Two major drawbacks of the present cervical cancer screening programme in Sri Lanka are, the suboptimal sensitivity of the pap smear and the low coverage. The sensitivity of the HPV/DNA screening test is high. The objective of the study was to explore the acceptability relevance and simplicity of the new HPV/DNA screening implementation among ever-married women in a district of Sri Lanka.Focus group discussions (FGD) (n = 3) in the public health divisions of the Kalutara district were used to collect data during December 2018. The study population comprised of ever-married women 35 years old, who, carried out an HPV/DNA test at a community Well Woman Clinics (WWCs) (n = 89). A list of WWCs was prepared according to an alphabetical order under urban, rural, and estate sector categories and allocated a number. One WWC was selected from each sector randomly for the three FGDs representing the estate, rural, and urban clinics. A convenient sampling technique was used to select participants for each FGD (n = 8). The information collected at each interview was summarized at the end of each interview. The analysis was done with manual content.Most of the participants were Sinhalese , Buddhist , and non-working . The community awareness of HPV/DNA screening and field staff performance were highly appreciated by most of the participants. Most were aware of the high sensitivity of the HPV/DNA test, therefore the early detection rate of cervical cancer precursors is high. Most of the participants expressed the HPV/DNA test as a convenient and neutral test. Most were mentioned the necessity of repeated clinic visits for the pap test and colposcopy in HPV/DNA screened positive follow-up but there was marked acceptability  for HPV/DNA test.Acceptability of the new HPV/DNA screening test was high. Most of the participants perceived the HPV/DNA test to be simple and also relevant. Therefore, the HPV/DNA screening test can be recommended to be incorporated into the National Cervical Cancer Screening Programme as its suitability was well explored in the Sri Lankan setting.The online version contains supplementary material available at 10.1186/s12905-022-01712-2. Cervical cancers are virtually associated with Human papillomavirus infection (HPV). Human papillomavirus infection is exclusively sexually transmitted. Nearly 60 different types of HPV serotypes are known to infect the human genital tract including the cervix uteri . Some onPersistent carcinogenic HPV infection may progress into cervical precancerous lesions  within 10–20 years. The mean age of marriage for Sri Lankan females is 23.9 years . TherefoCofactors favouring HPV infection are not well defined and the following risk factors probably play a role; type of the HPV and its oncogenicity, commencement of sexual activity at an early age, multiple sexual partners, a partner who participates in high-risk sexual activities, immune suppression acquired or primary, poor socio-economic status-poor hygiene and connection with other sexually transmitted agents. Co-factors that precipitate HPV infection to persist are; high parity, tobacco smoking, poor nutritional status, prolonged usage of oral contraceptive pills  . Nobody, she does her work slowly" .One expressed chemotherapy as the key challenge for a patient under treatment for cervical cancer by the following quote:"I exactly can't remember the number of deaths due to cervical cancer in last year… but it says still it's high…" .Some discussants mentioned that deaths due to cervical cancers are high in Sri Lanka. This was captured this way:"You can see clearly, irrespective of the development of treatment facilities…deaths due to cervical cancer remain stable for a long duration of years...access for treatment centres and treatment cost plays important role in this regard" .(ii)Human papillomavirus infection, and cervical cancerTwo study participants admitted that deaths due to cervical cancer remain stable for a long duration. The place to seek treatment is also related to the financial situation of the women. This was how one of the participants presented it:"I got to know effects related to HPV infection, carcinogenic and non-carcinogenic…all cervical cancers are virtually associated with…HPV infection" .Most of the participants gained knowledge on the effects of HPV infection and its association with cervical cancer following the community awareness sessions carried out in the district. A participant admitted in her words: "I never knew that there is a virus called HPV…Which has a cervical cancer carcinogenic effect…I heard that HPV infection as an initial cervical cancer stage…[precursor], Which could be detected by screening" .From the views of the few discussants, they were the first time heard about the HPV virus and HPV infection as a cervical cancer precursor. A participant had this to say:"There are highly carcinogenic virus types too… I have explained the variety of high-risk HPV serotypes, It was around 15…. I can't remember all but HPV types 16 and 18 are contributed to 70% of cervical cancer cases…" .One indicated some serotypes of HPV are more carcinogenic than others and the contribution of HPV serotypes 16 and 18 to cervical cancer is high among all high-risk carcinogenic HPV serotypes and this was pointed out this way:"I came to do screening test for HPV/DNA on the given appointment date…I've noticed in the clinic, informative posters were hanging on clinic walls…It says… HPV infection is exclusively sexually transmitted…" .Among participants, most stated the mode of transmission of HPV is exclusively sexual. One of the discussants captured it this way:"There are some primary preventive methods for cervicovaginal HPV infection in Sri Lanka, condoms during a sexual relationship, and recently introduced vaccines…" .From the views of some study participants, primary preventive methods for cervicovaginal HPV infection are readily available in Sri Lanka. Fortunately, their understanding of preventive measures is great. One said:"It says high-risk carcinogenic HPV infection may progress into cervical cancer after about 10 to 15 years [persistent infection]…" .(iii)Pap test and HPV/DNA test as a cervical cancer screening methodFew discussants noted persistent HPV infection may lead to cervical cancer. One of the participants remarks:"My one of the closest friends had some clinical signs and symptoms…She had undergone repeated pap tests for cervical cancer screening as requested by the Gynecologist. First pap smear, she has done at a MOH area WWC…and repeated ones at hospital WWC" .Most of the study participants stated that the pap test is a National Cervical Cancer screening method in Sri Lanka and they knew that it can be done at either the MOH office level or hospital WWCs. This was captured this way:"I recently went to do my first pap screening test, The biggest problem of the pap test is…missing lesions...[suboptimal sensitivity]. Many chances to miss cervical abnormalities by a pap test only…" .For some, suboptimal sensitivity of the pap test was a priority. Therefore missing many cervical precancerous lesions is unavoidable. One of the participants expressed it this way:"I was asked to attend WWC for a pap test in the middle of this year by the area PHM…I did it so “My pap report received only after 6wks…luckily it was normal… [No Intraepithelial Malignancy]". .Few discussants mentioned they would get the pap report with a lag period time. This was presented this way:"My pap report was normal….nothing else to be done, only routine follow-up after 5 years…" .One participant indicated that the routine screening interval of the pap test is once in every 5 years and shared her experience this way:"It is wonderful to have such an advanced screening test with high detection rate…[sensitivity] as cervical cancer is one of the commonest cancer among Sri Lankan females…" .From the views of most of the participants HPV/DNA test is an advanced screening test to detect cervical precancerous lesions as its sensitivity is high. According to one participant:"HPV/DNA screening test is a cobas 4800 machine screened test…[accurate]. Screening never depends on any individual. I can't explain the variability that might occur in screenings based on personals [cytology]…" .Some participants relied more on the higher accuracy of the HPV/DNA test due to cobas 4800 machine screening report. One of the participants remarked:"I was at a community awareness session in the district…It was explained that HPV is one of the earliest stages that can be identified as a cervical cancer precursor. HPV/DNA test detects the presence of HPV virus in the smear…" .The HPV/DNA test detects the initial precursor before the cervical lesion development was, expressed by most of the participants. A participant described her experience this way:"It was such an opportunity to screen for cervical cancer free of charge...such an advanced test…I am not well aware of the exact cost of the test, but it says it is expensive…much more expensive than a pap test" .Few participants greatly appreciated getting of such an advanced screening test free of charge in the Government sector to reduce the burden of cervical cancer in Sri Lanka. A participant shared her experience this way:"After passing one week following the test…My area PHM informed me that my test report can be collected, I did it…" .iv.HPV/DNA test specimen collection procedure and screening implementationThe advantage of getting a quick test report was mentioned by two participants and this was pointed out this way:"I've undergone a pap test early in this year at a community WWC, It is very similar to the pap test…Specimen collection was done by using a broom-like device, instead of the wooden spatula in the pap test, and then putting it into a liquid container. Push the broom-like device against the bottom of the vial 10 times, forcing the bristles