with genotyping, availability of multiple (triplicate) cervical images, and cervical disease outcomes on all patients. The nurses performing the standard of care VIA screening aided by digital camera imaging are highly trained, and have individually performed thousands of screenings, and often act as master-trainers for colleagues across the country and region. Adding to the fact that they also have an internal quality assurance program, the quality of VIA results in this study is expected to be much higher than is reported in most studies worldwide , 27.The limitations of this convenience dataset include inclusion only of women with complete data by the study end, the assumption that VIA-negative patients did not have precancer, and the potential limitations of the Onclarity HPV assay , and thAVE shows promise as an assistive technology when performing screen-triage-and treat strategies –15. HoweGiven advanced understanding of cervical cancer etiology and pathogenesis, and effective prevention methods, the critical measure of success/failure is whether we actually save lives and reduce suffering from cervical cancer . CervicaAdditional file 1. Supplemental Table 1: Portability Analysis for J8 images (Comparison of models retained with different-sized Zambia data). Supplemental Figure 1: Assessing AVE predictions under each histologic and HPV genotype result. Supplemental Figure 2: Concentration curve for HIV-positive study population shows what percent of the high-risk study population needs to be referred for management to detect a certain percentage of expected precancers in that study population.


Almost all cases of cervical and anal cancer have been linked to the human papillomavirus (HPV). However, in addition to women who develop HPV-related cervical cancer, both men and women can also develop cancers of the anus, oral cavity, and oropharynx that are attributed to HPV. However, literature on HPV vaccination among boys globally, in Africa, and most especially in Ghana is scarce. Thus, the main objective of this study was to explore the acceptance of HPV vaccination in boys among mothers from selected churches in Accra, Ghana.In this study, a qualitative exploratory design was utilized to enlist 30 mothers who have male children aged between 9 and 12 years from the Greater Accra Region of Ghana. The recruitment of participants was carried out using a purposive sampling technique, and they were subsequently interviewed in-depth in a face-to-face setting, with the entire conversation being recorded for reference. After transcription, the recorded data were analyzed through content analysis.Upon analyzing the data, two (2) primary themes and 11 sub-themes emerged. The research showed that although the majority of the mothers were unaware of HPV in boys, they perceived it as a positive initiative and expressed a willingness to allow their sons to receive the vaccine. However, some participants mentioned certain factors that they believed could hinder the acceptance of HPV vaccination in boys among mothers. These included concerns about injection-related pain, high cost, and fears that the vaccine could make men immoral or infertile.The study revealed poor awareness of HPV vaccination in boys among mothers, and hence, suggested the need to increase the awareness on HPV vaccination in boys among mothers as well as the public to increase its acceptance. HPV has been linked to nearly all cases of cervical and anal cancer and was responsible for 43,371 cases of cancer in 2015 [Sub-Saharan Africa has the highest incidence and mortality rates of cervical cancer, with an annual diagnosis of 34.8 new cases per 100,000 women and 22.5 deaths per 100,000 . In GhanIncorporating boys into a girls-only vaccination program, which has already demonstrated efficacy in United Kingdom, exhibits minimal cost-effectiveness, owing to the high level of protection that males receive through herd immunity. For example, all threshold prices escalate when utilizing a discount rate of 1.5%, and the addition of boys to the program becomes financially feasible, ranging from £36 to £47 . In addiThe primary approach for preventing cervical cancer involves vaccinating both males and females against human papillomavirus (HPV), while secondary prevention concentrates on screening and treating women who are 30 years and older . DevelopHPV infection can lead to cancers of the anus, oral cavity, and oropharynx in men, as well as genital warts, resulting in an equivalent burden for both genders . It is nOver the years, numerous studies have been conducted in various countries across sub-Saharan Africa (SSA) to investigate human papillomavirus (HPV) vaccination in adolescent females , 20. In The Health Belief Model (HBM) is the theoretical framework that best suits our study. Developed in the 1950s, the model is widely used to study the behavior of individuals regarding healthcare and disease prevention , 25. TheThis research is particularly significant because it will help to raise awareness about the importance of HPV vaccination for boys, which has been relatively under-studied in Africa, particularly in Ghana. By increasing awareness of the benefits of HPV vaccination for both males and females, we hope to improve the acceptance rate of the vaccine and encourage more parents to vaccinate their sons against HPV. Furthermore, our findings will be useful in informing policy