One year later, we asked the veterans to provide a DNA sample for analysis and 41.9% of them returned the DNA samples. Overall, most veterans were not interested in genetic testing neither for PTSD (61.7%) nor for addiction (68.7%). However, bivariate analyses suggested there was an association between having the condition of interest and the likelihood of genetic testing on a 5-point scale . While ordinal regressions confirmed these associations, the models with the best statistical fit were bivariate models of whether the veteran would likely test or not. Using logistic regressions, significant predictors for PTSD testing were receiving recent mental health treatment, history of a concussion, younger age, having PTSD, having alcohol dependence, currently taking opioids for pain, and returning the DNA sample during the follow-up. For addiction testing, significant predictors were history of concussion, younger age, psychotropic medication use, having alcohol dependence, and currently taking opioids for pain. Altogether, 25.9% of veterans reported that they would have liked to have known their genetic results before deployment, 15.6% reported after deployment, and 58.6% reported they did not want to know neither before nor after deployment. As advancements in genetic testing continue to evolve, our study suggests that consumer attitudes toward genetic testing for mental disorders are complex and better understanding of these attitudes and beliefs will be crucial to successfully promote utilization.This study explored attitudes toward hypothetical genetic testing for posttraumatic stress disorder (PTSD) and addiction among veterans. We surveyed a random sample of community-based veterans ( Understanding of the genetic bases of psychiatric disorders continues to improve, despite the complexity and various gene–environment interactions that can influence such behaviors . The potA review of studies on general consumer attitudes surrounding genetic testing for psychiatric disorders identified several areas for future study: specifically, the need to study individuals without psychiatric disorders or not involved in genetics-related research, and the need for larger samples . Only onAttitudes toward genetic testing for psychiatric disorders among military veterans are largely unknown despite the high prevalence of certain psychiatric disorders among veterans and the regular screening of patients at VA facilities for psychiatric disorders, including PTSD and addiction , 9. PrevConsumer attitudes toward genetic testing for psychiatric disorders are mixed , 5, 7. IIn this study, we randomly surveyed a cohort of 700 community-based U.S. military veterans with and without psychiatric disorders regarding their attitudes about hypothetical genetic testing at baseline for PTSD and addiction. All study veterans served at least one warzone deployment and were considered to be at risk for these conditions post deployment . One yean = 700) recruited as part of a broader study of the health effects of military service . Participants were also asked when they would have liked to have known their genetic risks . Measures of trust, discrimination, and concerns about privacy were not explicitly assessed in the current survey. However, we did use open-ended survey questions as a way to capture the concerns of veterans, as is commonly done in behavioral research , 32. We Our open-ended questions were administered and coded in accordance with standard procedures for survey research , 32. OpeApproximately 1 year after the survey, veterans were recontacted and asked to provide a DNA sample using Orogene DNA kits manufactured by Genotek, Inc. . Those who agreed to test where mailed a saliva kit with instructions to complete and return to the study team using a postage-paid return envelope. Altogether, 41.9% (95% CI = 38.2–45.6) of veterans returned their DNA kits to the study team.p-value ≥0.05 for variable elimination in order to identify the best predictor variables associated with the likelihood of proving a DNA sample for testing. Our candidate predictor variables included multiple tours, poor/fair current health, high combat exposure, age, education, race, sex, being employed, having health insurance, having current PTSD, having current depression, using the VA for health care, having a positive current screen for alcohol dependence, using mental health services in past year, a history of concussion, using psychotropic medications in past year, using painkillers in past year, and returning the DNA sample at follow-up. Verbatim responses were manually coded by study staff and grouped categorically. “Don’t know” responses for the testing questions (<1%) were deleted for the purposes of regression analyses. Statistical analyses were conducted using Stata, version 13.1 .Descriptive statistics characterized the study sample. Likelihood of testing was analyzed both as an ordinal scale and collapsed into binary outcome variables  for PTSD and addiction, respectively, based on our statistical results. Since the dichotomous measures demonstrated the best statistical fit , 34, we Most veterans were between 40 and 64 years old (59.3%), male