Exposure to different types of vaccine information in social media can resultin parents making disparate vaccine decisions, including not followingnational guidelines for human papillomavirus (HPV) vaccination. We sought tocharacterize parents’ exposure to and engagement with information about HPVvaccination in social media, and the associations between exposure to suchinformation and vaccine decisions for their adolescent children.In 2019, we conducted a web-based survey with a national sample of 1073parents of adolescents who use social media. The survey assessed whetherparents have seen information in favor, against, or mixed about HPVvaccination. Multivariable logistic regressions assessed correlates ofvaccine decisions, including HPV vaccine initiation, delay, and refusal.Sixty-one percent of parents reported that their children have initiated HPVvaccination. Over one-third of parents (37%) reported seeing HPV vaccineinformation on social media, which was either in favor (20%), against (5%),or a mix (12%). Parents exposed to information in favor were more likelythan those who saw no information to have initiated HPV vaccination . Parents exposed to information against vaccinationwere more likely to have delayed  or refused HPV vaccination. Exposure to mixedinformation was also significantly associated with vaccine delay andrefusal.Our findings suggest that the type of information seen on social mediaregarding HPV vaccination may influence the decisions parents make aboutvaccinating their children. Efforts should be sought to increase onlineinformation in favor of HPV vaccination and combat vaccine misinformation insocial media. For instance, parents withincreased social media use are more aware of the human papillomavirus (HPV) vaccinethan parents with lower or no social media use.6Social media is a common source of health information for many U.S.parents,7 and information against HPVvaccination is both prevalent and growing.8 A recent study examined storiesabout adverse vaccination events posted on Facebook, mostly unverified, and foundthat the HPV vaccine was the most frequently mentioned type of vaccine in thiscontext.9 Another study, summarizing 10 years of HPV vaccine-relatedFacebook posts, found that 45% of posts from 2006 through 2016 had messaging againstvaccination  and focused on barriersmore than benefits.8 Analyses on other social media platforms like YouTube, Twitter,and Instagram have also shown majority of the vaccine-related content to be againstthe HPV vaccine10 or a mix of information in favor and against.12 Equallyconcerning is the high level of engagement with the anti-vaccine content on socialmedia, with information against HPV vaccination gaining more “likes” than posts infavor of HPV vaccination.13The HPV vaccine is heavily discussed on social media,14 A growingnumber of studies have explored the potential role of HPV vaccine information onsocial media and parents’ vaccine attitudes and behaviors toward vaccinating theirchildren.15 Dunn and colleagues found that prior exposure to tweets againstHPV vaccination was associated with expressing negative opinions regarding thevaccine.16 Another study reported that parents who had seen informationagainst HPV vaccination on social media were more likely to believe the vaccine tobe unsafe and harmful to their child.17 Healthcare providers havealso listed social media content against HPV vaccination as a major barrier toimprove HPV vaccination rates among their adolescent patients.18 In this sameline, Margolis et al. reported that U.S. parents who had heard stories of harm dueto HPV vaccination were less likely to initiate the vaccine series and more likelyto delay or refuse the vaccine compared to parents who heard no HPV vaccinestories.19 Interestingly, exposure to stories about diseases the HPVvaccine could have prevented (in favor of vaccination) was not associated withinitiation, delay, or refusal.19 This prior study onlyassessed exposure to stories about harms and preventable diseases and focused onmultiple communication channels .19The 2020 National Immunization Survey (NIS)-Teen reports that only 61% of adolescents13-17 years old were up-to-date with their HPV vaccination.Given the growing literature indicating that exposure to vaccine information postedon social media influences HPV vaccine attitudes and behaviors, it is important tounderstand the role of different types of vaccine information on parents’ decisionsabout HPV vaccination. Other studies that have evaluated such associations have usednarrow definitions of information exposure , focused on exposure froma single social media platform, or not assessed engagement with information afterexposure. Therefore, we sought to better understand exposure to broad types ofvaccine information in social media using data from a U.S. sample of parents ofadolescents. The aims of our study were to (1) characterize the type of informationparents had seen about the HPV vaccine on social media, (2) describe how parentsengage with such information, and (3) evaluate the associations between exposure tovaccine information on social media and vaccine decisions for their adolescentchildren.20Invitations to our online survey were emailed to a random sample of 11 000 panelmembers, and 6470 responded by visiting the survey and completing theeligibility screener. Eligible participants were parents of at least one 11- to17-year-old child living primarily in their household. We focused on U.S.parents because national guidelines approved by the Centers for Disease Controland Prevention’s (CDC) Advisory Committee on Immunization Practices (ACIP)recommend HPV vaccination for minors ages 11-17.21 A total of 1109 parentswere eligible, provided implied consent (participants consented to answer a10-minute online survey), and completed the survey between July and August 2019.After accounting for ineligible panel members (n = 5270) and excludingrespondents who failed to complete at least two-thirds of the survey (n = 91),the survey response rate was 58%.22 The survey was programmedto stop recruiting when it reached 1200 participants, regardless of surveycompleteness. Participants with more than 1 eligible child were instructed torespond about the child with the most recent birthday. For this analysis, 36participants who reported not using social media at the time of the survey wereexcluded, producing an analytic sample of 1073 parents. The Penn State Collegeof Medicine’s Institutional Review Board approved the study protocol onSeptember 13, 2018 (Study #00010362).Participants were members of an existing market research panel of U.S. adultsmaintained by Qualtrics, a commercial software and survey research company. Thepanel employs a range of recruitment methodologies to produce a sampling framethat is not overly reliant on any distinct demographic group.19The questionnaire assessed 3 HPV vaccine decisions , first orienting parents to HPV vaccination with the statement,“The next questions are about the human papillomavirus (HPV) vaccine. It’salso called Gardasil.” Our primary outcome, HPV vaccine initiation, wasassessed with the question, “How many shots of the vaccine has [child’sname] had?” Response options were dichotomized into initiated HPVvaccination  and not initiated (“none” and “I don’t know”).Our secondary outcomes were HPV vaccine delay and refusal. Parents wereasked if they have ever delayed getting the HPV vaccine for their child withthe following question (yes/no), “Has there ever been a time when youdelayed or put off getting the HPV vaccine for [name]?” HPV vaccine refusalwas assessed with the question (yes/no): “Has there ever been a time whenyou refused or decided not to get the HPV vaccine for [name]?” Vaccine delayand refusal questions were adapted from the literature and were only askedto parents who reported having discussed HPV vaccination with a healthcareprovider (n = 878).The questionnaire assessed whether participants were exposed to informationabout the HPV vaccine on social media with 1 question (yes/no), “Have youseen information  about the HPVvaccine on social media even when you were not looking for it?” Parents whoreported seeing information were then asked to categorize it, with responseoptions: completely in favor, mostly in favor, mostly against, completelyagainst, or a mix of both. Based on these 2 items, we created afour-category variable of exposure that captured whether parents had seeninformation: in favor of HPV vaccine, against HPV vaccine, a mix (in favorand against), or neither .The questionnaire queried parents’ additional questions based on the reportedstance of information seen. These questions were grouped in 2 blocks, infavor or against. Those who saw a mix of information (n = 126) were randomlyassigned to 1 of the blocks and responded to questions either about theinformation they saw in favor (n = 58) or against (n = 68) HPV vaccine. Wechose this process of random assignment for parents who reported seeingmixed information in order to minimize their burden taking our survey aseach block of questions added eleven items. Each block of questions askedparents to further characterize the information seen, with responsesincluding parents’ stories, news reports, information from health or medicalorganizations, information from advocacy groups, stories from cancerpatients or survivors, celebrities’ opinions, pharmaceutical companyadvertisement, or something else. Parents who selected more than 1 type wereprompted to choose the single information type they recalled most. Parentsalso indicated their engagement with the information seen on social mediawith the following options: read it, liked it , posted content, reposted content, commented on apost, blogged or participated in an online forum, or ignored it.Sociodemographic variables of the sample included parents’ sex, age group,race/ethnicity, and educational attainment. Household characteristics wereannual income and state of residence (categorized in 4 U.S. regions). Thesurvey also assessed the sex and age of the index child.23Content and face validity were established for the survey instrument byhaving it reviewed by 4 researchers experienced in survey research andvaccine communication studies. More details about our measures and surveydevelopment are available elsewhere.24 We reported multivariableanalyses with odds ratios (OR) and their corresponding 95% confidence intervals(95% CI). We modelled type of information exposure as a categorical variable . We conductedseparate regression analyses for each HPV vaccination decision . The first model (initiation) compared parentswho had versus had not initiated the HPV vaccine series for their children usingthe full sample. The other 2 models  compared parents whoreported delaying or refusing HPV vaccination versus those that