decisions related to the cost of HPV vaccination, as well as other related healthcare services. By understanding the factors that influence vaccine uptake, targeted policies that address specific barriers to vaccine acceptance, reduce costs, and increase the overall uptake of HPV vaccination could be developed.A qualitative exploratory design was employed to fully understand the participants in terms of their knowledge, acceptance, and attitudes toward HPV vaccination in their sons. A qualitative exploratory design is suitable to examine vaccination views and acceptance due to the novel research area and the potential to explore complex and nuanced aspects of individuals’ beliefs, attitudes, and behaviors related to vaccination. Employing this method is advantageous when investigating under-researched areas such as HPV vaccination in boys, as it enables researchers to gather rich data on the factors that affect vaccine acceptance or rejection among mothers by obtaining an in-depth understanding of participants’ experiences and perspectives..The current study was careful to include mothers who had male children between the ages of 9 to 12 years, with no age limits placed on such mothers.Participants exempted from the study were those, who were neither parents nor in the position of parenting, either through biological means or through adoption. Also, mothers with male children below 9 years and 12 years and above. Lastly, mothers who were unwilling to partake in the study.The study employed the use of purposive sampling techniques to select the participants of the study. It was opined that the rationale for this technique helps improve the trustworthiness of the data and results . This isEstimating a qualitative sample size prior to conducting a study is an intrinsically challenging approach, which is particularly accentuated in more interpretive instances of qualitative research . In the Ethical clearance was obtained from the Dodowa Health Research Centre Institutional Review Board (DHRCIRB/145/11/21). Initially, an introduction and the ethical clearance form were submitted to the chosen district within the Greater Accra Region. The researchers also sought permission from the leaders of the churches located in the district. Upon receiving approval from the leaders of the selected churches, the researchers introduced themselves to the participants, elucidated the study’s objectives, and provided a clear explanation of the keywords used in the research instrument. Subsequently, a semi-structured interview guide prepared by the researchers was utilized. The guide had 3 sections that elicited questions on the socio-demographic characteristics of participants, the knowledge, and barriers to HPV vaccination in boys. The guide was pre-tested among 4 participants from two different churches in Accra which was not included in the main interviews.After conducting a pilot study, face-to-face interviews were carried out in English at the selected churches for the study. The researchers used audio recorders during the interviews to document the participants’ views, paying adequate attention to avoid missing any vital information. The contact information of interested eligible participants was collected, and interviews were scheduled at a time and place that was convenient for them. The interviews were conducted in different settings, including the church outside of session times and the participants’ homes. To minimize disruptions or distractions, only the researchers and participants were present during the interviews. Mothers were selected for the interviews due to their significant influence over their children’s decision-making, particularly for those under 18 years of age. Moreover, the mothers were primarily responsible for their children’s healthcare needs and well-being.At the time of the interview, participants who showed unwillingness were allowed to opt-out of the interview. Those who agreed to participate in the study were assigned pseudonyms in identification to enhance confidentiality. The researcher explained all questions in simple language to participants to answer correctly. The discussions lasted between fifty (50) to sixty (60) minutes. Data collection took place over a period of three months and strict adherence to COVID-19 safety protocols was observed. Social distancing was maintained during the interviews, and both researchers and participants wore face masks. A box containing face masks and hand sanitizer was readily available to ensure compliance with the protocols. Participants were thanked for their valuable contributions at the end of each interview.Data analysis is defined as the process of cleaning, transforming, and modeling data to find useful information for decision-making . InductiThere are six stages in thematic analysis . The sixThe second stage involves assigning codes to the data collected. This was done by labelling participants’ ideas with 2–3 words that had the same meaning as the participants’ words. The third stage involved the generation of themes, Comments, and expressions of close nature that were grouped together to form sub-themes. Finally, was reviewing the themes. The themes were examined and improved by collapsing some themes into other themes. This was to ensure that all the data followed a consistent pattern. For the purposes of this study, the developed codes were tabulated and arranged into