sex (95.9%), white race (93.3%), married (79.6%), had some college or higher education (57%), had health insurance (96.3%), were Vietnam veterans (72%), and a significant number (40.4%) currently used the VA health-care system Table . The majA significant number of veterans were classified as having high combat exposure 21.1%), lifetime PTSD (9.6%), lifetime major depression (18.4%), poor or fair current health (31.6%), and having used prescription opioids in the past 12 months (13.9%). Approximately 20% of veterans were taking psychotropic medications (20.6%), had a recent mental health-related visit (21.9%), or had a history of concussion during their deployment (25.9%). In addition, more than 80% of veterans (82.3%) reported that being in combat was a major traumatic event for them , the ordinal logistic regression results for these analyses fit poorly . Consequently, we collapsed these results into binary “yes/no” measures and used logistic regressions for these analyses.The majority of participants responded that they were “Not Likely at All,” or “Not Very Likely” to pursue genetic testing for PTSD , history of concussion , younger age , current PTSD , current alcohol dependence , use of opioids for pain , and returning the DNA sample at follow-up  were associated with the likelihood of genetic testing for PTSD at baseline. For addiction testing, history of concussion , younger age , currently taking psychotropic medications , current alcohol dependence , and the use of prescription opioid painkillers in the past year  were associated with the likelihood of genetic testing for addiction.In veterans who did endorse interest in genetic testing for PTSD or addiction, the final stepwise logistic regression models found seven significant predictors for the likelihood of PTSD testing and five predictors for addiction testing Table . For PTSnot testing are related to not having the condition or being reported as unnecessary . Concerns about privacy, confidentiality, discrimination, insurance coverage, etc., were not mentioned by the veterans.The results for the open-ended reasons given for both interest in and no interest in genetic testing for PTSD and addiction, respectively, are shown in Table The principal study finding was that the majority of veterans were not interested in hypothetical genetic risk testing for PTSD (62%) or addiction (69%) at baseline. Most veterans 58.6%) reported that they would not want to know their genetic status either before or after deployment. The most frequent reasons for lack of interest were not feeling at risk for these disorders and questioning the utility of genetic testing. Participants did not mention trust, ethical issues, or concern about employment. However, the majority of the veterans surveyed (55.3%) were not employed and were over 40 years old (90.6%). In addition, 96.3% reported currently having insurance coverage. Previously, challenges trusting researchers, privacy, discrimination concerns, and questions as to how genetic information would assist in psychiatric treatment were cited as reasons for testing hesitancy 8.6% repo.Having current PTSD increased the likelihood of interest in genetic testing for PTSD fourfold OR = 4.07). Recent mental health treatment, younger age, a history of concussion, a positive screen for alcohol dependence, a use of opioid pain medicines, and having returned the DNA sample at the follow-up, also was associated with interest in genetic testing for PTSD. Our findings differ from a previous study that found veterans in the VA system with PTSD expressed less favorable attitudes toward genetic testing than those without PTSD (. Recent Genetic testing for psychiatric disorder risk would be most useful if testing occurred before the onset of symptoms, or specifically in veterans, before combat exposure. Testing has the potential to promote the practice of precision medicine  by inforGenetic counseling, including education surrounding the clinical utility of genetic testing and the protections afforded by the Genetic Information Non-discrimination Act , may incTo date, our study is the largest investigation of attitudes toward psychiatric genetic testing and included individuals with and without psychiatric disorders who were not already engaged in genetic testing. The prevalence of psychiatric disorders in our community-based veteran sample resembled the general U.S. population more than many VA-based cohorts , potentiIn summary, the majority of veterans did not express interest in genetic testing for PTSD or addiction, two psychiatric disorders of particular relevance to this population and that are of high interest in the VA system and to the veteran community , 46. As The health system’s Institutional Review Board approved the study protocol, and all participants provided informed consent.JAB, JJB, SH, HK, and TU are responsible for study conception, design, and implementation. JJB assisted with analysis and manuscript writing. HK, ML, and JAB conducted data analysis. ML wrote the first draft of the manuscript. All the authors reviewed and approved the final manuscript.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.