had not within asubset of parents who reported discussing HPV vaccination with their child’sprovider. Analyses were conducted using STATA/BE25 and all statistical testswere performed at the .05 significance level.Sociodemographic variables were reported for the full analytic sample (n = 1073)using frequencies . DiffereParents were split between reporting on a daughter (51%) or a son (49%) , and theOverall, 20% of parents reported seeing information in favor of HPV vaccination,5% against HPV vaccination, and 12% saw a mix of information in favor andagainst HPV vaccination. Among parents who reported seeing favorable information(n = 275), the most recalled content was from health or medical organizations(30%), followed by parents’ stories (20%), pharmaceutical or industryadvertisement (16%), and news reports (16%) . On the Parents who had seen information in favor of HPV vaccination reported varyinglevels of engagement with the content, including reading (76%), liking (23%),posting (10%), and commenting (9%) . ParentsSixty-one percent (n = 659) of children had initiated HPV vaccination at the timeof this survey. Out of 217 parents that indicated seeing only information infavor of HPV vaccine on social media, over two-thirds  reportedthat they had initiated HPV vaccination. In a multivariable analysis, parentswho only saw information in favor of HPV vaccination were more likely  to have initiated HPV vaccination than those who hadseen no information . ExposurAmong 878 parents who reported having discussed HPV vaccination with theirchild’s provider, almost one-fourth  said that they have delayedtheir child getting the vaccine, and 17% (n = 153) reported refusing HPVvaccination for their child. Parents who had seen information against HPVvaccination only were more likely to have delayed  of parents in our study had seenfavorable vaccine information, which is almost twice as many who reported seeinginformation against vaccination (17%), whether alone or mixed. Our finding alignswith recent studies showing that social media content supporting HPV vaccination ismore prevalent and reaches more users than negative messaging. For example, Masseyet al. reported that 39% of tweets about HPV vaccination express positive sentimentversus 25% of tweets that showed negative sentiment, and that a larger number ofTwitter users were exposed to positive sentiment than to negativesentiment.28 However, despite having a more limited level of exposure,anti-vaccine information posted on social media is especially powerful ininfluencing parents to decide against on-time HPV vaccination for their children, asshown by our results and those of other studies.19 This aligns with researchshowing that negative information is more influential in shaping perceptions anddecisions than positive information.29 Public health messagingdemonstrating the benefits of HPV vaccination might consider first showing thepotential health risks  when one doesnot vaccinate. Also, public health campaigns promoting HPV vaccination on socialmedia should be more frequent so that the negative content is less likely to be seenand, as such, becomes slightly less influential.Overall, 37% of parents in our sample reported seeing information about the HPVvaccine on social media, similar to a prior report showing 41% of informationexposure among U.S. parents of adolescents who had not yet completed the HPVvaccines series.13 Parents’ stories were the second most recalled information infavor of vaccination (20%), but more than half (51%) of parents who reported seeinginformation against vaccination recalled these stories from other parents the most.Kearny et al. similarly reported that personal stories about HPV vaccine onInstagram were significantly more anti-vaccine (55%) than pro-vaccine(45%).13 Because of the potential persuasiveness of these personalstories, many healthcare organizations and vaccine advocates are now promoting theuse of stories from parents and cancer survivors to reach and educate the generalpublic about the importance of HPV vaccination, especially for individuals with lowliteracy.27 Moreover, a recent study with U.S. parents of children ages9-14 indicated that parents want to learn about the HPV vaccine through other parentexperiences, especially when the information aligns with science supporting thevaccine.32 We found that news reports seen on social media were a commonsource of information against vaccination. Keim-Malpass et al. reported that newsand lay media were a common source of tweets regarding HPV vaccination with almostone-fourth (24%) showing negative sentiment and the rest being positive orneutral.12 As such, training for journalists or health-relatedcommunicators may be needed to help counter misleading information about vaccinationthat appears from news outlets on social media.This study also found interesting results about the characteristics of informationseen by parents. Among parents who reported seeing information in favor of HPVvaccine, almost one-third (30%) said that the most recalled content was from healthor medical organizations. Recent content analyses of social media show thathealth-related users or advocates  create significantly more positive HPV vaccine content than otherusers.13 Another study reported that positive-sentiment tweets aboutHPV vaccination generate a significantly higher number of retweets per tweet thannegative tweets.28 Studies have also shown that engagement with social mediacontent varies depending on features like showing images, hashtags, tags, or links,as those features may provide higher visual appeal and contentcredibility.30 Our study did not ask participants about the prevalence ofthese features on the social media content they saw but the literature shows thatthese are common.28 We also know from prior research that the type of informationis important for engagement. For example, Kearny et al. reported that personalstories receive nearly twice as many likes as informational posts about HPVvaccination in Instagram.13 Furthermore, attempts to reach parents using personalstories on Facebook have generated high engagement and positive dialogue around theHPV vaccine,31 suggesting that social media could be a promising space todisseminate HPV vaccine information if it is done in a credible way.32 Futurestudies should evaluate what strategies can be used to increase the credibility oftrusted sources of vaccine information  and the role that literacy plays in a person trusting in one socialmedia source more than another.A majority of parents who saw information, either in favor or against vaccination,reported engaging with that content, mostly reading it, but also by liking,commenting, or reposting it. Other studies have reported mixed findings in terms ofengagement. For example, pro-vaccine posts were liked significantly less frequentlythan anti-vaccine posts in a study evaluating HPV vaccine content onInstagram.23 The most supported standardby parents was to fact-check the information before it is posted online (51%), whichallows social media platforms to flag it as inappropriate beforehand.23 Moreso, thestudy found that parents who had been exposed to information in favor of the HPVvaccine were more likely to support social media standards to combat vaccinemisinformation, again showing the potential positive impact of favorable vaccineinformation on social media as in this study.23 Other studies also reportthat social media messaging about HPV vaccination, including personal stories, fromhealthcare professionals can help engage parents in vaccine conversations andmotivate them to vaccinate their children.32 With our finding that themost recalled content by parents who had seen favorable HPV vaccine information camefrom health or medical organizations (30%), it is important to seek approaches tomotivate healthcare professionals to continue disseminating science-basedinformation about vaccines on social media. Equally important, when communicatingwith parents during child wellness visits, providers should use presumptiveannouncements to clearly recommend HPV vaccination and address parents’ concernswith evidence-based messages.33 Providers can use thisopportunity to understand whether parents’ vaccine concerns stem from misinformationthey have seen on social media and then, provide answers appropriate to parents’literacy level or direct them to trusted resources where they can access accuratevaccine information.A previous study by our team found that many parents also support measures that wouldaid in social media becoming a space with accurate vaccine information. We foundthat 61% of U.S. parents of adolescents were in favor of implementing at least 1social media standard to reduce vaccine misinformation.34Study strengths include using a large, national sample of parents and an adequateresponse rate. Importantly, the proportion of minority participants in the studyapproximates the national distribution of non-Hispanic black and Hispanic adultgroups. This study had several limitations. Our questionnaire only asked parentsabout information specific to the HPV vaccine that they have seen on socialmedia. It is possible that parents saw information either in favor or againstvaccines from other modes of information delivery that may have contributed totheir attitudes and decisions regarding HPV vaccination. Temporality of eventswas not assessed and, therefore, it is unknown if the information parentsreported exposure to on social media was seen before or after their child’svaccination decision or maybe on a more continuous basis. Moreover, our studydid not assess the level of engagement with each social media platform thatrespondents reported using, limiting our ability to understand varying exposureto HPV vaccine information across platforms. Lastly, this study relied onself-reported data for our vaccine decision variables without verifyingparticipant responses using immunization records, but studies show that parents’recall of this information is fairly accurate.Our study suggests that the type of information seen on social media regarding HPVvaccination may play a role in the decisions parents make about vaccinating theirchildren. Efforts should be sought to increase online information in favor of HPVvaccination and combat vaccine misinformation on social media. Future approachesshould seek to strengthen the inclusion of healthcare professionals in interventionsto provide factual vaccine information considering that healthcare organizationsrepresented the most recalled content of parents who had seen information in favorof the HPV vaccine.CI-Confidence Interval, HPV-Human Papillomavirus, NIS-National ImmunizationSurvey, OR-Odds Ratio, SD-Standard Deviation, CDC-Centers for Disease Controland Prevention, ACIP-Advisory Committee on Immunization Practices.