to bend apart. Swirl the broom vigorously after pushing…simple and convenient, I thought it is painful, but the specimen collection was without any pain[neutral]" .Most of the participants perceived an HPV/DNA screening test as a convenient and neutral test by their experience after exposure to the specimen collection at WWCs. A participant shared her experience this way:"I was really afraid to undergo HPV/DNA screening, but It is an easy and comfortable test…" .HPV/DNA test is perceived as an easy test by some participants. According to one participant:"…for me, It was such a quick test, but I exactly couldn't calculate the time spent on the procedure, may be around 15 min…" .Few discussants noted that the HPV/DNA test is a quick one. One said:"I got to know information regarding this new screening test from the community awareness programme held at our MOH area, and leaflets were distributed among participants there…Lectures and discussions were carried out. I've seen an informative poster in all three languages, containing important details regarding HPV infection…Participants asked questions, and cleared doubts…I am so lucky, I got an opportunity to clarify doubts from my area PHM…after I got selected for a free HPV/DNA test…She visited me twice to make me aware…to reduce the anxiety…" .Well-organized community awareness and field staff performance for the new HPV/DNA test implementation was highly appreciated by most of the participants. A participant admitted in her words:"Unlike the pap test, I doubted how this new test is being carried out in our clinic setup… I have noticed the clinic appointment schedule is displayed on the wall, a few more specific items were available at the clinic…If you go to a clinic, in addition to normal WWC clinic items, you can see unopen test kits, special marker pens to write the identification numbers are also available there…" .Some were satisfied with the clinic facilities and clinic staff’s performance in implementing HPV/DNA screening test. One of the participants shared her experience this way:"That clinic day, I was the last person…and I noticed at the end of clinic session…all brushes, which were used to obtain specimen was disposed to a sharp bin, clinic environment was so clean and clear…" .xxii.HPV/DNA screen positive follow-up with pap test and colposcopySharp bins to discard clinical wastes are available at clinic premises. The environment following a clinic session was exemplified by the following quote:"I was informed HPV/DNA screen positive results by MOH….I was called up at the MOH office…MOH personally handed over my report…[anxiety]. It was explained that all HPV/DNA screen positives are not associated with cervical cancer…only need to undergo a pap test within the next 6 weeks…to reassure"  "if the pap test is negative,…then to repeat an HPV/DNA test after 1 year…When the pap test is positive,…Then to be subjected to a colposcopy within one month after the test[to exclude cervical lesion]. Colposcopy is the gold standard test to diagnose cervical lesions as I heard" .Most discussants admitted the necessity of repeated clinic visits for a pap test and colposcopy in HPV/DNA screen positive follow-up as exemplified by the following two quotes:"I would be happy to do all relevant follow-up tests…related to HPV/DNA test, despite I have to go for repeated clinic visits …as I would say it’s an advanced cervical cancer screening method, with a high detection rate of early stages of cervical cancer[precursor]. Therefore it reduces the burden of morbidity, treatment cost, and mortality of cervical cancer" .(vi)Challenges associated with HPV/DNA screeningFor some discussants, irrespective of the repeated clinic visits HPV/DNA screen positive follow-up is very useful. It significantly reduced the cervical cancer burden in Sri Lanka due to the early detection of cervical cancer precursors. This was presented this way:"I went to the WWC on the scheduled day, I was informed the specimen is collected by using a brush… the First time I've seen the brush at the clinic day only...It’s actually like a broom" .All of the participants had seen the specimen collection brush only on the day of specimen collection in the WWC. One participant shared her experience as follows:"I was really scared [hurting myself] of participating in HPV/DNA screening… as I thought the specimen collection is very painful, there is no pain, only a tingling sensation, nothing else…" .Fear of hurting themselves was the biggest barrier associated with the HPV/DNA screening. Further, some thought even HPV/DNA specimen collection is very painful. One of the participants presented it this way:"We were shown some videos of HPV/DNA specimen collection during the community awareness sessions in the district, I was wondering how such a different screening test could be able to correctly administer by our staff suddenly…" .Some participants doubted whether this test is administered correctly by the health staff. One participant described her experience this way:"I got to know that well-organized staff training under expertise was conducted at district level on HPV/DNA specimen collection and screening…" .Prior conduction of well-organized staff training for HPV/DNA specimen collection and training was very useful to raise the community participation in the study. This was presented this way:"Staff may not adhere to screening norms…need continuous monitoring and supervision of HPV/DNA specimen collection and screening". .Two participants pointed out that continuous monitoring and supervision of this new HPV/DNA screening implementation is essential to assure the standards. One of the discussants captured it this way:"I know how difficult to implement a new test…many issues need to be sorted out…It is essential to conduct periodical reviews with expertise…" .One said issues arising in test implementation must be discussed with expertise periodically as exemplified by the following quote:There was marked acceptability among participants  for HPV/DNA screening tests to be incorporated into the National Cervical Cancer Screening Programme in Sri Lank as a primary cervical cancer screening method, irrespective of all difficulties in repeated clinic visits for a pap test and colposcopy in the screen-positive follow-up.Cervical cancer is the second most commonest female cancer in Sri Lanka . TherefoBased on the results of existing studies, many countries are recommending and implementing HPV/DNA testing-based screening programmes. Before implementing HPV/DNA screening test into a National Cervical Cancer Screening programme in a country, the need to understand factors, which will impact the acceptability of HPV/DNA screening test  by a woman is very crucial to ensure the smooth implementation of HPV/DNA test. The present study indicates the knowledge and attitudes of women related to the National Cervical Cancer Screening programme were adequate to decide on the new HPV/DNA test.Mixed method research synthesis categorized relevant factors related to HPV/DNA primary screening for cervical cancer and described their influence on women's acceptability of HPV/DNA testing . ResultsThe direction of influence of psychosocial factors on HPV/DNA test acceptability was formed based on 14 quantitative studies. These influences were such as; facilitators (e.g. HPV/DNA test benefits), barriers , contradictory history , and impact of HPV/DNA screening (e.g. high perceived severity of HPV infection). In the present study, community awareness was done before conducting the study on the benefits of HPV/DNA screening, which may have led to the higher acceptability of HPV/DNA test among women screened.There was a marked elevation in the prevalence of cervicovaginal HPV infection from 2009 3.3%) [.3% [3] tAs mentioned in some other studies challenges for the HPV/DNA screening were identified as difficulties of repeated clinic visits in HPV/DNA screen positive follow-up , 25. SomThis study was restricted to one district out of 25 districts in Sri Lanka due to logistic constraints. Women who had undergone HPV/DNA test were selected for FGDs as they only can give perceptions of acceptability, relevance, and simplicity of new HPV/DNA tests with their experience. The initial HPV/DNA test feasibility study was conducted in the Kalutara district, therefore FGDs were conducted among women who carried out an HPV/DNA test in the same Kalutara district. The population characteristics and the public health infrastructure of the district favoured the generalizability of the research findings to the whole country.Comparison of screening results between vaginal and cervical (gold standard) methods of HPV/DNA specimen collection needs to be carried out to improve the coverage of cervical cancer screening programme as vaginal specimen collection doesn't require speculum insertion, therefore primary health care workers also can collect HPV/DNA specimen, while during their home visits.Implementation of HPV/DNA screening in the National cervical cancer screening programme in Sri Lanka will improve the quality of the programme as the sensitivity of the HPV/DNA test is high. Therefore incidence, morbidity, and mortality of the cervical cancer burden will ultimately be reduced in the country.The present study has revealed the high acceptability of the HPV/DNA screening test among 35 years age cohort of ever-married women and the relevance and simplicity of the test were high as perceived by them. Therefore, HPV/DNA screening test as a primary cervical cancer screening method is recommended to be incorporated into the National Cervical Cancer Screening Programme in Sri Lanka among 35 year age cohort of ever-married women as the prevalence of HPV infection and feasibility of new HPV/DNA screening implementation was well assessed in Sri Lankan setting.Additional file 1. A Moderator Guide for Focus Group Discussion.