main and sub-themes.Methodological rigor is termed as the trustworthiness of a qualitative study . The rigTransferability of a research finding is the degree to which it can be applied in other parts and studies . PurposiThe socio-demographic characteristics examined from the 30 respondents included: age, marital status, number of children, educational status, occupation, and ethnicity. The age of participants ranged from the least age 25 years) to the highest which was 50 years. Half of the participants (50%) fell within the age group of 31 and 40 years, followed by the age range of 41years to 50 years with a percentage of 33.3 and the least age group was between 25years to 30 years having only 16.7% of the participants in that age category. Most of these participants (83%) were married with families, followed by 10% of them being single and 1% of the participants being divorced and widowed respectively. The rest of the data is presented in Table 5 years tTwo primary themes and eleven sub-themes emerged from the data. The first theme focused on the mothers’ knowledge of HPV vaccination, while the second theme explored the barriers to HPV vaccination for boys.The first theme, “Knowledge of mothers on HPV vaccination,“ had 5 sub-themes, which were views on HPV vaccination, mode of transmission, HPV vaccination centers, the effectiveness of HPV vaccination, and misconceptions about HPV vaccination. The subthemes categorized under the second theme (barriers) were cultural barriers, religious barriers, fear of pain from HPV vaccination, cost, side effects, fear of HPV vaccination making men immoral, and fear of HPV vaccination causing infertility in men.Mothers’ knowledge about HPV vaccination varies widely. Some are well-informed and recognize its importance in preventing cervical cancer, while others have misconceptions about the vaccine’s safety and efficacy. The first theme includes five sub-themes that cover mothers’ views and knowledge of HPV vaccination, the mode of transmission, vaccination centers, vaccine effectiveness, and misconceptions surrounding the vaccine. See Fig. “The HPV vaccination in boys is a good thing since I know all vaccines protect against a particular disease. So for me, I want my son to wait since he is too young (9 years) till he is 18 years before I will send him to be vaccinated” N13I don’t really know about this vaccine you are talking about, but if there is a vaccine like that, I think it is a good idea and I do not know why I should not let my sons go for it” N2.“Every day you people bring us something new. The research revealed that mothers held varying opinions on giving their young sons the HPV vaccine. Certain mothers believed that their sons were too young to receive the vaccine, despite its benefits in preventing HPV, while others had no reservations about vaccinating their male children.“This HPV vaccination is new to me, honestly this is my first time hearing of it, and besides my twin boys have already been immunized against TB, Measles, and others, so why should they now take the HPV vaccine again? I think they can all protect him against this virus you are talking about.” N4.Below are responses of participants who mentioned that they were not aware of HPV vaccination and believed that their children have already been vaccinated and hence there is no need for further vaccinationThe HPV is not an African thing is only the whites who get it. I don’t personally know anyone nor have I heard of anyone who has it so why must my child take it?.This sickness is for the white people just like the covid-19. They should leave us alone” N11.“What I know about this HPV is that if you don’t have sex then you are less likely to contract it and also unlikely to transmit it to another person. Per this understanding, I don’t think my son has to take the vaccine since he is not sexually active, and you can only contract it through sex” N7Some held the belief that HPV vaccination was unnecessary as it is sexually transmitted, and their sons were not sexually active.“My boy plays with a lot of children in my vicinity, so does this mean he is at risk of contracting the virus from them? Besides, when the health talk was given at church, I remember the lady saying it affects women so we should be concerned about our girls. What has this got to do with my boy? …” N20.Few participants in this study were unaware of the mode of transmission for HPV“My concern is where to locate such places if indeed vaccine will be made available. You know Ghana, sometimes you go to public hospitals and you don’t get all the services you need. You must move to another place before you can do a certain test requested. It makes it stressful; that’s why if they are going to do this vaccination then it should in at least every district hospital. This way I know that when I go to this facility I’ll get the vaccine and not be roaming” N17“This is a challenge for those of us staying in the rural areas, we only have access to health centers, and these screenings are not done there so it is even a problem where to get it if we agree to vaccinate our boys.” N8“I have heard that some women go for Cervical Cancer screening at the KorleBu Teaching Hospital and also take the vaccine there, but I don’t know if boys can also get the HPV vaccination at the same place” N19The study found that the majority of mothers were unaware of where the vaccination would be administered, and those residing in rural areas believed that accessibility would be a challenge even if the vaccination were introduced.