Silurus glanis anglers in the UK were collected using questionnaires from a cross section of mixed cyprinid fisheries to elucidate human dimensions in angling and non-native fisheries management. Respondents were predominantly male (95%), 30–40 years of age with <10 yr angling experience for S. glanis; most had received college rather than university education. The majority (34%) were employed with low-moderate income status (<£30k per annum), which may restrict time and expenditure spent on angling. Highest angling expenditure was on equipment and bait with most from southern England (54%) spending >£500 per annum. The proportion of time spent angling for S. glanis was significantly related to angler motivations; fish size, challenge in catch, tranquil natural surroundings, escape from daily stress and to be alone were considered important drivers of increased time spent angling. Overall, poor awareness of: the risks and adverse ecological impacts associated with introduced S. glanis, non-native fisheries legislation, problems in use of unlimited ground bait and high fish stocking rates in angling lakes were evident, possibly related to inadequate training and information provided by angling organisations to anglers, as many stated that they were insufficiently informed.Information about the socioeconomic drivers of  Globally, recreational angling represents a pastime with a high number of active participants, particularly in developed countries across northwest Europe and North America . In EuroUnderstanding the motivations and drivers of anglers contributing to this effort is important to ensure fishery managers implement measures to maintain or enhance angler satisfaction. It can also assist in the general management of exploited fish stocks  and helpSilurus glanis [S. glanis specimen lakes that can account for increased revenues in these fisheries [th Century [S. glanis is present has increased to over 500 in the last 20 years with high fish stocking rates ~1000 kg ha-1in some syndicate waters [An example of a large-bodied, predatory, trophy fish increasingly used to enhance the performance of lake fisheries in England and Wales is the non-native European catfish s glanis . Its popisheries , 10. Pre Century , the nume waters , 12, whie waters , 9.S. glanis introductions are completed illegally, and some of the lake fisheries are in locations that enable natural dispersal, such as on floodplains, resulting in some individual fish dispersing into rivers during flood events [S. glanis has yet to establish invasive populations in England and Wales [S. glanis is already breeding in some angling lakes, of which some are unlicensed and not properly managed [Many d events , 13, 14.nd Wales  because nd Wales  but is p managed .S. glanis fisheries to avoid their riverine dispersal [S. glanis anglers from a representative selection of their fisheries in England to elucidate human dimensions of non-native species angling and fisheries management [S. glanis and fishing practises; 2) establish whether there were different motivations among respondents and reasons for any variability in importance of drivers; and 3) explore whether there are any economic benefits and variation in specialist S. glanis consumerism among respondents.Should this occur, the risks to native species, despite not being fully quantified , 16 are ispersal , 19, 25.nagement . SpecifiS. glanis fishery expert from the Catfish Conservation Group distributed and collected questionnaires from anglers and associated members by mail and also by social media posts . For potential participants, the study relied on good communication from bailiffs and fishery owners to the author EMAR who attended an S. glanis angling event at one of the fisheries for recruitment, with over 30 participant’s questionnaires collected by the end of the day. Overall, there was a good response rate (90%) from participants fishing at specimen lakes when approached on a one to one basis by EMAR, fishery owners or bailiffs on the day, during random weekend visits. The respondent’s demographics were well representative in average age, marital status, house hold number and home area which matched Office National Statistics (ONS) in the UK and other demographic surveys of recreational anglers [Data were obtained from responses to a questionnaire containing 42 questions broken down into five components: 1) social demography; 2) annual angling expenditure; 3) activity trends; 4) motivation; and 5) attitudes and awareness among anglers from a cross section of mixed cyprinid fisheries and the Catfish Conservation Group in the UK. The survey included six fisheries from southern England; Kent, Sussex, Essex, Hertfordshire and two from further north—Yorkshire and Staffordshire. The survey started on 10 May and ended 18 August 2014. A total of 450 questionnaires were distributed by the first author EMAR and by bailiffs and fishery