Most oropharyngeal and anogenital cancers are caused by human papillomavirus (HPV). Although HPV vaccines showed high efficacy against oropharyngeal and anogenital HPV infections, and cancer precursors in randomized clinical trials, there are limited data on the effectiveness of HPV vaccination against HPV-related cancers. We aimed to evaluate the association of HPV vaccination with HPV-related cancers among a nationally representative sample of United States adults, aged 20–59 years. In a cross-sectional study combining four cycles from the National Health and Nutrition Examination Survey, from 2011 through 2018, we used a survey-weighted logistic regression model, propensity score matching and multiple imputations by chained equations to explore the association of HPV vaccination with HPV-related cancers. Among 9891 participants, we did not find an association of HPV vaccination with HPV-related cancers . Despite no statistically significant association between HPV vaccination and HPV-related cancers, our study findings suggest that HPV-vaccinated adults might have lower odds of developing HPV-related cancers than those who were not vaccinated. Given the importance of determining the impact of vaccination on HPV-related cancers, there is a need to conduct future research by linking cancer registry data with vaccination records, to obtain more robust results. Oropharyngeal cancers, including cancers of the lip, oral cavity, pharynx, and larynx, and anogenital cancers, such as cervical, vaginal, vulvar, penile and anal cancers, are common cancers worldwide . The AmeThere are highly efficacious HPV vaccines against the high-risk HPV infection types, recommended at the age of 9–14 for girls and boys . The AdvGiven the limited literature and high vaccine hesitancy rates in eligible U.S. adolescents ,23, therIn the cross-sectional study, we analyzed four cycles (2011–2018) from NHANES, a continuous survey designed to assess health and dietary status of the non-institutionalized U.S. population . Bi-annuOverall, 39,156 participants responded to health and dietary questions from the four NHANES cycles . 24,222 Two survey questions were used to develop the binary outcome variable: a self-reported diagnosis of HPV-related cancers. The first question was: “Have you ever been told by a doctor or other health professional that you had cancer or a malignancy of any kind?” . The secThe primary exposure variable was HPV vaccination history. It was directly obtained from the survey question: “Have you ever received one or more doses of the HPV vaccine?” . Those pBased on previous literature and epidemiological reasoning, the following covariates were considered as potential confounders of the association of HPV vaccination history with HNGC: age ,30,31, ep-value less than 0.05 was considered a statistically significant finding.To account for the complex sampling design, survey weights, strata and clusters were used in analyzing data. Survey weights were divided by 4 to account for combining four NHANES cycles. In the descriptive analysis, categorical variables were presented as sample frequencies, while percentages were presented as weighted estimates for the target population. Associations between categorical variables and the outcome variable were tested using Rao-Scott chi-square test for complex survey design studies . A surveAdditionally, we performed propensity score-matched analysis to test the robustness of the results; this is considered a secondary confounding adjustment approach to the conventional logistic regression analysis when there are fewer events per confounder . PropensWhile the complete case analysis was more a conservative approach to address missing or invalid responses in covariates, the analysis actually excluded more than 4000 participants. We could not assume that the data was missing completely at random because distributions of sociodemographic characteristics of the study participants—including sex, ethnicity, whether individuals were born in the U.S. or not, income, smoking history, and physical activity—differed between the complete case dataset and the dataset with missing values . Assuminp < 0.05) between 2011 and 2018. 76.8% of all HPV vaccinated participants were in the age group 20–29 years (p < 0.01) (p = 0.001), sex (p < 0.001), education (p < 0.01), ethnicity (p = 0.01), household income (p = 0.001), having smoked at least 100 cigarettes over their lifetime p < 0.001), and routine access to healthcare services (p < 0.01).Overall, 0.7% (72/9891) participants reported being diagnosed with HPV-related cancers in the complete case sample . Sixy-ei29 years . HPV vac < 0.01) . There wAfter AIC-based stepwise backward elimination, the survey-weighted final multiple logistic regression model, assessing the association of HPV vaccination history with HPV-related cancers, was adjusted for age, education, ethnicity, marital status, whether individuals were born in the U.S. or not, income, having smoked at least 100 cigarettes, moderate or vigorous physical activity at work, a history of consuming 4/5 alcohol drinks daily, a history of being overweight, routine access to healthcare services and NHANES cycle . In this891 HPV-vaccinated participants were matched with 891 non-HPV-vaccinated participants using PS matching approach. Covariates between the matched groups were adequately balanced–SMDs were <0.1 for all covariates . In the 25.7% of data a history of consuming 4/5 alcohol drinks every day, 6.6% of data for household income and less than 1% of data for other covariates were missing see the  in the mIn this nationally representative study, the primary analysis showed no association of HPV vaccination with HPV-related cancers. Although the relationship was not statistically significant, participants who were immunized with at least one dose of a HPV vaccine had 42% odds of HPV-related cancers  than those who were not HPV vaccinated. When conducting the propensity score-matched analysis and the analysis on multiple imputed datasets to assess the association between vaccination and HPV-related cancers, we also did not find a statistically significant association. However, a similar trend toward reduction of odds among those who were vaccinated  was observed in the alternative analysis and the sensitivity analysis. The alternative and sensitivity analyses also provided narrower confidence intervals for OR, as they were able to better deal with the small number of HPV-related cancer cases per covariate in the model and potentially increase statistical power by imputing missing data.A similar result was reported in a population-based study from Sweden . UtiliziWe noticed a reduction in HPV-related cancer cases in the last two NHANES cycles, relative to the previous 2011–2012 and 2013–2014 cycles. Similarly, a trend analysis of HPV-associated cancers between 1999 and 2015 using data from cancer registries in the U.S. showed a decline in incidence rates of cervical cancer in all age groups (1.6% decrease per year), vaginal cancer among <40 years old (2.8% decrease per year) and anal cancer among <40-year-old men (2.9% decrease per year) . In AustWe also found a significant increase in HPV vaccination rates from 2011 through 2018. Similarly, other studies have shown an increase in HPV coverage among adolescents ,53 and aAlthough the efficacy and effectiveness of the HPV vaccine against HPV prevalence, HPV-associated anogenital warts and cervical cancer precursors is well supported by the evidence ,56,57,58The study has several strengths. Since we used a nationally representative sample, the study findings are generalizable to the adult non-institutionalized U.S. population. We also conducted secondary and the sensitivity analyses to check the robustness of our study findings. We found similar results across all analyses, suggesting the robustness of the results.There are study limitations that need to be acknowledged. First, in our study, we do not know whether HPV-related cancers were caused by HPV infection, as the outcome data were collected based on self-reporting. Since most cases were cervical cancer (68 out of 72), it is unlikely that other factors might have contributed to their development. Second, differential misclassification bias might have been present. Other anogenital cancers, including vulvar, penile, vaginal, and anal cancers, were not separately reported in the survey, and they might have been classified together under the “Other cancers” group and not included in the outcome. Not including them in the study outcome might have weakened the association by pulling the effect estimate towards the null. Next, since the vaccination status was also based on self-reporting, we cannot exclude the existence of the recall bias, as participants might mistakenly report their HPV vaccination history. However, the recall bias might be limited, since participants were specifically asked whether they received a vaccine against HPV under brand names Cervarix, Gardasil or Gardasil 9 . Since one-dose vaccination might not provide full protection against HPV infections, it might then be inappropriate to compare at least one-dose vaccinated versus unvaccinated. Given the small number of HPV-related cancer cases in HPV vaccinated group, it was numerically challenging for us to estimate the effects of full and partial HPV vaccination in relation to non-HPV vaccination in this study. Due to the small number of events, we were also not able to assess potential effect modifications of covariates  on the relationship. As HPV vaccination before the first sexual onset, at age 11–12 years, is generally recommended, the vaccine might have a lower effectiveness in the older individuals, as they might have already contracted the infection. We were not able to determine whether participants were vaccinated before the first sexual onset or not, since only a few participants responded to questions about sexual behavior. n = 72), most vaccinated participants were between the age of 20–39 years (92.5%). Since HPV-related cancer development may take 10–20 years after first contracting HPV, the majority of participants were not yet at risk of developing cancers, reducing the probability of detecting an association [Another limitation is that non-response bias might be present in the study. More than half of all participants did not know their vaccination status or refused to respond. When we compared characteristics of participants with missing or invalid responses for HPV vaccination status to the complete case data, participants with missing HPV vaccination data had higher rates of HPV-related cancers and were likely from the NHANES 2017–2018 cycle. Additionally, the study timing and the observed rarity of events were the major limitations to finding a statistically significant association. In addition to a small number of HPV-related cancers (ociation ,67,68. TLastly, we also acknowledge that the present study had insufficient statistical power to detect a statistically significant difference between the vaccinated and unvaccinated groups . Future While the analyses found no association of HPV vaccination with HPV-related cancers, the study findings suggest that HPV vaccinated people tend to have lower odds of developing HPV-related cancers than unvaccinated people. Given the importance of determining the impact of the vaccination on HPV-related cancers, there is a need to conduct future research by linking cancer registry data with vaccination records to obtain more robust results. It is understood that the effect of HPV vaccination will be observed in the next coming decades; however, preliminary findings, such as this study, could be used as additional evidence to encourage vaccination among 11- to 15-year-old adolescents and eligible adults, to reduce HPV-related cancer rates and prevent HPV-related cancer cases in the future.