Progress has been made in the reduction of morbidity and mortality of cervical cancer by the implementation of human papillomavirus (HPV) vaccination programs. This study aimed to assess the awareness of Palestinian women about HPV as well as their knowledge and acceptability of the HPV vaccine and to examine the factors associated with good awareness.This was a national cross-sectional study. Adult women were recruited from hospitals, primary healthcare centers, and public spaces in 11 Palestinian governorates using convenience sampling. A structured questionnaire was used for data collection. For each correctly answered question, one point was given. The total score was calculated and categorized into poor (0–10) and good awareness (11–21).The questionnaire was completed by 7223 women out of 8086 who were approached (response rate = 89.3%). A total of 7058 questionnaires were included in the final analysis; 4403 from the West Bank and Jerusalem (WBJ) and 2655 from the Gaza Strip. Women recruited from the Gaza Strip were younger, getting lower monthly incomes, and with fewer chronic diseases than women recruited from the WBJ.Only 33 women (0.5%) displayed good awareness of HPV and its vaccine with 0.7% of women from WBJ and only 0.2% of women from the Gaza Strip. Completing post-secondary education, being employed or a student, and having a higher monthly income were associated with an increase in the likelihood of having good awareness.Among women who had heard of HPV , only 46 women (8.1%) reported familiarity with its vaccine. Women from the WBJ were more likely than women from the Gaza Strip to have heard about the HPV vaccine (0.9% vs. 0.2%). Most women agreed to receive the HPV vaccine themselves or for their daughters if it was given without cost or with a co-payment. No differences were found in the likelihood of agreeing to receive the HPV vaccine among women in the WBJ versus the Gaza Strip.The overall awareness of HPV and its vaccine was extremely low. Inclusion of the HPV vaccine in the national immunization program could change this, especially as the HPV vaccine appeared to be acceptable. Cervical Cancer (CC) is a major health problem among women with more than 300,000 deaths reported globally in 2020 . The burHuman papillomavirus (HPV) infection has been identified as the most significant risk factor –8. A preVaccination against HPV is one of the primary prevention measures for CC . PreviouThe HPV vaccine is not part of the national vaccination program in Palestine . UnderstThis national study aimed to: (1) assess Palestinian women’s awareness of HPV and its vaccine, (2) examine if there is a difference in awareness between women from the Gaza Strip versus the West Bank and Jerusalem (WBJ), and (3) identify the factors associated with good awareness.A cross-sectional study was conducted from July 2019 to March 2020 in the two main areas in Palestine: the Gaza Strip and the WBJ. About half of the female population in Palestine is of reproductive age (15–49 years) . TherefoEligible women were recruited from hospitals, primary healthcare centers, and public spaces in 11 Palestinian governorates using convenience sampling. The data collection sites were located across Palestine and covered widespread geographical areas to create a study cohort that resembled the Palestinian community –20.A structured questionnaire was designed using questions from previous similar studies –32. A baThe questionnaire consisted of three sections. The first section described sociodemographic data including age, menarche, highest level of education, occupation, monthly income, marital status, knowing someone with cancer, place of residency, and having a chronic disease. The second section evaluated the awareness of HPV. The third section assessed the awareness and acceptability of the HPV vaccine.Yes/no questions were used to assess the awareness of HPV including its transmission and relation to developing any type of cancer. The participant’s knowledge of the availability of the HPV vaccine in the national vaccination program as well as their thoughts if the HPV vaccine could help in protecting against CC was assessed using yes/no/do not know questions. The open-ended recall questions were posed to specify the relationship of HPV with any cancer types, the age at which the HPV vaccine should be first given, and the number of HPV vaccine doses needed. The participants’ responses were then converted to correct/incorrect responses based on the Centers for Disease Control and Prevention information , 34. A 5Eligible women were invited to complete the questionnaire in a face-to-face interview. Data collection was done utilizing the ‘Kobo Toolbox’, a secure, user-friendly tool that can be accessed by smartphones . A speciDescriptive statistics were used to summarize participants’ characteristics. Continuous, non-normally distributed variables were summarized using the median [interquartile range (IQR)] with baseline comparisons performed using Kruskal–Wallis tests. Categorical variables were summarized using frequencies (n) and percentages (%) with baseline comparisons performed using Fisher’s exact test. Since 1450 NIS (about $450) was the minimum wage of Palestinian employees , it was To evaluate women’s awareness of HPV and its vaccine, a scoring system was adapted from previous studies , 37–40. Missing data occurred completely at random. Therefore, a complete case analysis was utilized to handle missing data. Data were analyzed using Stata software version 16.0 .The questionnaire was completed by 7223 women out of 8086 who were approached (response rate = 89.3%). In total, 7058 questionnaires were included in the analysis ; 4403 from the WBJ and 2655 from the Gaza Strip.The median age [IQR] for all women included in the study was 32.0 years  Table . Women rOnly 33 women (0.5%) displayed good awareness of HPV and its vaccine, defined as having a score of 11–21  had heard about HPV; 339 of 4403 in the WBJ (7.7%) and 232 of 2655 women in the Gaza Strip (8.7%). When those 571 women were asked about the mode of transmission of HPV, 95 (16.6%) and 53 (9.3%) answered correctly with ‘sexually’ and ‘mother to newborn’, respectively  correctly answered that HPV can infect both males and females. About one-third  had heard about a relationship between HPV and any type of cancer. Of those, 107 (50.0%) identified CC, 3 (1.4%) identified skin cancer and 2 (0.9%) identified penile cancer. Women from the Gaza Strip were more likely than women from the WBJ to give incorrect answers about HPV-related cancers.Among women who had heard of HPV (n = 571), only 46 (8.1%) had also heard of the HPV vaccine: 40 in the WBJ (87.0%) and 6 in the Gaza Strip (13.0%). Women from the WBJ were more likely than women from the Gaza Strip to have heard about the HPV vaccine (0.9% vs. 0.2%).Women who had heard of the HPV vaccine (n = 46) were asked some questions about it. No differences in the likelihood to give correct answers to these questions were found between women in the WBJ versus the Gaza Strip. When asked about the age at which the HPV vaccine is first given, 19 women (41.3%) answered correctly with a range from 9 to 14 years old Table . In addiNo differences were found in the likelihood of agreeing to receive the HPV vaccine among women, who had heard about the vaccine, in the WBJ versus the Gaza Strip Table . Forty-oThe overall awareness of HPV and its vaccine in this study was extremely low with only 0.5% of the participants having good awareness. Participants from the WBJ demonstrated better awareness than participants from the Gaza Strip. Completing post-secondary education, being employed or a student, and having a higher monthly income were associated with an increase in the likelihood of having good awareness. Conversely, visiting governmental hospitals or primary healthcare centers was associated with a lower likelihood to display good awareness. A small proportion of women who had heard of HPV reported their familiarity with its vaccine. However, women from the WBJ were more likely than women from the Gaza Strip to have heard of the HPV vaccine. The majority of women in this study would agree to receive the HPV vaccine if it was given without cost as well as if they had to pay for it. In addition, most women would agree to their daughters receiving the HPV vaccine for free or at a cost to themselves.Availability and uptake of the HPV vaccine could play a crucial role in the prevention and reduction of morbidity and mortality of CC , 42. ThiEffective implementation of HPV vaccination programs is considered one of the cornerstones to reducing the burden of CC, particularly in low- and middle-income countries , 41–43. A contributing factor to the low awareness of HPV in this study could be the neglect of speaking of HPV, particularly by healthcare workers who are considered a good source of shaping women's knowledge during their visits to healthcare facilities –20. MoreIn line with other studies , 45–47, In this study, being employed and having a higher monthly income were associated with an increase in the likelihood to display good awareness, which is in concordance with a previous study among Lebanese women . EmployeContrary to other studies that addressed CC awareness of symptoms and risk factors in Palestine, women recruited from healthcare centers were less likely to display good awareness of HPV and its vaccine , 19. ThiSeveral factors might contribute to the finding that participants from the WBJ were more likely than participants from the Gaza Strip to have a good awareness level. Firstly, women in the Gaza Strip are limited in their ability to travel, even to get treatment, compared with women in the WBJ. Since 2006, Palestinians in the Gaza Strip have suffered from increased movement restrictions, making it very difficult to leave or enter the Gaza Strip , 59. TheLow knowledge about HPV infection and the vaccine could be a contributor to the poor acceptability of the HPV vaccine , 67. In The findings of this study showed the substantial need to raise women’s awareness of HPV and its vaccine in Palestine. Enhancing school and university curricula with more in-depth information about health-related topics, including HPV infection and vaccine, should be considered. In addition, targeted educational interventions are needed to promote the knowledge of women of the reproductive age visiting governmental hospitals and primary healthcare centers. Moreover, educating healthcare professionals about the impact of HPV on CC and the effectiveness of its vaccine might be vital to achieving a successful launch of the HPV vaccine campaign in Palestine. There is a need to include the HPV vaccine in the Palestinian national vaccination program supported by the good acceptability among women demonstrated in this study .The main strengths of this study include the large sample size and the inclusion of women from different places and governorates across Palestine to resemble the Palestinian community. In addition, the high response rate and the greater proportion of women included in their reproductive age showed a trend toward acceptance of such questionnaires by the target population. Furthermore, the low baseline knowledge about HPV and its vaccine in this study identifies an area for improvement to increase the chances of successful future inclusion of the HPV vaccine in the national vaccination program in Palestine.Limitations of this study include convenience sampling, as it does not guarantee the generalizability of the findings. However, the large sample size, high response rate, and coverage of most geographical areas across Palestine may have mitigated this limitation. Another limitation could be that adolescents were not included, which could have provided an opportunity to explore their awareness and attitudes towards HPV and its vaccine. Nonetheless, assessing adolescents’ awareness may need a different study design . Finally, the exclusion of participants with medical backgrounds might possibly have reduced the number of participants with good awareness. Nevertheless, their exclusion was intended to increase the relevancy of this study to measure public awareness.The overall awareness of women about HPV and its vaccine was extremely low with only 0.5% demonstrating good awareness. Factors associated with good awareness included living in the WBJ, completing post-secondary education, being employed or a student, and having a higher monthly income. Only 8.9% of women who had heard of HPV knew about its vaccine. A low awareness level of HPV and its vaccine could be expected considering the lack of the HPV vaccination in the national immunization program coupled with the absence of public education interventions. Most women showed good acceptance of the HPV vaccine, despite the vaccine not being part of the national vaccination program, which supports the necessary inclusion of the HPV vaccine in the national immunization schedule.