“My concern is not allowing my boys to take the vaccine, but I am worried about the fact that after they take it, they might introduce another vaccine just like Covid 19 as a booster”. N14“I don’t think it will be 100% effective, because, I took a Covid 19 vaccine, and after I was still diagnosed of Covid 19 so I don’t believe any vaccine gives 100% protection.”N9“If the doctors and the nurses are saying this vaccine works then I’ll believe you. After all, it is your field and you know what you’re doing. Just like the immunizations you give our children you know what you are doing and also tell us why you are doing it so I know it’s for the good of my children. So it is the same here too” N22Some believed that their perception of the vaccine’s effectiveness was influenced by the testimonials provided by healthcare providers as follows: Their concerns varied, with some questioning the effectiveness of the vaccine, as they feared a newer, more potent version may be introduced after its initial release. Additionally, they worried that their children may still contract HPV even after receiving the vaccine.:These new vaccines that are been developed currently like the Covid 19 vaccine, I hear have microchips in them that can help in tracking, monitoring and also controlling human beings. So I didn’t take the covid vaccine how much more allowing my son to take this HPV vaccine. I honestly don’t believe that this HPV vaccine will protect my son”.N18““I don’t believe there is any disease like that…you people just want to introduce some disease into our children then later come back and tell us you have a cure. It is just a means for you health workers to extort money from us…as for me, I won’t vaccinate my son, you people say this, tomorrow that I’m tired of you people” N27.Mothers held various misconceptions about the vaccine, including the false belief that it contained a tracking microchip, denial of the existence of cervical cancer, mistrust in the vaccine, and suspicion that it was a means of extorting moneyThis refers to the challenges and obstacles that prevent boys from receiving the HPV vaccine, such as social stigma, lack of awareness, safety concerns, and cost issues. Addressing these barriers is important to improve vaccination rates. The subthemes included cultural and religious factors, fear of pain and side effects, concerns about cost, and fears of perceived negative impacts on morality and fertility. See Fig. “ I am Fante, my tribe and culture do not have any issues with young boys being vaccinated, once it’s for a good course then they have no issues. But come to think of it, in this 21st century, do people still allow their culture to influence their decision when it comes to health(laughs). Well, my culture has no issues with this. Even if it has, life is more important to me. N29“Culture or no culture I am all for this HPV vaccination, I am from a royal family, we rely greatly on herbal medicine. It was in the olden days that orthodox medicine wasn’t trusted but now, because of exposure it has been accepted. So my culture should not prevent me from getting my son vaccinated”N26.The majority of mothers in this study believed that culture had little influence on vaccinating children, as indicated below.“I come from the Northern part of Nigeria, and we don’t joke with our male children, especially the first born, any form of needle, sharp object that will cause pain we are really hesitant about it, so this HPV that I know little about, I won’t expose my son, no harm must come to him” N23.On the other hand, some mothers expressed their concerns and admitted to the fact their culture is a contributory factor to their vaccine hesitancy.if my son follows Christ and is obedient, then there is no need for him to take the vaccine because the disease is sexually transmitted. As a Christian, you have no business fornicating, so he doesn’t need the vaccine. I would rather nurture him the fear of the Lord to prevent this HPV virus” N1.“Ideally “I have read in the Bible where a lot of good standing Christians received their healings, so I believe God will protect my children from all kinds of diseases if I trust in him” N5Most mothers also expressed their belief that they need not worry about vaccines since they have faith in God and believe that they and their children are fully protected.“I am a little worried about the pain my son will experience after taking the vaccine. This vaccine is new to me and I don’t how he will feel after the vaccine. Even with the TB vaccine and others, my son was in pain for quite some time, it wasn’t easy for me at all”. N2“They are kids, I hope it won’t be too painful, even with me when I took the Covid-19 vaccine I could barely lift my arm for like 3 days, when my boy start crying, you can’t control him. N20One of the major concerns expressed by mothers in this study was the fear of their children experiencing pain following vaccination, which made them hesitant to allow their children to receive the vaccine.“Well, I am not too bothered about my son experiencing pain, because it is expected. I just have to deal with the pain after he takes the vaccine. Injections always come with pain and you know it.” N25Few of the participants were unconcerned about the pains that will be experienced by their boys resulting from the HPV vaccine.