The utilization of the Papanicolaou (Pap) test and the human papillomavirus (HPV) vaccine has significantly decreased rates of cervical cancer and related mortality. Disparities in receiving these preventive screenings are scarcely studied in Muslim females. Our study explores primary care providers’ (PCP) approaches to cervical cancer screening in Muslim females. We created a cross-sectional Qualtrics survey using convenience sampling of PCPs who perform Pap tests in central Ohio. Recruitment emails were disseminated via departmental email listservs. We had 200 analyzable responses and 78% of respondents reported having Muslim patients. Bivariate analysis was used to identify predictors of providers’ approaches. Providers younger than 35 years obtained a sexual history from Muslim females less frequently, family medicine providers were more likely to obtain a sexual history from Muslim females, and gynecologists were more likely to offer the HPV vaccine to Muslim females. Providers who counseled patients about Pap tests (P<0.001) and HPV modes of transmission (P<0.004) were more likely to offer cervical cancer screening for Muslim females. Our findings suggested that providers’ age and specialty may be predictors of proactive cervical cancer screening and prevention in Muslim females and that there is a gap between current guidelines and preventive clinical practices regarding the HPV vaccine and transmission counseling. Since 1Religious factors that impact patients’ healthcare decisions and providers’ perspectives and approaches to these factors are understudied . CurrentA growing number of studies are exploring the difficulties of performing Pap tests on Muslim women . These sEducation about the role of HPV in cervical cancer incidence and the impact of HPV vaccines on primary prevention is another counseling tool for cervical cancer screening encounters . HPV is Muslim women fall at the intersection of many social determinants of health and often have their religious preferences for modesty and provider’s gender concordance overlooked and excluded from shared decision-making. Our study aims to explore providers’ approaches to cervical cancer screening and prevention in Muslim females.2We created a 29-item online self-administered survey. The study met The Ohio State University Institutional Review Board’s guidelines for the protection of human subjects regarding safety and privacy and was documented as an exempt study. We used convenience sampling of clinicians who perform Pap tests including physicians, nurse practitioners, and physician assistants in family medicine (FM), adolescent medicine/pediatrics, obstetrics and gynecology(OB/GYN), and internal medicine (IM). Survey dissemination was managed using Qualtrics, which has a built-in feature that prevents duplicate entries by detecting cookies from the same device. We recruited study participants by utilizing social media platforms  and medical department listservs in central Ohio that provided a summary of the study and instructions for anonymously completing the online survey. Survey distribution occurred between Feb 1st - June 1st, 2021. There is an unknown denominator since the reach of social media and email listservs is not measurable; while our response rate seems comparable to survey-based studies, it was not feasible to calculate it.2.1Our survey items were created de-novo to explore providers’ approaches to cervical cancer screening in Muslim females. The 29 survey items included demographics (Q1-5) and clinical background information (Q6-9) as well as questions regarding provider clinical approach , beliefs (Q18-22), and encountered patient preferences (Q23-25) See .We used Chi-square or Fisher’s exact tests when relevant for subgroup comparisons of survey responses. All hypothesis testing was two-sided and conducted at 5 % type 1 error rate . Survey responses were collected using Qualtrics . Statistical analyses were conducted using SAS version 9.4 .33.1We had 200 responses to analyze by June 1st, 2021. Providers who answered the survey were mostly older than 35 years old (51.5%), female (71%), White (64%), married (60.5%), and had <10 years of clinical experience (60%). Respondents’ specialties were OB/GYN (32.5%), FM (30.5%), IM (17.5%), and Adolescent medicine/Pediatrics (8.5%). Less than a quarter of them are employed in large physician groups (23%) .Table 1P3.2Most clinicians (78%) in our study care for Muslim patients, yet Muslim patients make up less than a quarter of their patient population (65%). Only 1 in 5 providers (20%) reported never identifying the religion of their female patients before preparing them for a Pap test. Three of four providers would personally “always” or “often” obtain a sexual history from female patients before preparing them for a Pap test and are less likely to “always” do so in Muslim female patients  . Almost Most of the providers reported being likely to accommodate gender-concordant care in general (69 %) and a comparable likelihood was seen for religious reasons (68.5 %). Clinicians reported that female patients are more likely to defer pelvic examinations due to fear, disability, religious reasons, preference for OB/GYN, physician gender, and time constraints respectively .Fig. 1WhMost participants (82%) answered “yes” to being familiar with current ACOG and USPSTF cervical cancer screening guidelines and reported following current guidelines either often (20%) or always (61%). Only 1 in 5 providers would “always” offer HPV vaccination to female patients older than 26 years of age with no history of vaginal intercourse or penetration.Most providers reported believing that cervical cancer is mainly caused by HPV exposure (72.5%); however, only 26.5% of providers disagreed with the statement “I believe cervical HPV acquisition can only occur through vaginal intercourse”. Only 13% of providers report always discussing modes of HPV transmission other than vaginal intercourse, with almost 1 in 10 reporting never counseling patients for various modes of HPV transmission.3.3Providers younger than 35 years of age are less likely to follow a belief system that values deferring internal pelvic exams due to either perceptions or concerns about the acceptability of this type of exam within the religious tradition (p < 0.009) or the state or practice of refraining from extramarital or from all sexual intercourse (p < 0.003). Providers younger than 35 years of age also reported less frequency of obtaining a sexual history from Muslim patients before the pelvic examination (p < 0.005). Family medicine providers are more likely to obtain a sexual history from Muslim female patients prior to a Pap test compared to other specialists (p < 0.022) .Table 3BGynecologists are more likely to offer the HPV vaccine to women older than 26 years of age (p < 0.033) and to strongly agree with the statement, “I believe cervical cancer is mainly caused by HPV” compared to other specialists (p < 0.002). This held true for Muslim female patients, but to a lesser extent, where gynecologists are most likely to offer the HPV vaccine to Muslim female patients older than 26 years of age (p < 0.005). Interestingly, providers who are more likely to discuss the indications for a cervical Pap test with female patients who report no history of vaginal penetration or intercourse are more likely to offer the HPV vaccine to female patients in general (p < 0.006) and Muslim female patients (p < 0.001) older than 26 years of age. Providers who discuss modes of transmission of HPV other than vaginal intercourse were more likely to offer HPV vaccine to Muslim females older than 26 years of age (p < 0.004); however, this approach did not statistically predict HPV vaccine offering to older non-Muslim female adults.4Our study showed a high rate of compliance and knowledge of the current cervical cancer screening guidelines, yet providers fail to always obtain sexual histories from patients more than half of the time. Furthermore, providers listed fear as the top reason that patients refuse a pelvic examination, listing religious reasons and physician gender as the third and fifth reasons respectively. It will be of benefit to mirror the providers’ perception to that of patients using the same list of reasons in further research.Of significance, providers’ age, specialty, and the extent of counseling appeared to predict most of their approaches towards cervical cancer screening and prevention in all female patients, particularly Muslims. Provider's specialty is presented in a plethora of studies as a predictor of patient compliance, immunization rate , implemeIn a systematic review, provider-oriented interventions were found to increase cervical cancer screening recommendations by evaluating the provider’s delivery and tailoring screening interventions to the community’s needs rather than a generalizable message . Religio4.1Reflecting on these findings, we believe that building a rapport by personally inquiring about sexual and reproductive health history and transparently counseling patients about the benefits and potential harms of pelvic examination are areas of improvement in clinical practice .Current guidelines have evolved over time to reduce the frequency of Pap tests and pelvic examinations to avoid overdiagnosis and potentially harmful interventions . Also, tEven though 80% of participants reported variably identifying patients’ religion, Muslim female patients consistently received a less attentive approach. One-third of our participants were neutral regarding the statement, “Muslim female patients are more likely to refuse a cervical Pap test due to chastity reasons compared to non-Muslim female patients,” which may manifest in not knowing if this is actually a differentiating reason to defer a pelvic examination for that cohort. Further qualitative research among American Muslim women of all ethnicities is warranted to dissect the role of religion versus culture in defining chastity and provide clinicians with more definitive directions. Most of the studies identified in the literature use “Arab Americans” interchangeably with “American Muslims”  even thoNonetheless, many studies focus on patient-reported barriers to cervical cancer screening without addressing provider-centered factors. Although these barriers exist and create disparities in health outcomes, clinicians are not immune to bias or challenges, especially regarding sexuality and reproductive health . Our finAlso, younger providers obtained a sexual history from Muslim female patients prior to a Pap test less frequently when compared to non-Muslim female patients . This maThere is a plethora of literature regarding the sociocultural barriers Muslim women face in utilizing sexual and reproductive health services, however, the clinical research may be biased toward the said population due to geopolitical affairs. In a content analysis of more than 2000 MEDLINE abstracts about Muslims in clinical literature by Laird et. al, a couple of major themes were noted; deficient and inaccurate representation of Muslim Americans in research and the skewed portrayal of Islamic traditions as unhealthy and discordant with modernized medical services . LeavingFamily medicine providers were most likely to gather sexual history prior to a cervical Pap test, which may be explained by the nature of the longitudinal relationships that family medicine providers have with their patients. This may be of prospective benefit by providing cultural information modules to other primary care specialties and building on this strength in family medicine training. As an example, counseling a group of Iranian women based on a health belief model modified their cervical cancer screening and improved performance .4.2While most of our respondents reported compliance and familiarity with current cervical cancer screening guidelines, only a minority reported recommending the HPV vaccine to their adult female patients older than 26 years of age .We believe that counseling about HPV and the HPV vaccine is another missing recommendation in the current guidelines, as there is a lack of an explicit statement on factoring in virginity and offering HPV vaccines to adult females older than 26 years of age. The role of the HPV vaccine should prove itself a priority in the prevention of cervical cancer over secondary preventive modalities such as cervical Pap tests . Given tI believe cervical HPV acquisition can only occur through vaginal intercourse”. The statement may be endorsed due to the fact that age at first heterosexual encounter and number of sexual partners are the most predictive factors to acquiring cervical HPV (Our findings suggest a knowledge gap that may be compounded by a mismatched interpretation of the sociocultural characteristics of Muslim patients. For instance, many participants reported believing that cervical cancer is mainly caused by HPV exposure; however, only a quarter of them disagreed with the statement “ical HPV , howeverical HPV , finger-ical HPV . In our ical HPV , the abiical HPV . Literatical HPV , especiaical HPV .OB/GYN specialty was significantly linked to a strong agreement with the statement “I believe cervical cancer is mainly caused by HPV” compared to other specialists, another finding that mirrors the literature and indicates another knowledge gap. The gap may be due to the magnitude of exposure to females as a patient cohort, or focused clinical knowledge versus a broad spectrum in primary care settings. In addition, gynecologists were more likely to offer the HPV vaccine to Muslim and non-Muslim females older than 26 years old. This could be due to the availability of the HPV vaccine in gynecology offices, a higher knowledge base of gynecologists, or practice-enforced metrics. Even so, Muslim female patients were offered HPV vaccination at a lower rate by gynecologists when compared with non-Muslim females. Some Muslim patients may be interested in learning if the indicated vaccines are halal, which is not a common knowledge for most providers . InteresOur results indicate that providers rarely counsel patients about modes of HPV transmission, even though most believe cervical cancer is primarily caused by HPV exposure and that vaginal intercourse did not get a full consensus to be the only mode of transmission. This subpar health education and preventive counseling can be remedied by purposeful medical education of both current and future physicians on how to address patients’ needs, thus promoting prevention and healthy changes .Cervical cancer continues to burden women and HPV vaccination rates are well below the Healthy People objectives with regional and ethnic disparities . Further4.3We believe our study offers an equitable and transformative perspective on the accountability of healthcare providers towards all patients and highlights clinicians’ approaches to Muslim females as an underrepresented cohort in clinical research and settings.4.4Our study has the same limitations of cross-sectional design and online-based survey recruitment was challenged by the COVID-19 pandemic in healthcare settings.5Our study intended to explore potential factors that may impact providers’ approach to cervical cancer screening and prevention in Muslim female patients. Our descriptive data brought valuable directions for future research in bridging the gap in caring for Muslim patients and potentially other faith-based cohorts. Furthermore, our analysis suggested that providers’ age and specialty are predictors of proactive counseling with Muslim females, which may require intentional teaching in medical education and residency training. Further exploration of the impact of adherence to clinical guidelines, approaches to counseling underrepresented cohorts, HPV vaccines in Muslim males, and expanding the study to the national sphere to identify regional factors is merited.Sondos Al Sad: Conceptualization, data curation, project administration, resources, supervision, validation, and original and revision writing. Radhika Pandit: Project administration, Data curation, Writing- original draft, review and editing. Nooralhuda Alhashim: Project administration, Data curation, Writing- original draft, review and editing. Mahmoud Abdel-Rasoul: Formal analysis, methodology.The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.