Despite the high risks associated with human papillomavirus (HPV), the HPV vaccination rate of men is far lower than women. Most previous review studies have focused on female vaccination and related affecting factors. However, previous studies have reported that the factors affecting HPV vaccination differ by gender.The aim of this review was to identify the factors affecting HPV vaccine initiation in men through a systematic review approach.A literature review was conducted across 3 central electronic databases for relevant articles. A total of 30 articles published between 2013 and 2019 met the inclusion criteria and were reviewed in this study.In total, 50 factors affecting HPV vaccination in men were identified, including 13 sociodemographic factors and social structure factors, 12 belief-related variables, 4 family factors, 4 community factors, 14 variables related to needs, and 3 environmental factors.To increase HPV vaccination rates in men, strategies targeting young males and their families should consider frequent visits to or contact with health care providers so that health care professionals can provide recommendations for HPV vaccination. Human papillomavirus (HPV) infection is one of the most common sexually transmitted infections (STIs) in all genders ,2. The aA crucial strategy for protecting people against HPV is the prophylactic HPV vaccination, which can prevent initial HPV infection -8. PopulTo increase the uptake of HPV vaccination among males, it is essential to understand the factors affecting HPV vaccine initiation. Previous review studies have reported that race and ethnicity, age, health insurance status, previous vaccination history, personal knowledge and awareness of HPV, and parental knowledge and education levels are significant predictors for HPV vaccination uptake ,16. NeveIncreasing HPV vaccination rates in men requires identifying the unique factors affecting men's HPV vaccine initiation and establishing public health policies accounting for those factors. The Behavioral Model of Health Service Use (BMHSU) offers a multidimensional explanation about a person's use of health services. This study uses the BMHSU to structure the factors influencing HPV vaccination in men and provide a comprehensive understanding of these factors. Therefore, this study aimed to (1) confirm the factors affecting HPV vaccination in men through a systematic review of previous studies and (2) identify which components of the BMHSU were explored and influenced HPV vaccination in men.This study uses the BMHSU developed by Andersen  as a fraThe BMHSU explains that health behaviors can be influenced by individual characteristics and the surrounding environment. In this model, the domain of population characteristics includes predisposing characteristics, enabling resources, and needs. Predisposing characteristics are described as personal propensities reflecting sociodemographic factors , social structure , and beliefs . The enabling resources refer to the means that individuals have available to them, such as insurance, income, and community facilities. The needs refer to personally perceived and evaluated needs. Additionally, the domain of environment includes the health care system and external environment.This study is a systematic review conducted to identify the factors influencing HPV vaccination in men. This study was performed according to the PRISMA  guidelines ; howeverThe data search was performed comprehensively across three electronic databases: PubMed, Embase, and CINAHL complete. Articles from the inception of the databases until July 2020 were searched. We applied search terms according to our research question: “What factors affect men's HPV vaccination uptake?” In accordance with the search terms, the MeSH , Emtree, and free terms were collected from the relevant literature and electronic databases before the search. A keyword search strategy was developed with the following terms: “Papillomavirus Infections,” “Papillomavirus,” “Human Papillomavirus,” “Wart virus,” “HPV,” “Vaccination,” “Vaccine,” “Immunization,” “Male,” “Men,” and “Boy.” The search strategies are given in detail in We set the inclusion criteria for identifying publications in accordance with the purpose of the review, as follows: (1) studies involving heterosexual male participants, (2) availability of HPV vaccine initiation data of the participants, (3) studies reporting factors or predictors associated with the HPV vaccination rate of men, and (4) peer-reviewed articles. The exclusion criteria were as follows: (1) studies presenting data excluding gender classification, (2) gray literature such as conference abstracts, (3) articles not published in English, and (4) articles describing experimental studies. All the articles were cross-checked by the research team.The data were extracted independently by 4 authors . Duplicates were removed first using bibliography software . After removing duplicates, the titles and abstracts were screened using the preset criteria, and irrelevant articles were excluded. A total of 30 studies were finally selected after assessing full-text articles. P values used to identify which influencing factors had been studied and where the evidence was statistically significant were recorded. This information was then integrated to review the effects of different factors across the literature. Then, all the factors identified were grouped reflecting the components of the BMHSU.For synthesis of the extracted data, the included studies were respectively coded using a predesigned template comprising the study authors, year of publication, country of data collection, study type, data source, age of the participants, sample size, and study results. The factors affecting HPV vaccination in men were classified as the key results. Factors were recorded for every association between factors and any corresponding We used the Mixed Methods Appraisal Tool (MMAT) version 2018 for quality assessment of the eligible articles . The MMAA total of 30 studies were included in the review ,18,30-57We adopted Anderson's BMHSU to structure the results of the review and reveal the relationships among the factors identified. We grouped the identified 50 factors into two components of the BMHSU: 47 population characteristics and 3 environmental factors. The factors identified in this review are presented in Population characteristics (47 factors)Predisposing (25 factors)Sociodemographic and social structure factors (13 factors)Race and ethnicityAgeParental education levelSexual orientationNativity statusRelationship and marital statusParental age Parental marital statusEducation levelEmployment statusNumber of children in householdLanguage proficiency of caregivers Parental employment statusBeliefs (12 factors)Parental awareness of HPV vaccineAttitude toward HPV vaccinationAwareness of HPV or HPV vaccinePerceived behavioral controlReceipt of STI informationSearching for health informationSubjective norms about getting HPV vaccineParents’ perceived effectiveness of HPV vaccineParents’ perceived risks of HPV Parental talks with sons about HPV vaccineParental willingness to get sons free HPV vaccine Parents’ perceived severity of HPV-related cancersEnabling (8 factors)Family (4 factors)Household incomeInsurance typeHaving clinics for usual health careCurrent state of insuranceCommunity (4 factors)RegionSize and type of educational institutionMedical accessibilityAvailability of cost-free vaccination programsNeed (14 factors)Perceived (13 factors)Vaccinations other than HPVNumber of visits to clinicsSexual behaviorsTime from the last check-up visitPerceived personal health statusHIV testing historyCheck-up at 11-12 years History of urinary tract infectionsCigarette smokingReasons for clinic visits (preventive or acute)Maternal vaccination for influenzaMaternal STI historyMaternal Pap smear screeningEvaluated (1 factor)Mother’s abnormal Pap smear resultEnvironment (3 factors)Health care system (3 factors)Health care provider’s recommendation for HPV vaccineYear that vaccinations were performedFacility typeAccording to the BMHSU, the domain of population characteristics includes predisposing factors, enabling factors, and need factors.Among the predisposing factors, social structure reflected the social position of the individuals in their society. We combined sociodemographic factors and social structure components of the BMHSU because it may be difficult to distinguish them in different cultural contexts. We then found 13 factors that were categorized as sociodemographic factors and social structure factors, including age, sexual orientation, relationship or marital status, parental age, race or ethnicity, education level, employment status, nativity status, number of children in the household, parental education level, parental marital status, language proficiency of caregivers, and parental employment status. Approximately half of the studies (n=16) explored age as a factor related to the HPV vaccination initiation ,54,55,57We identified 12 belief factors, namely attitude toward HPV vaccination, awareness of HPV or HPV vaccine, perceived behavioral control, receipt of STI information, searching for health information, subjective norms about getting HPV vaccine, parental awareness of HPV vaccine, parents’ perceived effectiveness of HPV vaccine, parents’ perceived risks of HPV, parental talks with sons about HPV vaccine, parental willingness to get sons vaccinated, and parents’ perceived severity of HPV-related cancers. Beliefs refer to individual values about health, attitudes toward health services, or knowledge about disease. Significantly, sons of parents with high awareness of the HPV vaccines were more likely to be vaccinated ,50. HoweWe found four enabling factors that were ultimately categorized as family factors: household income, health insurance types, having clinics for usual health care, and current state of insurance. As for household income, those with low economic status had a higher likelihood of being vaccinated according to 4 studies ,44,45,53The remaining four factors identified were categorized as community factors: region , size and type of educational institution, accessibility to medical facilities, and availability of cost-free vaccination programs. The rate of HPV vaccination was significantly higher in urban areas ,46 whereThe need factors of populations could be classified into perceived and evaluated. In this study, 13 factors were identified as perceived needs that affect HPV vaccination in men, including vaccinations other than HPV, the number of visits to clinics, sexual behaviors, time from the last