“I hope the HPV vaccine will be for free because most of the vaccines that our children receive when they are born are for free. The government can also include it in the National Health Insurance Scheme, especially for those in the villages.” N21“Honestly this vaccine is not compulsory, but it is in the best interest of our sons, if you the health workers start the vaccination exercise and it is expensive, I won’t bother myself. So please make sure that the vaccine is affordable if not forget it (laughs)” N16The cost of the HPV vaccine was also a major concern expressed by the mothers, who suggested that the vaccine should be made available at a lower or no cost for them to allow their children to receive it.“My son’s wellbeing is my top most priority, so I am not looking at the cost. If the HPV vaccine will protect him why not, I am willing to pay any amount. God forbid but he dies right now because of this HPV, I can’t resurrect him. So prevention is better than cure” N11Few were unconcerned about the cost of the HPV vaccine.“Allowing my son to take HPV vaccination is like telling him that he is free to sleep around because he is protected. Children in this 21st Century are always looking for opportunities to justify the wrong things they do. Can you imagine the kind of things they would get themselves into knowing that they have been vaccinated against a sexual infection?” N24“I know the purpose of this vaccine is to protect our young boys, but indirectly it is going to promote sexual promiscuity, what worries me the most is that they are young and very curious at this stage, I am just wondering the kind of things they will be doing after taking a vaccine like this.” N11Some participants in the study believed that administering the HPV vaccine to their young boys could create a false sense of security and lead them to engage in sexual activities without the fear of contracting the virus. They were concerned that this could potentially lead to negative consequences.I stand to be corrected but I think this vaccine can affect my sons’ ability to have kids, this vaccine was created for sexual infection. People react to medications in different ways what if my son’s reaction leads to infertility, what will I do? N19I don’t want to get myself into this HPV vaccination and regret it later. If you can show people who have taken the vaccine and have kids, then I will be fully convinced N4On other the hand, some mothers were convinced that the HPV vaccine would not cause serious side effects to their boys.“I don’t think my son will become infertile from taking the vaccine, I believe the vaccine would been tested several times before being given to humans, so I doubt it would cause infertility.” N22Fear of potential side effects is one of the main reasons for vaccine hesitancy. Infertility in their young boys stood out as their greatest fear with regard to the side effects especially because it was new to them.The study revealed insufficient knowledge of HPV vaccination among mothers, however, they perceive the vaccine to be of immense benefit on the basis that vaccines help protect children from disease. Due to this, the mothers recommended the need for healthcare professionals to increase information on HPV vaccination to help increase the acceptance rate. This implies that mothers will be more willing to send their male children for vaccination if they are told more about the vaccine and its benefits. Similarly, a study revealed that most fathers and mothers showed poor knowledge of the vaccination which can be attributed to their decision to allow their young boys and girls to take the vaccine . The HBMThe present study revealed that most participants exhibited a sound understanding of the mode of transmission of the HPV virus, recognizing it as a sexually transmitted infection. This understanding led some participants to perceive HPV as more prevalent among females than males. However, some participants believed that safeguarding their sons from premarital sex could provide protection against the virus, given its sexual transmission. These attitudes underscore the need to enhance public awareness about HPV, particularly among those who believe it to be a disease that primarily affects women. Similarly, a study found that a mere quarter of participants 34.3% were aware that HPV is a sexually transmitted infection, and only 40.4% were aware of its association with cervical cancer . These fIn the current study, participants raised concerns regarding the availability of HPV vaccination centers in Ghana. Specifically, they noted that cervical cancer screening and vaccination centers were not widely available in hospitals across the country, leading them to believe that the situation would be similar for HPV vaccination in boys. Participants emphasized that their willingness to vaccinate their sons would depend on the availability and accessibility of the vaccine and associated vaccination centers. In light of these concerns, participants recommended that the vaccine be made widely available in clinics across the country to ensure ease of access. Interestingly, a study conducted by Rezqalla et al. in Kuwait found that a significant majority of female school teachers (88%) were unaware of the availability of the HPV vaccine . This hiThe results of the present study shed light on