This study aimed to determine the incidence of oncogenic HPV and HPV-related dysplasia in elderly women 5 years after being HPV negative.Cervical cancer prevention for older women can be challenging since there are no specific guidelines for this groupInvited women participated five years earlier in a study where self-sampling for HPV testing was applied, at this time, they were all HPV negative. The women were now, five years later invited to perform self-sampling for HPV testing. Women with a positive result performed a repeat HPV test. Those with a positive repeat HPV test were examined by colposcopy, biopsy and cytology.Of the 804 invited women, 634 (76.9%) agreed to participate in the study and a self-sampling kit was sent to them. Of these, 99.6% (632/634) sent a sample to the HPV laboratory. The participation rate in each age group was 93.3% at age 65, 74.0% at age 70, 80.7% at age 75 and 64.6% at age 80. Overall 18 women  were HPV positive in the first test and 8  in the second test. Sampling for the second test was done on average 5.4 months after the first test. Fifty per cent (4/8) of the women with a positive repeat test had dysplasia in histology.The incidence of HPV in previously HPV-negative elderly women was low. Among women who were HPV positive in a repeat test, there was a high prevalence of low grade dysplasia. Cervical cancer remains a major health problem worldwide with an estimated 530,000 new cases and 273,000 deaths annually , 2. In S). There are two main ways to prevent cervical cancer. Primary prevention with prophylactic (HPV) vaccines has been included in the Swedish vaccination program since 2012. Secondary prevention is based on screening for HPV DNA or RNA and HPV-associated cytological abnormalities [The primary cause of invasive cervical cancer and precancerous cervical lesions is a persistent infection with oncogenic types of human papillomavirus  the participants were 60–75 years old and all women were HPV negative –15 the p. Women wWomen who were repeatedly positive in the second HPV test were offered examination by colposcopy, sampling for histology, and liquid-based cytology (LBC). Three of the authors  performed the colposcopies, cervical biopsies, and curettage for histological diagnosis.Cytotechnicians screened all LBC specimens and those considered abnormal were reviewed by a surgical pathologist. For cervical cytology, the Thin Prep Pap Test was used. The cervical smear was collected with a plastic spatula and a cytobrush. LBC specimens were placed in PreserveCyt solution and processed in the Thin Prep 5000-processor . For the classification of cytology and histology, the Bethesda system was used. Specialists in surgical pathology examined the cervical biopsy samples for histologic diagnosis. All cytology and histology specimens were examined at the Department of Pathology and Cytology, Falun County Hospital, Falun, Sweden.Of the 804 invited women, 634 agreed to participate in the study and received a self-sampling kit. Of the 634 participant women, 99.6% 632/634) sent a sample to the HPV laboratory. The participation rate in each age group was 93.3% at age 65, 74.0% at age 70, 80.7% at age 75 and 64.6% at age 80. Four of the women delivered insufficient samples for the HPV assay and those women received a new self-sampling kit for resampling. Samples from all 632 participants were finally analyzed. Overall 18 women  were HPV positive in the first test and 8  in the second test, collected on average 5.4 months after the first test . Since none of the women had a fully visible transformation zone, sampling was performed by cervical abrasion and random biopsies. Results from LBC revealed 3 benign, 3 ASCUS and one CIN1 while colposcopy with cervical abrasion and random biopsies identified 3 benign and 4 LSIL. No one had signs of vaginal dysplasia at the time of colposcopy. Two women performed a second self-sampling after 1.2 and 1.6 months which not was according to the study protocol. One of them had a positive second HPV test. Both had a non-visible transformation zone at colposcopy and both cytology and histology were benign. No glandular atypia was diagnosed. Women who were HPV negative in the second HPV test, were scheduled for a follow up HPV test one year later after the second one. There was no significant difference in HPV incidence between the different age groups (Table The significance of the detection of an HPV infection among earlier HPV-negative older women is not well studied. One previous study reports on the incidence of HPV and HPV-related dysplasia in women who were HPV negative some years earlier and older than 60 years. It was concluded that older women becoming HPV positive were at high risk of dysplasia . Ageing Studies on the HPV incidence in elderly women are few, but several earlier studies have shown that the HPV prevalence is highest around age 25 and then decreases with age , 29, 30.There are controversies over when to stop screening for cervical cancer, and regarding the significance of a negative exit test . ScreeniIn this study, the incidence of HPV five years after a previous negative HPV test was lower than in the general population of elderly women , 33, butIt is not known whether a woman's age influences her risk for HSIL or cervical cancer in the context of HPV positivity. The significance of a persistent HPV infection with or without LSIL is not well studied in the older age group. It is evident that young women´s data are not necessarily applicable to postmenopausal women and especially not elderly women. Mechanisms involved might include changes in local immune defense, blood perfusion, tissue atrophy, and vaginal microbiota , 26, 34.There are some potential limitations with the study, and they include the participants coming from one single region of Sweden, which might reduce the generalizability of the obtained results. Another weakness is that there was no data on sexual partners during the last 5 years which could have explained some of the cases with HPV positivity. Finally, the histological data were obtained by, in many cases, randomly collected cervical biopsies, which means that there might have been HSIL or cervical cancer in the invisible part of the cervix, in analogy with what has been seen in the study by Aarnio et al. . In thesThe incidence of HPV positivity in previously HPV-negative elderly women was low but low grade dysplasia was common in those with repeat positive tests. Additional research is needed to determine whether elderly women with one negative HPV test are sufficiently protected against cervical cancer.