owners using a chain sampling method  with the co-operation and written consent of bailiffs and fishery owners who agreed to participate in the study and allow questionnaire data to be published. In addition, an  anglers , 27. AllS. glanis angling popularity in these areas, may cause some regional bias.The questionnaire was adapted from peer reviewed literature with similar published angler questionnaires , 27. TheS. glanis and they were asked to select from seven options: 1) < 1 yr; 2) 1–5 yr; 3) 5–10 yr; 4) 10–15 yr; 5) 15–20 yr; 6) 20–25 yr; and 7) > 30yr, respectively.The demographic section of the questionnaire was designed to elicit understanding of gender, age, marital status, number in household, angling experience, education, employment and income status of anglers together with possible regional differences. To clarify causal factors related to angler demographic data, respondents were asked to answer from a list of knowledge options to each question, e.g. gender was categorised into male or female, with age ranked into four age groups: 1) 0–29; 2) 30–49; 3) 50–69; and 4) more than 70. Marital status was divided into: 1) single, 2) married or partner; and 3) widowed. Number in the household was categorised into six groups in sequential order. Regions were divided into: Wales, Scotland, East Anglia, South East England, South West England, Midlands and North England. Respondents were asked to select from four options regarding education status; 1) elementary school; 2) technical college; 3) high education college; and 4) university, while employment status was selected from seven categories; 1) unemployed; 2) employed worker; 3) pupil or student; 4) self employed; 5) apprentice; 6) public servant; and 7) retired. Respondents were asked to select from six possible monthly income status groups: 1) < £1000; 2) £1000–1500; 3) £1500–2000; 4) £2000–2500; 5) £2500–3000; and 6) > £3000. The demographic analysis relating to respondents included questions about angling experience of cyprinids and of The second section of the questionnaire was designed to obtain data about the annual expenditure on angling among respondents, e.g. annual expenses of equipment and bait, travel, fishing license, membership fee or day ticket. Each question was answered by selection from six possible options: 1) < £100; 2) £100–£300; 3) £300–£500; 4) £500–£1000; 5) £1000–£2000; and 6) > £2000. The number of fishing licenses per angler was also included and respondents could select from the option list the number of licences they purchased annually.To determine activity patterns and time spent angling, e.g. hours spent actively angling, respondents could select from six options: 1) < 2 hr; 2) 2–4 hr; 3) 4–8 hr; 4) 8–12 hr; 5) 12–24 hr; and 6) > 24 hr. Respondents were asked whether the average time spent fishing from arrival to departure was: 1) < 4 hr; 2) 4–8 hr; 3) 8–12 hr; 4) 12–24 hr; 5) 1–2 days; 6) 2–3 days; and 7) > 3days. In answering the question about days spent fishing in a year, respondents could choose from seven options: 1) < 10 days; 2) 10–30 days; 3) 30–60 days; 4) 60–180 days; 5) 180–240 days; 6) 240–300 days; and 7) > 300 days.The final section of the questionnaire addressed motivation and awareness among respondents. Questions discerning angler motivation were wide ranging and included: enjoyment of nature, escape, socialising with family or friends, opportunity for adventure and accomplishment, the chance to catch a trophy fish, improve fishing skills and learn new techniques. The challenge and size of catfish were also included as questions in reasons for angling. Respondents selected from a 5-point rating scale with the knowledge options of: 1) not at all important; 2) slightly important; 3) moderately important; 4) very important; and 5) extremely important.S. glanis, e.g. disease transmission, trophic impact, predation, hybridisation, establishment and dispersal into rivers, non-native fish legislation and information available from angling organisations were included. The respondents were asked for their level of knowledge by answering from a 4-point rating scale of: 1) don’t know; 2) superficially; 3) partially; and 4) completely.Questions regarding perception and knowledge of risks about S. glanis angling, fishing licenses, awareness of adverse impacts from stocking rates, bait and necessity and period of closed season were included. In answering these questions, respondents were asked to select from a list of 4-point rating scale: 1) don’t know; 2) sufficient; 3) too low; and 4) too high.Similarly, questions concerning views about costs of 2) was used to ascertain whether these variables  were statistically significant. A bivariate analysis was performed to investigate two-way relationships across variables, i.e. regional differences in annual expenditure on bait and equipment, travel, fishing license, membership, day tickets and income status. Bivariate