the perceptions of mothers regarding the effectiveness of the HPV vaccine. The doubts expressed by these mothers were largely influenced by their previous experiences with the COVID-19 vaccine, which caused them to question the ability of any vaccine to offer 100% protection. As such, it is crucial for healthcare workers to provide comprehensive education on vaccines, including their mechanisms of action and potential benefits, to alleviate the concerns of these mothers. This, in turn, could foster greater trust in the HPV vaccine and increase the likelihood of their willingness to vaccinate their sons. Notably, a majority of the parents in this study voiced concerns about the safety and efficacy of the HPV vaccine .Most of the participants in the study had an accurate understanding of the HPV vaccination and welcomed its implementation for boys as a positive development. They recognized that this would not only benefit their sons but also contribute to the prevention of cervical cancer in their daughters. As a result, the more informed the participants were about the vaccine, the more likely mothers were to support the idea of vaccinating their young boys against HPV. It is noteworthy that a significant proportion of participants in another study held misconceptions about vaccines in general, with around 85% underestimating the magnitude and scope of clinical trials conducted for vaccines . The finThe study found that most of the participants who were interviewed did not encounter cultural obstacles when it came to vaccinating their young sons. Some participants believed that cultural beliefs should not impede individuals from making informed decisions about their health, particularly in the modern era. These mothers should be encouraged to discuss the advantages of the HPV vaccine with other mothers and encourage them to consider having their sons vaccinated. Notably, Ng and Tan’s research revealed a negative correlation between cultural rigidity and the inclination to receive vaccines .This finThe study’s findings showed that most of the participants did not encounter any conflict between their religious beliefs and vaccinating their sons against HPV. They held the belief that it was God who granted health professionals the knowledge and skills to develop vaccines, and thus had no reservations about having their sons vaccinated. These mothers could collaborate with spiritual leaders to promote the benefits of HPV vaccination to other mothers. Other researchers has demonstrated that religious convictions can have an impact on health-related decisions . .The study’s findings showed that, among the potential side effects identified, the possibility of infertility in their sons was the most significant concern for some mothers. They feared that the HPV vaccine could have a detrimental impact on their sons’ reproductive systems, particularly since the vaccine protects against a sexually transmitted infection. Other participants requested evidence to reassure them that the vaccine did not impair male fertility before trusting the HPV vaccine. To allay these fears, it is crucial to provide such mothers with evidence of the safety of the HPV vaccine. It is noteworthy that a survey demonstrated no evidence of increased infertility in women who received the HPV vaccine .Some mothers expressed concern over the potential for pain associated with the HPV vaccination. Their apprehension stemmed from prior experiences with childhood vaccinations or the Covid-19 vaccine. They found it stressful and upsetting to see their children in pain and were hesitant to have them receive the HPV vaccine. It is crucial to provide these mothers with information on strategies they can use to help their children manage any discomfort and to reassure them that the pain is short-lived. Baxter et al. identified fear of needles as a barrier to the uptake of the HPV vaccine, while other barriers to cervical cancer screening and vaccination in Ghana included the high cost and doubts about its effectiveness , 44.For practice, the study highlights the importance of targeted public health education campaigns to increase knowledge and awareness about the HPV vaccine and its benefits. It is important for healthcare providers to be able to effectively communicate with parents about the importance of HPV vaccination and address any misconceptions or concerns they may have. The study also underscores the importance of making the HPV vaccine accessible and affordable for all families. For future researchers, this study provides important insights into the specific barriers to HPV vaccination in boys and the factors that influence mothers’ decision-making. The study highlights the need for further research to identify effective interventions to address these barriers and improve HPV vaccination rates in boys. Policymakers should also consider ways to address the specific barriers to HPV vaccination in boys, such as concerns about pain or fertility, in order to increase vaccination rates and reduce the burden of HPV-related diseases.In conclusion, the study highlights a lack of awareness among mothers regarding the HPV vaccine for boys. To increase its acceptance, there is a need to increase awareness of the vaccine not only among mothers but also among the public. Such efforts could help to dispel misconceptions, address concerns, and increase the uptake of the vaccine among boys.