check-up visit to a clinic, perceived personal health status, history of urinary tract infections, participants’ HIV testing history, check-up at 11 to 12 years , cigarette smoking, reasons for clinic visits, maternal vaccination for influenza, maternal STI history, and maternal Papanicolaou (Pap) smear screening. The reviewed studies reported that men who received other vaccinations  were more likely to take HPV vaccines ,43,44,54In this study, one factor was classified as an evaluated need: the mother’s abnormal Pap smear result. It was found that initiation of HPV vaccination was associated with abnormal maternal Pap smear results .The BMHSU suggests the health care system and external environment as the environmental factors that affect individual health behaviors . This reThis systematic review identified 30 peer-reviewed research articles published from 2013 to 2019 that contained studies analyzing the factors affecting male HPV vaccination. We identified a total of 50 modifiable and nonmodifiable factors across a wide range of domains assessed by the authors of those studies as being associated with male HPV vaccination. For this study, we used Andersen’s BMHSU to structure the identified factors. The highest rates of vaccination tended to be associated with the following identified factors: men aged 10 to 20 years, Hispanic race, adolescents with single parents, higher parental knowledge and awareness of HPV vaccination, low economic status, individuals with public insurance, males living in urban areas, individuals receiving other vaccinations, frequent visits to clinics, and receiving health care providers’ recommendations. Although many factors have been identified in previous studies and could be potential affecting factors , they were often only assessed by single studies featuring small sample sizes, thus limiting the generalizability of these factors to the larger male population.We found that health care providers’ recommendations are major facilitators of HPV vaccinations in men. These findings coincided with those of prior review studies noting that the health care provider’s recommendation was the most significant factor leading to the initiation of HPV vaccination -60. One This review suggests that frequent contact with health care providers is a promising factor for promoting HPV vaccination rates in men. We found that the number of visits to clinics and accessibility to health care facilities have significant relationships with the initiation of HPV vaccinations in men ,38,46,54This review also suggests that parental awareness of HPV vaccination is an essential facilitator of HPV vaccinations in children. Several previous studies on men’s HPV vaccinations have noted that a lack of knowledge regarding the HPV vaccine is one of the causes of low HPV vaccination rates in men -66. RadiIn this study, some factors  were significant but inconsistent in their direction of association with male HPV vaccination. In a study performed in the United States, household income had a negative relationship with HPV vaccination, whereas in a study performed in Denmark, a positive one was found. Regarding ethnic groups, the reviewed studies suggest various ethnic groups to be the most vaccinated, for example, Hispanics or African Americans. One of the reasons is that most of the reviewed studies were conducted in the United States. Since 2011, the United States has included men in the national HPV vaccination program. Accordingly, the HPV vaccination rate in men has changed over time, and it can be expected that the findings are diverse according to the time of the studies included in this review. For more nuanced and conclusive results on these aspects, future research should be performed in a wider range of countries and target families with different socioeconomic statuses and ethnic backgrounds.This review has some limitations. First, most of the included studies, except for 1, were conducted in the United States. Despite the comprehensive findings on the factors affecting male HPV vaccination, it might be difficult to generalize these results. Second, most studies that were reviewed in this work performed secondary data analyses and extracted the variables from available large-scale data sets that had already been constructed for different purposes. Thus, a wide range of psychosocial variables or factors were not reflected in the reviewed studies. Third, we only included heterosexual participants. Men who have sex with men (MSM) are at high risk for HPV infection ,69. HPV This review analyzed 30 research articles using a systematic approach and identified a total of 50 factors affecting HPV vaccination in men. Based on our results, to increase the rates of male HPV vaccination, strategies targeting health care providers should be considered so that health care professionals can provide consistent and evidence-based recommendations for HPV vaccination, including frequent visits or contact with health care providers. In addition, national policies should include parents as decision-makers and increase their knowledge and awareness of HPV vaccination and its effects on preventing a variety of cancers.


The human papillomavirus (HPV) is a DNA virus, which belongs to papillomaviridae family, being of low and high risk, which infect the skin and mucous membranes and can induce benign and malign tumor formation. In the oral mucosa they have been associated with oral papilloma, focal epithelial hyperplasia, leucoplakia and oral neoplasia.to study the frequency of HPV finding in oral mucosa of normal people.Prospective study, cross-sectional cohort. One hundred volunteers, young adults, healthy, aged between 20 and 31 years, university students with no history, no complains, without oral or oropharyngeal lesions. They were submitted to a questionnaire with questions regarding HPV infection epidemiology. The samples were harvested by brushing and analyzed by PCR.The results were negative for HPV in all samples.It seems we had high social and economical class individuals, with nutrition rich in carotenoyds and vitamin C, low smoking and alcohol consumption and heterosexual habits with predominant monogamy and regular use of condoms. Skin and mucosa are the preferential sites infected by the human papillomavirus. HPV is frequently associated with benign and malignant neoplasms in the oral cavity, the most commonly of which being squamous cell carcinoma. The presence of HPV in the epithelium of normal oral mucosae, as reported in the literature, does not allow for accurate inferences regarding the virus' role on carcinogenesis, as to whether it is the main etiologic agent, merely a secondary force, or simply another inhabitant of the oral epithelium. In spite of the improvements introduced to oral mucosa HPV detection techniques, the virus direct involvement in the appearance of oral carcinomas is yet to be definitively provenThe human papillomavirus (HPV) belongs to the papillomaviridae genus, papovaviridae family, and has a double circular DNA strand with approximately 8,000 base pairsHPV cannot infect us through an intact squamous epithelium. In vivo, it infects the basal layer of mitotically active skin or mucosa through abrasions or wounds inflicted upon the epithelium.6Sexual intercourse is the main mode of transmission of HPV.In terms of carcinogenesis, in situ hybridization was performed only to find HPV types 16 and 18 in oral cavity squamous cell carcinomas.Authors looking at changes in eating habits indicated that regular intake of papaya, a fruit rich in carotenoids , and citric fruits (vitamin C) led to a reduction on the persistence of infection by HPVAccording to the literature, prevalence rates of HPV in normal oral mucosae vary substantially. Our survey found values ranging from 0% to 100%19,25–36, as seen on This paper aims to enhance the knowledge on HPV epidemiology and prevalence rates in healthy individuals, so that future studies can determine which protection factors are present in these individuals, which mechanisms are in effect and how the virus participates in the genesis of tumors, so prophylactic and therapeutic measures are developed for the benefit of larger populations.This prospective cross-sectional survey was conducted between May 17, 2006 and April 11, 2007. One-hundred individuals with ages ranging between 20 and 31 years volunteered to participate in this study. Only individuals without previous history, complaints or present macroscopic oral cavity and oropharyngeal lesions were enrolled. All individuals answered a standard unidentified questionnaire numbered based on the collected samples. Epidemiologic factors connected to the transmission and persistence of HPV infection were addressed, such as gender, ethnicity, smoking, alcoholism, use of illicit drugs, sexual habits, number of sex partners, use of condoms, and eating habits specifically related to foods rich in vitamin C (citric fruit) and carotenoids (papaya). After carefully examining the individuals oral cavity and oropharynx using a photophore, samples were collected from the oral mucosa and the mastication sites using an Endobrush® brush. Samples were kept in refrigerated sterilized sealed numbered packages and sent to the Genic Expression Laboratory at the Carlos Chagas Filho Biophysics Institute to be analyzed through PCR (polymerase chain reaction). PCR was done using primers GP5+/GP6+ and MY09/ MY11 added to the DNA samples along with enzyme Taq polymerase, into the reaction compound containing all other components required for DNA synthesis. Then the reaction compound was placed on a thermocycler and submitted to repeated amplification cycles at different temperatures following the reaction phases: denaturation at 94°C, hybridization at 60°C, and synthesis at 72°C. The final product was amplified and analyzed through polyacrylamide gel electrophoresis. All reactions included a negative control  and a positive control (in which a known standard gene was amplified).This study was approved by the Research Ethics Committee at the Clementino Braga Filho University Hospital and registered before the Scientific Research Committee under the following permits: CEP:090/06 and CIC:062/06.Questionnaire results - sample characterization: Forty of the 100 individuals enrolled in our study were males and 60 were females; 86 claimed to be Caucasian, nine were brown and five were black; ages ranged between 20 and 31 years with a mean value of 22.65 years. In terms of tobacco consumption, 97/100 were non-smokers and 3/100 were smokers. Alcohol drinking was described in the following manner: 31/100 claimed not to have any alcohol; 56/100 have