analysis was used to investigate awareness among respondents about risks of disease transmission, trophic impact, predation, hybridisation, establishment and dispersal issues concerning S. glanis in relation to their knowledge of non-native fisheries legislation and perception of how well informed they were by media and angling organisations. Bivariate analysis was also used to determine respondent’s views of bait permissible in angling and adverse risks of high fish stocking rates in angling lakes relative to individual perception of training and information provided by angling groups and media.Descriptive frequency statistics for all categorical independent variables in the questionnaire were determined and the Chi square test . The binary dependent variable, average time spent in angling activity from arrival to departure at fishery was coded as 0 or 1 .Logistic regression, bivariate analysis and the Chi square test were used to determine the relationships between the binary dependent variable (average time spent pattern (high or low) in angling) and independent motivation variables  = β0+ βiXi.where p = the probability of pattern in time spent in angling; (p/1-p) = odds of time spent pattern in angling; β0 = constant; Xi = vector of independent motivation variables; and βi = parameter estimate for the ith independent motivation variable. The individual effects of categorical independent motivation variables on the binary dependent categorical variable were determined, indicating either greater or lesser average time spent angling [The logistic regression method was calculated using:  angling . All sta2 = 135.54, d.f. = 1, P < 0.001). Most S. glanis anglers were between 30–40 years of age with a higher education college or technical college education  receiving an income >£36K   anglers returned questionnaires with the majority of respondents (70%) from south east England. Social demography among respondents indicated a significantly higher proportion of male anglers  .2 = 47.58, d.f. = 20, P < 0.001). Expenditure on travel, fishing license, membership fee or day tickets annual costs were lower than for angling equipment and bait. Most anglers (50%) in East Anglia spent £100–£300 on travel χ2 = 54.15, d.f. = 20, P < 0.001) whereas 58% of anglers spent about £100–£300 on membership or day tickets fees   considered outgoings to be too high  in East Anglia spent £300-£500, with fewer respondents (23%) spending >£500–£1000 with similar trends observed in the Midlands and north of England (χ = 0.01) . The majtoo high .S. glanis highly important , with the challenge in catching S. glanis an influential factor . The need to escape from daily stress and commune with nature were important motivations (P = 0.01) (The majority of anglers (43%) spent on average between 12 and 24 hr fishing from arrival to departure, fishing 10–30 days per year, within a 10–30 miles (16–48 km) fishery radius . The pro = 0.01) .S. glanis were significantly low, with only partial understanding of impacts and superficial comprehension of non-native fish legislative control measures shown by some anglers (30%) . Such poor awareness was possibly linked to inadequate training and information provided by angling organisations and media, as (21%) stated that they were sufficiently informed  believed that the use of unlimited bait was good practise, whereas few had reservations about the adverse impacts from bait overloading and fish overstocking in lakes . Only few (2%) were adequately informed by angling organisations about the risks from high bait loading .Awareness of potential risks and adverse ecological impacts associated with S. glanis in the UK, with large individual fish imported from mainland Europe and higher frequency in riverine dispersal. To enable the primary ecological risks to be identified and development of more robust measures for non-native species education and management requires understanding of the socio economic factors and levels of ecological understanding among the specialist anglers concerned [In recent years, there has been an increase in specialist angling for oncerned , 31.S. glanis angling (for less than 10 years), aged between 30 and 40 years, and educated to elementary or college level rather than university. The highest proportion earned a moderate income (~ £30K per annum) with limited financial and time resources to spend on angling. Most spent between 10 and 30 days per year angling, living within a 16 to 48-km radius from their preferred fishery. Similar results have been found elsewhere, with anglers specialising in catching large common carp Cyprinus carpio in Germany being mostly male [The majority of respondents who participated in this study were male, recently specialised in tly male , fairly tly male , 33 and tly male . For thetly male , 35.S. glanis. The mean cost of a day ticket for specimen lakes was approximately £13.50, approximately