Type-specific multiplex genotyping assay was conducted at the Centre for Cancer Epidemiology, Tata Memorial Centre, to determine the prevalence of HPV subtypes. The HPV prevalence was observed to be 28.43%, 41.67%, 38.89% and 15.79% in the oral cavity, oropharynx, hypopharynx and larynx tumour tissues, respectively. The HPV 16 genotype was most common in all HNC tumour tissues (30.29%), followed by HPV 58 (0.57%).Although a subset of head and neck cancers (HNC) has been associated worldwide with mucosal high-risk human papillomaviruses (HPV), information on the prevalence of HPV-positive HNC in India is limited. In this study, we examined the prevalence of 21 subtypes of HPV in sub-sites of HNC ( The age-standardised incidence rate of HNC attributed to human papillomaviruses (HPV) infection was 0.5–0.75 per 100,000 and >1.25 in India and Europe and US, respectively in 2012 [et al . The aimThe study was conducted at the Centre for Cancer Epidemiology, Mumbai, India. The HNC subtypes included in the study were OC , OPC , HPC (C12: Pyriform sinus and C13: Hypopharynx) and LC (C32) in the visiting outpatient department of Tata Memorial Hospital. Cases were recruited in the study from 2014 to 2017 only when they were histologically reported as an invasive tumour of the OC, OPC, HPC and LC. Primary cases aged 18–89 with the date of diagnosis not more than 6 months from date of interview were enrolled in the study by trained social investigators. Information of lifestyle habits such as tobacco smoking, chewing and alcohol drinking was collected on a standardised questionnaire.Fresh head and neck tumour tissue biopsy or surgically resected specimens were collected in tissue stabilisation agent RNAlater®. The tissues were stored overnight at 4°C and processed the next day for DNA extraction by using Qiagen® DNAeasy Blood and Tissue kit as per the manufacturer’s instructions. After assessing the quantity and quality of the DNA products, they were then subjected to primer-specific multiplex amplification using Qiagen® multiplex PCR kit. Two primers for the amplification of β-globin were added to provide a positive control for the quality of the template DNA. The development of primers and its sequences have been described elsewhere [After PCR amplification, the samples were analysed by E7-MPG using Luminex technology  as described elsewhere . The HPVIn this prevalence study, we examined the presence of 21 genotypes of HPV in HNC from fresh frozen tumour tissue. Fresh tumour tissues are relatively better biological specimens than serum or plasma to analyse current HPV infection. In our study, we used a type-specific multiplex HPV genotyping (E7-MPG) assay, which combines multiplex PCR and bead-based Luminex technology  . A compaet al [INK4a in retrospectively collected paraffin-embedded tumour tissue specimens. They found HPV DNA positivity of 13.7% in the overall HNCs; HPV16 positivity was 72% in all DNA positive tumours. However, the study concluded that p16INK4a is not a good surrogate marker of HPV transformation in Indian HNC cases which is in contrast to European studies. The differences in the prevalence in our study might be due to Tata Memorial Hospital being a referral centre which receives a heterogeneous pool of patients from all geographical regions of India.A recent study by Gheit et al  conducteIn this study, of all HPV HNC positives (76.8%) we found independently positive for HPV16 DNA. The presence of HPV16 DNA, although necessary, does not establish causality as it might be due to transient infections. Our study also found multiple co-infections of HPV16/HPV58 and HPV16/HPV58/HPV82, which have never been reported in the Indian population . HoweverA comparison of the prevalence studies on HPV in India in development of the HNC tumour is difficult, because of different methods used in HPV detection, type of specimen used and geographical location of the study. Indian studies have reported varying HPV prevalence; these differences may be due to different detecting methodologies or demographics –13. Our By performing type-specific multiplex PCR HPV genotyping assay on 175 fresh frozen tumour tissue samples, we found HPV16 to be the most prevalent genotype in our study. Out of all the HNC subtypes examined, OPC (41.67%) had the highest prevalence of HPV, followed by HPC, OC and LC. A large collaborative study with uniform standardised methodology is required to understand the role of HPV in different subtypes of HNC in the Indian population.Where authors are identified as personnel of the International Agency for Research on Cancer/World Health Organisation, the authors alone are responsible for the views expressed in this article and they do not necessarily represent the decisions, policy or views of the International Agency for Research on Cancer/World Health Organisation.The study was funded by Indian Council of Medical Research grant number ICMR/EU/13/2012/NCD-III.Informed consent was taken from all participants to participate in the study.Informed consent was taken from all participants to disseminate the results of the study.Informed consent was taken from all study participants before the interview and ethical clearance was obtained from the Tata Memorial Hospital Institutional Review Board.Data will be made available on reasonable request.


Cervical cancer is caused by HPV and is nearly completely preventable because of the vaccination and screening available. The present review aims to map the initiatives conducted to implement or evaluate the implementation of HPV testing in Latin American countries. We performed a review search on PubMed in the English language and on grey literature in the Spanish language. We found information concerning HPV testing as primary screening in eight countries. We learned that HPV implementation is not only feasible but a very promising tool for reducing cervical cancer morbidity and mortality. The cost for saving lives and reducing suffering due to morbidity must be pragmatically evaluated by the Latin American governments and improving outcomes must become a mandatory priority for those that are responsible for addressing an organized system of screening.Cervical cancer is caused by HPV. Although it is the fourth most common type of cancer diagnosed and the fourth cause of cancer death, cervical cancer is nearly completely preventable because of the vaccination and screening available. The present review aims to map the initiatives conducted to implement or evaluate the implementation of HPV testing in Latin American countries. We performed the review by searching on PubMed in the English language and on grey literature, as most of the information about the guidelines used was found in governmental websites in the Spanish language. We only found information in eight countries concerning HPV testing as primary screening. Only Mexico has established HPV-based screening in all territories. There are three countries with regional implementation. Two countries with pilot studies indicated results that supported implementation. Finally, there are another two countries with a national recommendation. We have learned that HPV implementation is feasible and a very promising tool for reducing cervical cancer morbidity and mortality. The costs associated with saving lives and reducing suffering due to morbidity of a preventable disease must be pragmatically evaluated by the Latin America governments, and improving outcomes must be a mandatory priority for those that are responsible for addressing an organized system of cervical cancer screening. Cervical cancer (CC) is caused by the persistent infection of oncogenic types of human papillomavirus (HPV), which represents the most common sexually transmitted infection in the world . HPV canSince CC is caused by a virus, it is considered nearly completely preventable . HoweverCurrently, there are two modalities of CC prevention: primary prevention with HPV vaccines and secondary prevention with screening . There aThe present review aims to map the initiatives conducted to introduce or evaluate the implementation of HPV testing in LMICs, specifically in Latin American countries, describing the current status of HPV testing in these localities. We performed the review by searching on PubMed in the English language and also by searching the grey literature, as most of the information about the guidelines used was found on governmental websites in the Spanish language.In May 2018, the WHO called for a global scale-up of CC control that would lead to the eventual elimination of CC. For this, the aim targets were 90% vaccination among girls up to 15 years, 70% of the population aged 35–45 years screened for HPV, and treatment of 90% of precursor and invasive lesions .The VIA method is done by the application of 3–5% acetic acid directly to the cervix, and then a visual inspection is performed to identify color modifications, since dysplastic cells dehydrate turning white (acetowhite areas). VIA is more used in LMICs due to the low cost and, if performed properly, can reduce the mortality rate and the incidence of CC. However, this method has a significant number of false-positives and low accuracy in the results with a sensitivity of 84% and specificity of 82% ,16.The Doyen method for CC screening, the Pap test (cytology), still represents the gold standard in CC screening for many countries, allegedly due to the low cost and acceptable performance reproducibility, despite its low sensitivity. It consists of a morphological analysis of cervix cells, enabling the identification of dysplastic cells and the grade of this alteration. However, because of the impossibility of implementing Pap tests on a high standard basis for several regions of the globe, new methodologies have been gradually replacing the cytology .HPV testing has been proposed as an alternative screening test due to the higher reproducibility and higher sensitivity. Recent studies have demonstrated that HPV-based screening provides greater protection against invasive CC compared with cytology, and due to its high negative predictive ability, there is the possibility to extend the screening intervals to 5 years ,21,22,23The American Cancer Society (ACS) recommends HPV testing every 5 years as the first option to screening; another possibility is cotesting (HPV testing in combination with cytology) every 5 years or, if no HPV testing is available, cytology alone every 3 years . The US There are different strategies for HPV-based screening. Some authors have advocated that the more efficient way is using HPV as primary screening, in which the sample is preserved in a liquid medium that can be used for cytology preparation, with the cytology reserved only for women with HPV positive results (known as a reflex-test). Other authors, however, advocate that is preferable to use the same liquid-based cytology sample for both HPV testing and cytology simultaneously. In these cases, if the genotyping is available and the woman is positive for HPV 16 and/or 18, she should be directly referred to colposcopy .The FDA has approved five tests for HPV detection in cytological specimens: the Hybrid Capture 2 HPV DNA test by Qiagen , Cervista HPV HR test by Hologic , Cobas 4800 HPV test by Roche , the Aptima HPV assay by Gen-Probe , and the BD Onclarity HPV assay by Becton Dickinson . Only the Cobas 4800 HPV test and BD Onclarity HPV assay were approved for primary screening. These two tests are automated and based on PCR with the difference in the HPV region analyzed: the first focuses on the L1 region and the second on E6/E7 .The Cobas 4800 HPV test can identify 14 hr-HPV types: a pool with 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 66, and 68 and genotyping separately of 16 and 18. The sensibility and specificity to CIN2/3 are 92.8–100%, and 24–86.2%, respectively .The BD Onclarity