alcohol once a week; 3/100 have alcohol twice a week; 6/100 have it three times a week; 4/100 did not respond. Sex habits, as reported: 100/100 claimed to be heterosexuals; 85/100 have only one sex partner; 13/100 have more than one partner; 69/100 have oral sex; 22/100 do not have sex; 9/100 did not respond; 46/100 always wear condoms; 26/100 use condoms sometimes; 20/100 never wear condoms; 8 did not respond. Consumption of citric foods (vitamin C): 47/100 have them once a week; 26/100 have citric foods twice a week; 15/100 three times a week; 2/100 did not respond. Papaya consumption (carotenoids): 29/100 have it once a week; 5/100 twice a week; 5/100 three times a week; 53/100 do not have it; 8/100 did not respond.The questionnaire results on sample characterization can be seen on Table 2. PCR results were negative for all individuals involved.Social-economic factors: anogenital infections by HPV appear to be directly connected to social and economic variables.Eating habits: regular consumption of carotenoids  and vitamin C suggested reduced persistence of HPV infectionSex habits: all subjects in our sample claimed to be heterosexuals . Considering that having multiple partners is a factor more frequently found among homosexuals, one may assume that heterosexuality has contributed to the reduction on the virus prevalence rates in our sample; however, no specific studies on HPV prevalence rates among homosexuals were found. In our sample individuals were mostly monogamists, as 6% (6/100) claimed to have less than one partner per week, 85% (85/100) only one partner per week, 5% (5/100) two to three partners per week, 2% (2/100) more than three partners per week, and 2%(2/100) did not respond. This information is reinforced by our results, as 92% (92/100) of the subjects claimed to have only one partner per week when it comes to kissing the lips of another person. It is known that multiple contacts on one same day is rather common among young people in our society (thus the question was included in the questionnaire). Additionally, we must consider the relevance of the reported use of condoms; 46% (46/100) claimed they always use it, 26% (26/100) use it sometimes. The few individuals - 3% (3/100) - who reported to have sex with three partners per week and claimed not to wear condoms 1% (1/100) or to wear them sometimes - 2% (2/100), also had negative test results for HPV. The predominantly monogamist behavior and of using condoms by the subjects in our sample may have contributed for the absence of HPV positive test results. Although 69% (69/100) of the subjects in our sample stated they had frequent oral sex, considered by some as the principal infection pathway for oral HPV17, many authors believe there is no clear or proven link between oral sex and greater predisposition to acquiring oral HPV infectionImpact of tobacco and alcohol: differently from what was observed in genital cancerThere seems to be a preventive effect of tobacco in oral and oropharyngeal infection by HPV, resulting probably from increases in keratinization of mucosal surfaces, rendering them stronger against minor trauma and less susceptible to HPV basal layer cell infectionOnly 3% (3/100) of the subjects in our sample claimed to be smokers, a fact that certainly did not impact the results reported.For alcohol consumption, 32% (32/100) of the subjects claimed they did not drink, 55% (55/100) said they had it once a week, 3% (3/100) had it twice a week, 6% (6/100) had it three times a week, and 4% (4/100) did not respond. Alcohol consumption was therefore reduced and of little significance. High alcohol consumption patterns seem to work synergistically with high risk HPV infectionTherefore, the impact of tobacco and alcohol consumption upon oral mucosa HPV infection should be further clarified.Persistence of HPV infection and immune aspects: infection by HPV takes place at the beginning of sex life, somewhere between adolescence and early twenties. In most of the cases the infection is transient, and no clinical evidence indicates whether the disease can be suppressed or eliminated at all, unless immune incompetence sets in. Some persistent infections by high-risk virus types may evolve to genital cancer. Most of the time, the disease is diagnosed between the ages of 25 and 29 yearsImpact of diagnostic tool limitation: there still is variation in detection rates, depending on the chosen mucosal sample collection method, namely scrapes, lavages, or biopsy and the elected PCR assayThe existence of local factors, as well as the fact that saliva has components that may have a protective effect such as lysozymes, lactoferrin, IgA, and cytokinesAlthough the fact that virus prevalence rates range between 0% and 100% in normal individuals indicates the possibility that the oral mucosa may work as a reservoir of virusesNo traces of HPV were found in our sample based on the tests performed in our study. The vast variation (0–100%) on HPV prevalence rates found in the oral mucosa of healthy individuals found in the literature may indicate that the methods used to detect the virus need to be reassessed. It is our belief that more studies should be conducted to assist in the development of new methods that introduce new elements to clarify how HPV behaves in oral mucosa infection.


Our aim was to assess the level of knowledge regarding HPV infection among parents, highschool students, medical students and doctors, with an emphasis on their main source of information—the Internet. (2) Methods: We applied five questionnaires to six categories of respondents: parents of pupils in the 6th–8th grades, medical students, doctors, boys in the 11th–12th grades, girls in the 11th–12th grades and their mothers. (3) Results: We included a total of 3108 respondents. 83.83% of all respondents had known about HPV infection. The level of information about HPV infection and vaccination was either satisfactory, poor or very poor. Their main source of information varied depending on the respondent profile and professional activity. Medical students were informed by doctors and healthcare professionals (53.0%), doctors gathered their information from books, journals and specialized brochures (61.6%). For the other categories of respondents, the Internet was the main source of information. Most respondents answered that doctors and healthcare professionals should provide information on HPV infection and vaccination, but very few of them actually seeked information from their general practitioner. (4) Conclusions: Population adherence to the appropriate preventative programs, as well as relevant information disseminated by the medical staff are key elements towards reducing the risk of HPV-associated cancers. An important role could also be played by schools, where teachers and school doctors could provide relevant information on the general aspects of HPV infection. Additionally, sex education classes and parent-teacher meetings should cover the main characteristics of HPV infection and what preventative measures can be employed against it.(1) Background: The infection with Human papilloma virus (HPV) is the most common sexually transmitted infection and it has been associated with cervical cancer (CC) in 99.7% of the cases. In Romania, CC is the second most common, with incidence (22.6% The infection with Human papillomavirus (HPV) is the most common sexually transmitted infection worldwide and it has been associated with cervical cancer (CC) in 99.7% of the cases, thus being considered an important etiological agent ,2. So fa000) and mortality rates (9.6%000) three times higher than in any other European country. Current data shows that every year, 3380 women in Romania are diagnosed with CC and 1805 of them die [CC is the fourth most common type of cancer among women worldwide and in Romania it is the second most common, with incidence rates , which was implemented in 2012 and it addresses women aged 25–64 years who have no symptoms suggestive of CC, a previous diagnosis of CC, or who had undergone total hysterectomy. The test is repeated every 3 years for women aged 25–49 years and every 5 years for women aged 50–64 years [However, the lack of a national cancer registry is a major barrier to reducing CC screening in Romania . AdditioConsequently, by the end of 2010, the programme was discontinued ,15. AnotIn Romania, low HPV vaccine uptake rates is a consequence of low adherence to screening programs for eligible women, lack of parental approval for HPV vaccination, as well as a general lack of education regarding HPV infection and the severity of its consequences .Preferred sources of information that the Romanian population uses are mass-media , healthcare professionals, medical specialty books and brochures, the Internet, parents, relatives and school teachers ,19.The Internet, with a special emphasis on social media platforms, can significantly impact personal awareness, knowledge, attitudes and beliefs regarding HPV infection and vaccination . Dunn etUnderstanding the general population’s personal beliefs regarding HPV vaccination and assessing their level of knowledge on HPV as an etiological agent for CC are inextricably linked to development of an effective health policy supporting HPV vaccination and CC screening programs . PopulatGiven the severity of HPV infection complications, its potential for malignant transformation, its high prevalence and the lack of adherence of the Romanian population to CC screening and HPV vaccination programs, HPV is still a topic of national interest. In the digital age, where access to information is unrestricted, the Internet has become a reliable source of information, sometimes to the detriment of appropriate information sources, such as physicians and medical brochures. Our aim was to assess the level of knowledge about HPV infection among students, adolescents, mothers, parents, and physicians, as well as to reveal their main source of information.The first questionnaire was self-applied to 918 parents of pupils in the 6th–8th grades and it consisted in 34 questions . Three MThe second questionnaire was self-administered to 290 medical students in the 1st and 232 in the 6th year at the University of Medicine, Pharmacy, Science and Technology ‘George Emil Palade’ of Târgu Mureş and it included 55 questions . They weThe third questionnaire was sent online to 1411 doctors from three different medical specialties: 1344 general practitioners, 42 pediatricians and 25 obstetricians/gynecologists. Only 640 responded: 580 general practitioners, 39 pediatricians and 21 gynecologists, with an overall response rate of 43.1% for general practitioners, 