twice the cost for lakes holding only species of the Cyprinidae family, highlighting the financial attractiveness to a fishery manager by the addition of S. glanis. As a general rule, many fisheries were run for members, with most having a fixed number of members to restrict angling pressure and preserve angling quality. For these, the mean annual membership fees were approximately £254, although there was variability in, for example, geographic location, intensity of stocking and angling pressure. As recreational fisheries are an integral aspect of rural tourism [S. glanis charging higher access fees might contribute increased annual revenues to local economies [In the present study, there was significant variation in angling expenditure with the greatest expense spent on bait and angling equipment, yet little geographic difference in costs of annual membership or ‘day tickets’ (i.e. the cost to fish during daylight hours) for accessing specimen lakes holding  tourism , 37, theconomies , 39.S. glanis into specimen lakes provided large sized trophy fish for exploitation, good catch rates for anglers and fish hardy to handling stress. This in turn was likely to have resulted in more repeat visits by successful anglers, thus increasing fishery revenue [S. glanis appeared relatively high in the fisheries surveyed consistent with other studies on S. glanis [Esox lucius, zander Sander lucioperca and bull trout Salvelinus confluentus [S. glanis was however, highly seasonal, with catch rates higher in mid-summer than autumn, probably because the species starts foraging at temperatures above 15°C (i.e. in late spring and summer in the UK) [S. glanis into UK fisheries appears unlikely to result in increased revenues throughout the year, but instead display highly seasonal returns.It was apparent that the addition of  revenue . Indeed,. glanis , 9, 40. fluentus . Special the UK) , 9, 40. Effective landscape management of recreational fisheries appeared essential for anglers, as increased time spent angling was significantly related to tranquillity, natural surroundings and escape from daily stress, as found elsewhere , 12. In S. glanis were also significant factors attracting anglers, as most were ‘trophy’ anglers, thus fishing from a somewhat biased perspective. This becomes more relevant for S. glanis anglers because catching large fish requires a certain level of competence and experience, because older fish are cautious to bait enticements and capture [In the present study, both fish size and challenge in capturing  capture . This mo capture , 35, 44.S. glanis stocked into the fisheries, with only partial understanding of the various ecological threats, such as disease transmission, predation, trophic consequences, alteration of community structure, and declines in native species [The majority of respondents had little knowledge of the risks posed by non-native  species . Similar species , 46.S. glanis dispersal and establishment from a proportion of these lakes into some river catchments is highly probable, irrespective of legislation [S. glanis will continue to be stocked by financially-minded fishery managers into lake fisheries with subsequent ecological consequences [Knowledge of non-native fish legislation and fishery management was mostly superficial amongst respondents and related to lack of information. Consequently it seems that islation . In entiequences , 46. Conequences  to addreequences , 39, 47.S. glanis individuals into UK fisheries, which although contributing some socio-economic benefits, we argue there are trade-offs against an increased risk of accelerating their ecological impact following natural dispersal into adjacent river catchments. Prevailing ignorance was detected among the majority of anglers who displayed poor awareness and limited knowledge of any detrimental ecological impacts posed by non-native S. glanis in angling lakes, non-native fisheries legislation and other unsustainable angling practises, compromised by a lack of information and training available to them from angling organisations. Such a response highlights the need for better dialogue between anglers, angling organisations and fishery management; as present risks related to S. glanis are underestimated and given the outcomes from this study, non-native fisheries management in the UK requires more stringent regulations. It is highly probable that S. glanis will increasingly colonize major river catchments, facilitated by warming air and water temperatures predicted for the UK, with their invasion resulting directly from inadequate regulatory control, poor angler education and disreputable fisheries.The long-term aim should be to reassess the exploitation and release of large S1 Text(XLS)Click here for additional data file.S2 Text(DOC)Click here for additional data file.S1 Fig(DOC)Click here for additional data file.S1 Dataset(SAV)Click here for additional data file.