HPV assay can identify 14 hr-HPV types: 16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 66, and 68 simultaneously; discrete individual identification of 16, 18, and 45. The sensibility and specificity to CIN2/3 are 85.7–100%, 17–98.8%, respectively. Additionally, this test has already been evaluated for use in HPV-vaccinated individuals. The sensitivity was lower (80%) and the specificity was higher (52.1%) in vaccinated women than in unvaccinated ones .CC is a huge health problem in Latin America and the Caribbean (LAC) region. Even with a decrease in the incidence of it in some LAC countries, in general, the incidence and mortality rates remain high, demonstrating that it is necessary to improve the screening programs .The first problem is the coverage of the screening programs and the HPV vaccination. A study demonstrated that only 43.6% of women in LMICs self-reported to have ever been screened for CC, with LAC countries having the highest prevalence  . RegardiThe second one is the lower performance of cervical cytology. In developed countries, the sensitivity is around 50%, while in Latin American countries, sensitivity ranges between 22 and 42% ,22.Thirdly, cultural aspects related to pelvic evaluation such as shame, anxiety, the fear of cancer, and poor health literacy affects the impact of cytology-based screening ,14,42.Considering these issues, since the year 2000, there has been a discussion concerning t HPV testing as primary screening in Latin America  with iniThe first initiative in Mexico was in 2013 when a pilot study was conducted to evaluate the performance and cost-effectiveness of HPV-based screening every five years. The study population was women aged 30–64 years who were tested with hr-HPV genotyping (Cobas 4800 HPV test). Women with a positive result for HPV 16 and/or 18 or abnormal cytology (ASCUS+) were referred to colposcopy . The resThen, from 2017 until 2010, another pilot study using the HPV test (hybrid capture 2) as primary screening and using self-collected samples in women aged 25–75 years was conducted. The adjusted positive predictive value of the hr-HPV test was 2.4%, and the negative predictive value was 99.8%. These results suggest that hr-HPV testing in a middle-income country can improve CIN2+ detection .So, currently in México, CC screening is recommended for women between 25 and 64 years, and there are two different modalities according to age: women between 25–34 years are referred to a Pap smear and women between 35 and 64 years are recommended the HPV test. The tests are offered free in all the National Health System centers .As most of the countries in LAC do, Argentina also recommends the cytology-based screening for women aged 25 and older every three years after two consecutive negative Pap smear tests with a 1-year interval. However, an annual screening is a usual practice. A colposcopy and biopsy are recommended for women with an abnormal cytology (ASCH+) ,49.In 2010, Argentina relaunched The National Program on CC Prevention (NPCCP) intending to introduce the HPV-based screening in the Jujuy province. This province had a high CC mortality rate and so it was chosen for the Jujuy Demonstration Project (JDP) . The JDPThe HPV-based screening occurred with women over 30 years old. In the screening scheme, the HPV test was collected (Hybrid Capture 2) and a Pap smear, together with the HPV test that was performed first; if the woman was HPV positive, the cytological slide was evaluated. Women with abnormal cytology (ASCUS+) were referred to colposcopy/biopsy; women with normal cytology were guided to re-screening at 18 months. If the HPV test was negative, women were guided to do a re-screening after 5 years .The JDP enrolled 79.196 women; 29.631 women underwent cytology-based screening, and 49.565 women were tested for HPV. Among the women tested for HPV, CIN2+ was diagnosed in 1.4% against 0.8% among women who underwent cytology tests. The JDP also observed other benefits with HPV-based screening, such as the higher adherence to age recommendations (79.3% to the HPV test vs. 98.8% to the cytology test) and a decrease in inadequate samples (3.6% for the HPV test vs. 0.2% for the cytology test). Therefore, the study authors concluded that the HPV-based tests could accelerate the reduction of the CC rate . It is iBased on these results, the HPV test screening strategy was definitively implemented in Jujuy and extended to other provinces—Buenos Aires, Neuquén, Catamarca, Tucumán, Misiones, Corrientes, and Chaco—using the same flowchart as the JDP study. The country has 24 provinces, and the strategy offered by the public health system was implemented in 8 (33%) of them. There is the intention for a national implementation over time .In Chile, cytology-based screening is recommended for women aged 25–64 years to be performed every 3 years . In 2013Guías Clínicas AUGE Cáncer Cérvico Uterino), Chile started to recommend the HPV test as screening, if available, for women aged 30–64 years. For negative results, the test must be repeated in 5 years. The HPV 16 and 18 genotyping is also recommended if possible, and with a positive result, the women are referred for colposcopy [In 2015, through the AUGE Clinical Guides Cervical Cancer Uterine (in Spanish lposcopy . In 2019lposcopy .Guía de práctica clínica para la prevención y manejo del cáncer de cuello uterino) in 2017, recommended the HPV test for women aged 30 to 49 years every 5 years if they had negative results. In positive cases, the women are referred to colposcopy or VIA depending on the availability. If the HPV test is not available, the woman is directly referred to VIA. For women between 50 and 64 years old, a Pap smear is recommended every 3 years after two consecutive negative results [The government of Peru through the Clinical Practice Guideline for the Prevention and Management of Cervical Cancer (in Spanish  results . Aiming  results .Diretrizes Brasileiras para o Rastreamento do Câncer do Colo do Útero) recommends cytology-based screening for women aged 25 to 64 years every 3 years after two consecutive negative Pap smear tests [Brazil through the Brazilian Guidelines for the Screening of Cervical Cancer  is not used in screening, but since 2014, it has been used to support the follow-up of cases with low-grade lesions ; if the women are <30 years old, the Pap smear is repeated. If there is a persistent positive result, an hr-HPV test is made; if the women are ≥30 years old, the HPV testing is performed directly. Patients with negative HPV results are recommended to repeat the Pap smear after 12 months .Recently, two initiatives emerged with the intentg to test the HPV-based screening in Brazil under “real-life” conditions ,62. The The second pilot started in 2017 in Indaiatuba City (São Paulo State) and is still in progress. The authors are following the age recommended by INCA (25–64 years old) and aim to reach 80% coverage in this population. The HPV test (Cobas HPV Test) has been performed as primary screening. If the woman presents a negative result, the test is repeated in 5 years. Different than other initiatives, in this study, the HPV genotype is considered. Women with a positive result for HPV 16 and/or 18 are referred to colposcopy. If the results are positive and other hr-HPV and abnormal cytology is attested, the women are also referred to colposcopy; if the cytology is normal, the HPV test is repeated after 1 year. In 2017, the Mayor of Indaiatuba City approved a law replacing standard cytology screening with HPV test screening in all the city Public Health Care Centers . The preAll these results support the premise that considers the implementation of HPV tests in primary screening in the Brazilian public health system to be not only feasible but recommendable, although challenging.Between 2014 and 2017, a pilot study with HPV-based screening was conducted in Uruguay (metropolitan region of Montevideo). A total of 1010 women aged between 30 and 64 years old were enrolled. A unique sample collection was used for the HPV test (hybrid capture 2) and Pap smear. Patients with positive results for the HPV test or the Pap smear (ASC-US+) were referred to colposcopy. The HPV test was more effective as primary screening due to the positivity in 100% of the CIN diagnostic. The authors advocate the necessity to conduct a cost-effectiveness study and increase the population enrolled to verify the feasibility of implementing HPV-based screening .Lineamientos técnicos para la prevención y control del cáncer cérvico uterino y de mama) in 2015 for women between 20 and 29 years and aged more than 60 years every 2 years. The HPV test is recommended for those aged 30–59 years every 5 years. If the results are positive, the women are referred to VIA or colposcopy [A Pap smear is recommended in the Technical Guidelines for the Prevention and Control of Cervical and Breast Cancer  for women aged 25–54 years every 3 years. The HPV-based screening is recommended for women between 35–45 years every 5 years. If the result of a Pap smear or an HPV test is positive, the women are referred to VIA or colposcopy according to availability [A Pap smear is recommended in the Guide for the Prevention, Detection and Treatment of Precursor Lesions of Cervical Uterine Cancer  with regional implementation. Two countries with pilot studies (Brazil and Uruguay) indicate results that support implementation. Finally, another two  were found with the national recommendation but without detailed information found about the real status of implementation. It is also possible to observe that the screening interval for HPV tests (5 years) is the same for all countries. However, the target age varies, with the majority starting at 30 years old, as the European and American guidelines recommend. All this information is summarized in Despite HPV testing showing more effective performance than other screening methods for the reduction of CC mortality and incidence, few countries in Latin America had undergone operational implementation in the field of HPV-based screening programs or, at least, initiated any type of study to evaluate the performance of the HPV test in their communities. We can speculate that this fact demonstrates that the economic, social, and political issues in many of these countries prevent both a well-organized program of continued and robust screening strategy and, concomitantly, give access to the transition from cytology-based screening to more effective methodologies, which could bring advantages such as the increase of the testing interval from 3 to 5 years, enable self-sampling, and improve screening sensitivity. Despite many of these real problems, some countries have succeeded in the implementation of HPV testing, or have conducted studies with good results, and should be seen as an example that improvement in the CC prevention scenario is, although challenging, possible in low-income settings. Considering that CC is a preventable condition and that we have learned that it is possible to improve the screening efficacy using molecular HPV tests even in LMICs, we can do better on three major points: Public Health authorities should be sensitized to consider implementing molecular tests as primary screening; comprehensive initiatives to store complete data should be implemented to guarantee an efficient tracing of women; and, finally, investments in technical education and medical infrastructure should be made to assist women diagnosed with severe lesions. The cost of saving lives and reducing suffering due to the morbidity of a preventable disease must be pragmatically evaluated by Latin America governments and be a mandatory priority for those that are responsible to address the challenge of an organized CC screening system, as many countries have already done on other continents with well-documented success.