92.8% for pediatricians and 84% for gynecologists. It included 38 questions .The fourth questionnaire was distributed among 654 highschool students in the 11th–12th grades from two highschools in Făgăraș City. The questionnaires were partly different among boys and girls and they included 22 and 19 questions, respectively.The fifth questionnaire consisted in 29 questions and it was self-administered to 187 girls in the 11th–12th grades and their mothers. Three High Schools were randomly chosen, two of which from Târgu Mureș and one from Miercurea Ciuc.We conducted a cross-sectional study in which we applied five questionnaires to six categories of respondents: parents of pupils in the 6th–8th grades, medical students, doctors, highschool boys in the 11th–12th grades, highschool girls in the 11th–12th grades and their mothers. Each of the five questionnaires mentioned the purpose of the study and included a data anonymity and confidentiality statement. These questionnaire-based studies were approved by The Ethics Committee of the University of Medicine and Pharmacy of Târgu Mureș (no. 55/13.05.2019). The questions were either open-ended, closed with ordered answers, closed with unordered answers, or binary. The respondents were given 15 min to complete the questionnaires. The questions were focused on the level of knowledge about CC, the preventative role of HPV vaccination, the attitude towards serious disease prevention and their preferred sources of information. The level of knowledge about HPV infection and vaccination was rated on a scale from 1 to 5: 1-very poor, 2-poor, 3-satisfactory, 4-good, 5-very good . The chaData was collected in Excel forms. Statistical analysis was performed using the Statistical Package for Social . Data were labelled as nominal or quantitative variables. Nominal variables were characterized by means of frequencies.We included a total of 3108 respondents, of which 918 were parents of pupils in the 6th–8th grades, 290 1st year and 232 6th year medical students, 640 doctors, 354 boys in the 11th–12th grades, 487 girls in the 11th–12th grades and 187 of their mothers.83.8% of all respondents had known about HPV infection, of which 85.8% parents of pupils in the 6th–8th grades, 89.7% medical students, 100% doctors, 70.4% boys in the 11th–12th grades, 74.3% girls in the 11th-12th grades and 82.8% of their mothers. The level of information about HPV infection was satisfactory for almost half of the doctors (47.3%), this level being identified in around one third of most respondents except for girls, of whom 32.4% and 24.8% had a poor and a very poor level of information, respectively. A good level of information was identified in 32.1% doctors and 28.9% medical students. The degree of information on HPV vaccination was satisfactory for 44.6% doctors, while for the other categories of respondents the poor level of information was predominant .Regarding the optimal age for HPV vaccine administration, 69.0% of the medical students, 72.3% doctors and 30.9% boys in the 11th–12th grades considered that optimal vaccination should occur between 12–14 years, while 44.5% of the parents of pupils in the 6th–8th grades and 50.6% of the mothers of high-school students in the 11th–12th grades believed that vaccination should be considered after the age of 18 years. 50.6% girls in the 11th–12th grades believed that vaccination should be administered before becoming sexually active.The majority of respondents believed that HPV infection could not be transmitted if they used a condom: 60.8% of parents of pupils in the 6th–8th grades, 73% medical students, 92.9% doctors, 50.5% boys in the 11th–12th grades, 64.7% girls in the 11th–12th grades and 55.7% of their mothers. Medical students and doctors believed that HPV infection could be prevented by resuming sexual activity to one sexual partner or by HPV vaccination, with a frequency of 68.1% versus 70.5% and 63.7% versus 86.6%, respectively. Also, 49.5% of girls in the 11th–12th grades and 52.3% of their mothers believed that vaccination was an effective measure to prevent HPV infection.The main source of information on HPV infection varied depending on the profile of the respondent and their professional activity. Medical students preferred to be informed by doctors and healthcare professionals (53.0%), as well as by using the Internet (47.4%). Doctors would rather get updates from books, journals and medical brochures (61.6%) and from the Internet (46.4%). For the other categories of respondents, the Internet was the main source of information: 42.9% parents of pupils in the 6th–8th grades, 58.6% boys in the 11th–12th grades, 78.3% girls in the 11th–12th grades and 55.7% of their mothers.When asked who would be more suitable to provide information about HPV infection or vaccination, the majority of the respondents preferred doctors or healthcare professionals . HoweverHuman Papilloma Virus is estimated to affect approximately 50–80% of sexually active women and men throughout their lifetime. Studies have shown that infection with HPV types 16, 18, 31, 33, 35, 45, 52,58 have an increased risk of malignant transformation in both males and females . In EuroAccording to the World Health Organization, most countries recommend vaccination against HPV at the age of 9–12 years, the main target group being adolescent girls. This outdated focus on women vaccination might explain the gender gap in HPV education . Hence, Until 2021, in Romania, HPV vaccination was administered free of charge exclusively to girls aged 11–14 years. The Ministry of Health has since extended the target group to girls aged 14–18 years, which is in line with the Epidemiology and Oncology Commissions of the Ministry of Health and the National Institute of Public Health recommendations .From the records of our study, 69.0% medical students and 72.3% doctors answered that the optimal vaccination age against HPV infection was between 12 and 14 years. The majority of the girls surveyed (50.6%) considered vaccination to be appropriate before becoming sexually active and 44.5% parents of pupils in the 6th–8th grades and 50.6% of the highschool student’ mothers answered that vaccination should be administered after the age of 18 years.So far, studies at European level have shown that adolescents have a low level of knowledge regarding HPV infection and vaccination . One metThe importance of information sources on HPV infection has been demonstrated through numerous studies which showed that individuals gathering information from the Internet had a higher level of knowledge and were more likely to accept HPV vaccine ,31. HealSocial networks  have become an increasingly popular source of medical information for people around the world. They democratize the ability of both physicians and non-healthcare professionals to share their experiences and opinions on medical issues to a wide audience, irrespective of the medical accuracy of their information. The alarmingly rapid dissemination of inaccurate, medically biased information about health issues on social networks poses a great threat to the general population, who cannot discern between authentic and false information ,37,38,39The medical advice given to parents plays an important part in the decision to vaccinate their children, especially information regarding the safety and efficacy of the vaccine ,41. AlsoConsidering that Romania ranks second in Europe with a critically high number of deaths from CC, it can be argued that there is a major lack of education about HPV infection, its role in CC development and HPV vaccination as a preventative method, which is in agreement with our findings. Additionally, information campaigns exclusively targeting women has lead to a complete disregard of representatives of the opposite sex. Lack of adherence to screening programs and parental opposition indicate low levels of education about HPV infection and its long-term implications. This makes HPV infection a matter of national interest, with a major impact on the morbidity and mortality of both Romanian men and women.One major limitation of our study is given by the assessment of the population from one country alone, without prior application of a probabilistic sampling formula, thus influencing the generalization of the results. However, the large sample size, high response rates and the heterogeneity of socio-demographic background of the respondents tackle this vulnerability. Another limitation derives from the completion method of the questionnaires, which were self-administered and might bring into question the level of comprehension of the respondents and thus, the reliability of their answers. We reduced this limitation by excluding both incomplete and invalid questionnaires, after thorough internal validity assessments. The questionnaires applied to physicians had unsatisfactory low response rates, of 43.1% for family doctors, which might be explained by either the online completion method or the reluctance of the respondents, even though anonymity and confidentiality were respected. The questions we applied were rather subjective and did not address specific information regarding HPV infection and HPV vaccination.In our study, most respondents gathered their information about HPV infection and vaccination from Internet sources and their level of knowledge was self-assessed as either satisfactory or poor. Very few respondents seeked information from their general practitioner or HPV specialist, at the same time considering that accurate information about HPV should be provided by physicians and healthcare professionals. In order to reduce the risk of HPV-associated cancers, populational adherence to screening programs and dissemination of relevant information by medical staff are key elements.Vaccination information campaigns and screening programs are effective ways to reduce the incidence, mortality and morbidity associated with HPV infection. Teenager and young adult education on HPV could make them more sexually responsible, which might also determine them to get vaccinated. An important role could also be played by schools, where biology teachers, class masters and school doctors could provide relevant information on the general aspects of HPV infection. Additionally, sex education classes could be held by a mixed team of medical specialists and psychologists, covering sexual health topics like HPV infection and vaccination, as well as other sexually transmitted infections prevention. Equally important are the parent-teacher meetings discussing the importance of HPV vaccination and any other concerns that parents might have regarding the vaccine.