Human papillomavirus (HPV) vaccination holds great promise for drastically reducing the incidence of HPV-associated cancers of the genital tract, and possibly also certain head and neck cancers. Unfortunately, rates of HPV vaccine utilization among adolescents are low in many countries. Many research studies have identified the fact that HPV is a sexually transmitted infection as a barrier to higher vaccination rates. This is related to providers’ and parents’ reluctance to discuss or consider the burgeoning sexuality of their child. An approach suggested to overcome this barrier is to “desexualize” the vaccine. This entails focusing discussions and public messages on the cancer-preventing properties of the vaccine and ignoring or minimizing information about HPV’s sexual transmissibility. In an article by Velan and Yadgar, the authors argue that this approach does more harm than good. This associated commentary offers a slightly different viewpoint from one who has been “in the trenches” both clinically and from a research standpoint for many years. Vaccines against human papillomavirus (HPV) have been available for over a decade and are highly effective at preventing infection with the strains of HPV most likely to cause cancer. While allowing one’s adolescent to receive a vaccine against cancer would seem an obvious choice for many parents, use of the HPV vaccine is far below optimal in many countries. For example, as of 2016 in the US, while 60% of adolescents age 13–17 have started the vaccine series, only 43% have completed it [Though the reasons parents give for not wanting their adolescent vaccinated are multiple, one concern that has been raised by many is the fact that HPV is a sexually transmitted disease. Some parents and medical providers fear that discussing this vaccine in the context of adolescent sexual activity may either provide the adolescent with an impression that sexual activity at their age is condoned, or may raise conversational topics that parents and/or providers may not be comfortable addressing. In response to this concern, many have advocated focusing HPV vaccine discussions on cancer prevention, and minimizing the sexual aspects of the infection.increase levels of vaccine uptake, while contending that on balance there are more people who would be harmed by such a strategy. Examples include adolescents whose parents tend to be passive about vaccination decisions, whose parents feel discussing sex with their adolescent is important, and adolescents that are homosexual.The recent IJHPR article by Velan and Yadgar et al  takes thAs a practicing pediatrician, and one that has studied HPV vaccine utilization extensively, I have had many conversations with parents and their families about this vaccine – some successful and some not. Given this background, I found the article quite interesting. The authors raise several powerful points about why desexualization could be very harmful. For example, when the public perceives that authorities are withholding information , this can significantly undermine trust, and therefore enthusiasm, about the vaccine. In a time of growing vaccine hesitancy for all vaccines , this coYet, as the authors rightly point out, the balance of harms and benefits to desexualizing HPV vaccination is not clear cut, and in some cases desexualizing the vaccine can be advantageous. For example, among parents whose discomfort about discussing sex in the context of their adolescent is strong, or who strongly feel their adolescent will not be at risk for HPV exposure at any point in their lives (regardless of whether this perception is true or not), de-emphasizing the sexual aspect of HPV infection and focusing instead on cancer prevention can be quite useful. In my practice, I personally have encountered such situations many, many times.Escherichia coli in the intestine. I love this approach – it sends the message that HPV is just a part of normal human experience, and therefore has no bearing on ones’ “behavior.” It tells the public what they need to know about how the infection is transmitted, yet does not overlay any judgement about each individual’s own personal risk for infection. Moreover, it paves the way forward for normalization of other vaccines that are likely to be available at some point in the future against other sexually transmitted infections such as HIV, Chlamydia and herpes. The more work we can do now to make vaccination against infections that are transmitted sexually a socially acceptable and routine practice, the better prepared we will be to accept these vaccines as a society if and when they become available in the future.So where does that leave us? In my mind, the best approach falls squarely in the middle, and reflects what I have found most successful in my own clinical experience. First, we cannot actively hide the fact that HPV is a sexually transmitted infection. I believe that it is critical to emphasize that becoming infected with HPV is the norm, not the exception. With nearly 50% of individuals infected (in the US) with HPV at any given time  Fig. 1)1), and mSo, while I believe it is critical to make clear the nature of HPV transmission, given how ubiquitous HPV infection is, I am a firm believer in also de-emphasizing the sexual aspects