Conclusions: WLWHs have a high prevalence of HR-HPV anal infection and anal cytologic abnormalities. HR-HPV cervical infection is the main predictor of HR-HPV anal infection.Background: Women living with human immunodeficiency virus (HIV), WLWHs, are at high risk of developing anal cancer associated with high-risk human papilloma virus infection (HR-HPV). We analyzed the prevalence of anal HR-HPV infection and abnormal anal cytology in a cohort of WLWHs and assessed the risk factors for anal HR-HPV infection. Methods: We present a single-center, observational cross-sectional study. WLWHs who underwent anal cytology and anal human papilloma virus (HPV) testing were selected. High-resolution anoscopy was performed in cases of abnormal anal cytology. All suspicious lesions were biopsied. A univariate and multivariate logistic regression model was used to analyze risk factors for abnormal anal screening. The results are presented as odds ratios (ORs) and 95% confidence intervals (CIs). Results: In total, 400 WLWHs were studied. Of them, 334 met the eligibility criteria and were enrolled in the study. Abnormal anal cytology was detected in 39.5% of patients, and anal HR-HPV in 40.1%, with HPV 16 in 33 (26.6%) of them. Concomitant HR-HPV cervical infection was the only independent risk factor for HR-HPV anal infection (OR 1.67 95% CI,  Anal cancer is an uncommon disease in the general population, with an estimated incidence of 1–2 per 100,000 person-years (py) but increasing in recent years in Western countries . Women lHuman papilloma virus (HPV) infection is associated with cervical and anogenital cancers, as well as skin and mucosal lesions. Twelve genotypes have been identified as high-risk types due to their oncogenic characteristics and association with cancer and precursor lesions, whereas types 6, 11, and others, classified as low-risk types, are associated with benign diseases such as genital warts .Around 90% of anal cancers are attributable to a high-risk human papilloma virus (HR-HPV) infection, with Human HPV 16 being the most frequently detected genotype ,8.As for cervical cancer, anal cancer is preceded by high-grade squamous intraepithelial lesions (HSILs) ,10,11. RThe aim of this study was to analyze the prevalence of anal HR-HPV infection and the prevalence of abnormal anal cytology in a cohort of WLWHs. Additionally, we aimed to assess the risk factors for anal HR-HPV infection.We present a single-center, observational, cross-sectional study performed from January 2011 to June 2022 at the Colposcopy and Cervical Pathology Unit of Hospital Universitario 12 de Octubre, Madrid, Spain. WLWHs who were referred for cervical cancer screening or follow-up for a history of cervical H-SIL and underwent concomitant anal cytology and anal HPV testing were enrolled. Patients were excluded who were under 18 years of age with a previous diagnosis of anal cancer and/or in whom neither anal cytology nor anal HPV testing was performed.Clinic and pathologic data were retrospectively obtained from sourced documentation in the electronic medical records (clinic notes and pathologic reports). The study was approved by our institution’s ethics committee  (N°CEI: 21/710), which waived the necessity for informed consent from the patients due to the retrospective nature of the study. All researchers involved agreed to treat the data confidentially in accordance with the General Data Protection Regulation and the Declaration of Helsinki .Anal and cervical cytology and anal and vaginal HPV tests were performed on all patients at the same visit.All anal cytology specimens were collected using a moistened cotton swab. The swab was inserted blindly 2–4 cm deep into the anal canal and rotated 360° for 60 s to ensure that the entire canal was sampled. All cervical cytology specimens were collected using a broom, inserting the central bristles into the endocervix with the outer bristles in contact with the ectocervix, and rotating the broom five turns in the same direction. The swab and the broom were then each placed in a separate preservative solution  for thin-layer preparation (ThinPrep). Specimens of the anal and cervical cytology were processed on a ThinPrep (Hologic) processor and interpreted by a cytopathologist. The results are reported using Bethesda System terminology ; atypical squamous cells of undetermined significance (ASCUS); atypical squamous cells, cannot rule out high-grade squamous intraepithelial lesion (ASC-H); low-grade squamous intraepithelial lesion (LSIL); and high-grade squamous intraepithelial lesion (HSIL)) .® HPV system . This system detects 49 different genotypes of HPV, including the most prevalent high- and low-risk genotypes [Polymerase chain reaction assays for HPV DNA detection were performed with a Clartenotypes .In patients with abnormal anal cytology, HRA was performed using a standard colposcope . Prior to examination, 5% acetic acid solution was applied into the anal canal. Findings were classified according to standard colposcopy nomenclature . All susBiopsies were formalin-fixed and paraffin-embedded, sectioned into 4 μm slides and stained with hematoxylin–eosin for routine histological study. Biopsies were classified as benign, LSIL , or HSIL  . All cytAll patients were evaluated for their basal characteristics. Additional information collected for this group of women included the time of HIV infection, HIV viral load, CD4 count, or time of antiretroviral therapy at the time of anal cytology. Outcome data were recorded in a common database created on the Research Electronic Data Capture (REDCap) tool hosted at the “imas12” research institute .Categorical variables are expressed as relative and absolute frequencies and quantitative data as the mean  when a normal distribution could be assumed, or as the median and interquartile range when it was not possible. Normality was tested using the Shapiro–Wilk test. Statistical hypothesis tests were performed to assess the associations between stratifying and explanatory variables. For categorical variables, Chi-squared tests were used; if the expected frequency in any of the observations was lower than 5, Fisher’s exact test was used instead. As for numerical variables, when normality was assumed, Student’s t-tests for independent samples were performed. When normality could not be assumed, non-parametric Mann–Whitney U tests were used instead.p-value of less than 0.05 was considered statistically significant. All the statistical analysis was performed with Stata/IC 13.0 for Windows.To study the association between anal HPV infection and other risk-related parameters, univariate logistical regression models were applied. To avoid possible confounding factors, multivariate logistic regression analysis was performed. The results are summarized by odds ratios (ORs) and their corresponding 95% confidence intervals (CIs). For all the analyses, a two-sided In total, 400 WLWHs were studied. Of them, 334 patients met the eligibility criteria and were enrolled in the study . ClinicaAs shown in p < 0.001), higher viral load level (p = 0.037), lower CD4+ level (p = 0.002), shorter antiretroviral treatment time (p = 0.017), and in patients with HR- HPV cervical infection (p < 0.001).p < 0.001), remained an independent risk factor for HR-HPV anal infection. HIV infection time, HIV viral load level, CD4+ level, and time of antiretroviral therapy were not independent risk factors, as shown in Multivariate analysis revealed that HR-HPV cervical infection .The results of this study indicate that WLWHs have a high prevalence of HR-HPV anal infection; however, anal intraepithelial dysplasia is not a common finding among them. HR-HPV anal infection is more frequent in patients with a longer HIV infection, higher viral load level, lower CD4+ level, and shorter antiretroviral treatment time, and in those with HR-HPV cervical infection. Most importantly, HR-HPV cervical infection is the principal risk factor for HR-HPV anal infection  ranging from 0.5% to 10.7% ,29,30. T3. These characteristics could explain our low rate of anal HSIL. Additionally, some authors reported higher rates of H-SIL when performing random biopsies in patients with normal HRA [The mechanisms determining whether HSIL develops in the presence of HR-HPV infection are still incompletely understood. In our study, the prevalence of histological anal HSIL was 0.6% (16.7% of the biopsies performed), lower than what has been reported by other authors ,34,35. G3, HPV cervical infection, and younger age (<36 vs. >45 years) [p < 0.001), consistent with the literature. A high correlation between cervical and anal HPV infection has been reported, even with a higher prevalence of anal HPV infection than cervical HPV infection [Several studies have evaluated cervical HPV natural history and risk factors of acquisition, persistence, and precancer progression in WLWHs . Convers5 years) . Univarinfection . TransmiThe main limitation of this study is its retrospective nature, which could have led to some missed confounding factors. Despite these limitations, our study represents a single-institutional cohort with a strict standardization of conditions for anal screening procedures, which was performed by a team specialized in HPV disorders. Additionally, tissue pathology was reported by a pathologist specialized in gynecological oncology in all cases, ensuring highly accurate reports in the majority of cases. Furthermore, to the best of our knowledge, this is the largest study on anal HR-HPV infection and the prevalence of anal abnormal cytology among WLWHs performed in Spain.Our study showed a high prevalence of HR-HPV anal infection (40.1%) as well as a high prevalence of anal cytologic abnormalities (39.5%) in WLWH. Concomitant HR-HPV cervical infection is an independent risk factor for HR-HPV anal infection. The mechanisms influencing whether HSILs develop in the presence of HR-HPV infection are still incompletely understood; therefore, additional efforts should be made to determine the best screening strategies for this population.