Of the HPV16-positive cases, cobas® 4800 and REBA HPV-ID® identified 28.81% (51) and 25.42% (45) of the CIN1 cases, and 55% (33) and 50% (30) of the 60 CIN2/3 cases, respectively. HPV-diagnostic concordance was 82.17% overall (kappa = 0.488), 87.45% for HR-HPVs (kappa = 0.689), and 88.33% for CIN2/3 (kappa = 0.51). The HR-HPVs detection rates of these assays were comparable. Our findings reveal that the FDA-approved HR-HPVs detection assay is appropriate for screening women with HR-HPVs infection, and for predicting increased risk of cervical cancer progression. REBA HPV-ID® can be used to detect low risk-HPV types in high-grade cervical lesions that are HR-HPV negative as well as in the distribution of HPV types.Persistent infection with high-risk human papillomaviruses (HR-HPVs), particularly HPV16 and 18, has long been known to induce cervical cancer progression. However, given that a minority of HPV-infected women develop cancer, analysis of HR-HPV-infected women could help to predict who is at risk of acquiring cervical cancer. Therefore, to improve HR-HPVs detection, we used the FDA-approved cobas Cervical cancer is the fourth most common cancer among women worldwide, with more than half a million estimated new cases and 311,365 deaths in 2018 (GLOBOCAN) . HR-HPV3The conventional Pap smear has been used for cervical cancer screening for more than 50 years , with a Given the high prevalence of HR-HPVs in cervical cancer, HR-HPV-DNA testing has been introduced as an additional test, in combination with cytology analysis, to screen women who need further colposcopy examination. HR-HPV testing reportedly provided more sensitive CIN2+ diagnosis than cytology ,13. HPV Although various HPV-DNA detection tests exist, the five US Food and Drug Administration (US FDA)-approved assays detect only the HR-HPV types ,19. It h® 4800, Hybrid Capture 2 (HC2) and three others [® 4800 to the HC2 assay, revealing good concordance [® 4800 assay showed higher sensitivity, specificity, and reproducibility than the HC2 assay [® 4800 has been implemented for cervical cancer screening in many countries [® assay developed an automated machine for the hybridization step; however, DNA extraction and PCR amplification steps were performed manually. Therefore, HR-HPVs detection of REBA HPV-ID® assay was evaluated. We compared the FDA-approved real-time-PCR-based cobas® 4800 assay, which can detect 14 HR-HPV types including HPV16, 18 and additional 12 HR-HPV types, with the reverse line blot hybridization-based assay REBA HPV-ID®, which can detect both HR- and LR-HPV. We further compared the diagnosis rates of CIN2/3 lesions. The US FDA-approved HPV-DNA detection assays include cobase others ,19. Mostcordance ,25,26,27C2 assay . Owing tountries ,30,31. Tountries . The REB® 4800 HPV and REBA HPV-ID® assays. The HPV-DNA results were compared to histology diagnoses. The study was approved by the Institutional Review Board (IRB) of Faculty of Medicine, Chulalongkorn University (COA No. 278/2019). Cervical cell samples, collected from 303 women at the King Chulalongkorn Memorial Hospital , were used for HPV-DNA detection and genotyping using the cobas® 4800 HPV assay  for HPV detection and genotyping. The assay can detect HPV16, HPV18, and the pooled presence of twelve other HR-HPVs . The reaction uses a β-globin-primer set as a genomic DNA control to ensure sample quantity and quality. In terms of sensitivity, the limits-of-detection for each HPV type per ml of the original sample were as follows: HPV16 were 85.0% for 150 copies per ml and 100% for 300 copies per ml; for HPV18, these were 93.2% for 300 copies per ml and 100% for 600 copies per ml [Lactobacillus species, Neisseria species, Staphylococcus species, Chlamydia trachomatis and Gardnerella vaginalis, fungi such as Candida albicans, viruses such as HSV1, HSV2, CMV and EBV, and other LR-HPV types such as, HPV6 and HPV11. These indicated that the cobas® 4800 assay specifically detects only HPV16,18 and other 12 HR-HPVs. The limit of detection and the analytical specificity written in the manuscript were determined by the manufacturer.We used the fully-automated real-time PCR-based cobas® assay . REBA can identify 32 HPV types: 18 HR types , 1 probable HR type (HPV34), and 13 LR types . The membrane strip hybridization control line verifies the chromogenic reaction and the presence of the reagents; the negative control line checks for contamination; and the β-globin positive control line verifies the successful PCR amplification and quality of collected samples. The distribution of HPV types was evaluated using the REBA HPV-ID® system. The limits of detection were 100 to 1000 copies per PCR reaction (50 μL). There was no cross-reactivity between HPV types. The limit of detection and the analytical specificity were determined by the manufacturer.We conducted HPV genotyping as per the manufacturer’s instructions. Briefly, extracted DNA was amplified in a 50 μL PCR reaction volume . We ran the positive control (HPV33-positive) and negative control provided with the kit in parallel. The PCR conditions were as follows: initial denaturing at 94 °C for 5 min, followed by 15 cycles of 94 °C for 30 s, 55 °C for 30 s, followed by 45 cycles of 94 °C for 30 s, 52 °C for 30 s, and 72 °C for 10 min. The PCR condition was similar to the previous report with some modifications . HPV gen® 4800 and REBA HPV-ID® HPV assays using the kappa statistic, which ranges from 0 to 1: <0.20, poor; 0.21–0.40, weak; 0.41–0.60, moderate; 0.61–0.80, good; and 0.81–1.00, very good. Two-sided p-values were calculated via McNemar’s chi-square (p < 0.05).Statistical analysis was performed using SPSS for Windows 22.0 . We evaluated HPV genotyping concordance between the cobasHPV-DNA genotyping and histological investigation were performed on 303 cervical cell and colposcopy tissue samples, respectively. Histological examination revealed that 177 (58.4%) were positive for cervical intraepithelial neoplasia 1 (CIN1), 14 (4.6%) for CIN2, and 46 (15.2%) for CIN3, with 66 (20.8%) cases of other conditions, namely vaginal intraepithelial neoplasia, chronic cervicitis, benign squamous epithelium, and condyloma acuminata. The average age of the women was 40.76 ± 12.196 years . ® 4800 and REBA HPV-ID® identified 72.27% (219) and 71.62% (217) HR-HPV positive cases, respectively. Of the 303 cases, cobas® 4800 and REBA HPV-ID®, respectively, identified 71.19% (126) and 70.06% (124) of the 177 CIN1 cases; 100% (14) and 92.86% (13) of the 14 CIN2 cases; 78.26% (36) and 86.96% (40) of the 46 CIN3 cases; and 65.15% (43) and 60.60% (40) of the 66 non-CIN  cases  cases . The REB® 4800 and REBA HPV-ID® assay, respectively, identified HPV16 infection in 35.64% (108) and 30.69% (93) of the 303 cases. Of the HPV16-positive cases, the detection rates were lowest for the CIN1 cases , highest for CIN2 , and intermediate for CIN3  (The cobasctively) .® were HPV6, 11, 32, 42, 43, 54, 70, 72, 81, 84 and 87.Of the LR-HPV types, the majority were found either in CIN1 , or other abnormalities  but less frequently found in CIN2/3  . The LR-p = 0.112; concordance rate, 87.45%; kappa = 0.689). For all HPV-positive cases, the assays differed significantly (p = 0.005), because cobas® 4800 does not detect LR-HPV types  was utilized in the present study to detect both HR-and LR-HPVs; additionally, the hybridization step could be performed using an automated machine. In terms of performance capacity, the automated cobas® 4800 assay can complete 96 tests, including 94 clinical samples and 2 controls, in roughly five hours. While, 48 samples can be run through the REBA HPV-ID® assay in about 6 hours, the DNA extraction, PCR amplification, and automated hybridization were done separately. Prior to PCR amplification, samples could be conveniently prepared by adding lysis buffer and boiling [® assay, we compared an US-FDA-approved real-time PCR-based method that detects only HR-HPVs (cobas® 4800), and a reverse line blot hybridization-based assay (REBA HPV-ID®) that detects both LR- and HR-HPVs. Because of this difference in their detection ability, the assays differed significantly in detecting HPV-positive cases. The differences we observed verify that there was no cross-reactivity  by the cobas® 4800 assay, which is consistent with a previous report [For more than 50 years, cervical cancer screening has been done using cytology or Pap smear . Women wl cancer . The cob lesions ,21,42. M HR-HPVs . To dete boiling ,43. To es report .® 4800 than REBA HPV-ID®, consistent with prior findings [® 4800 assay showed high sensitivity for CIN2+ detection, relative to prior cytology results [® assay have used samples with cytologically confirmed lesions [The assays showed a strong concordance for HR-HPV detection, although for CIN2/3-positive cases, the small sample size (n = 60) resulted in a low kappa value. Single or mixed HPV16 infections were detected better by cobasfindings ,44,45. T results ,42. To t lesions ,46.® assay identified the following CIN2/3-positive HR-HPV types: HPV16, 18, 31, 33, 51, 52, 56, 58, 66, 59, and 68, which is similar with the previous study [® assay. LR-HPV types cause benign proliferative lesions such as genital warts, as well as recurrent respiratory papillomatosis (RRP), and is not frequently found in cervical cancer [For the HPV16 type, mostly detected in CIN2/3 cases, with lower detection rates for CIN1 and other abnormality cases, consistent with earlier investigations ,48,49,50us study . If LR-Hl cancer .® assay can be used in the HPV types distribution for epidemiological studies.In conclusion, our findings show that the clinically evaluated US-FDA-approved HR-HPV detection assay could better detect an HPV16 infection and is appropriate for screening women with persistent HR-HPV infections, and for predicting the increased risk of cervical cancer progression. The REBA HPV-ID