of HPV. Not only does this approach represent my own small attempt to normalize HPV infection for my patients, but I also disagree with many of the concerns raised by the authors about why such an approach may be harmful. There was a lack of references to scientific studies to provide evidence for several of their arguments, suggesting their conclusions were largely a matter of opinion. As such, I find it difficult to place these arguments over that of my own experience and that of my pediatric colleagues.already had these discussions with their children by the time they are eligible for HPV vaccination! In these parents’ minds HPV vaccination is an extremely minor, or even irrelevant, part of their overall approach to educating their children about sexual health.One such argument that was posited by the authors is that when HPV vaccination is desexualized, it “aborts” liberal parents’ opportunities to engage in a discussion about sex with their adolescent. This has definitely not been my own experience in practice. Instead, the opposite is often true – these are the parents that have typically all types of sexual contact need to be systematically addressed and provided to all adolescents, and that these conversations should occur irrespective of any conversations about HPV vaccination. It is our duty as parents, teachers and medical practitioners to make sure our children are knowledgeable about all sexually transmitted diseases. Even in highly conservative societies, this information is critical for ensuring that, even if not personally relevant, correct information can be conveyed by adolescents to their peers, and eventually to their own children.Another rationale given in the article for the potential harm in desexualizing HPV vaccine discussions is that it obviates the opportunity to discuss the “dangers of male homosexuality” with adolescent boys (and their parents) that may have these sexual inclinations. Yet, in my mind the two are not linked. First, as the authors point out, most adolescents are not well solidified in their sexual orientation during early adolescence, making it a potentially harmful situation to “label” someone as such when they may still be trying to figure themselves out. Moreover, the entire issue of gender identification and sexual orientation is becoming increasingly complex as more and more individuals express a variety of gender identity and sexual orientation permutations . Insteadshould de-emphasize sex and focus more on cancer prevention. Discussions about how to protect oneself against HPV exposure need to be provided in the broader context of overall sexual health and sexually transmitted disease prevention. Emphasizing the sexual transmissibility of HPV infection during the vaccination discussion gives the wrong message to parents by perpetuating the HPV vaccination is only useful for “at risk” individuals, and undermines the reality that essentially everyone is at risk for HPV at some point in their lives. It is my opinion that thinking of HPV as “normal flora” that happens to be transmitted mostly sexually, instead of a “sexually transmitted infection” is critical to shift the thinking of parents, adolescents and society as a whole. Having providers normalize exposure to this infection as an essentially unavoidable party of everyday life could go a long way in helping us as a society realize the full cancer preventing benefits of this remarkable vaccine.To put it succinctly, I agree it would be highly harmful to purposefully try to obscure the fact that HPV is sexually transmitted. Doing so could have serious negative consequences for the public’s increasing skepticism about vaccination. Yet I believe that parent/provider discussions about vaccination


The number of oropharyngeal lesions caused by HPV (Human papillomavirus) has been increasing worldwide in the past years. In spite of the clinical relevance of HPV infection in the anogenital tract of HIV-positive patients, the relevance of oropharynx HPV infection in these patients is not clear. The aim of the present study was to detect HPV infection, and clinical and cytological changes in the oropharynx of HIV-positive patients.Samples collected from the oropharynx of 100 HIV-positive patients were subjected to hybrid capture (HC), conventional and liquid-based cytology. Clinical data were also collected to investigate the relation with HPV status.High and low-risk types of HPV were present in 8% and 16.7% of the total sample. The mean ± sd (maximum-minimum) of the relative ratio light unit (RLU)/cutoff (CO) was 2.94 ± 2.58 (1.09–7.87) and 1.61 ± 0.65 (1.07–2.8) for high- and low-risk-HPV, respectively. By cytology, dysplasia was not detected, but atypical squamous cells of undetermined significance (ASC-US) were diagnosed in two samples. No clinical change, suggestive of dysplasia/cancer, was detected.Our study was able to detect and characterize HPV infection by hybrid capture, which may represent a good tool for screening and follow-up of HPV in the studied population. The frequency and viral load of HPV were low. Neither clinical nor cytological changes suggestive of dysplasia/neoplasia were observed in oropharynx of HIV-positive patients. HPV is a double-stranded DNA virus that is found in mucosa of the oral cavity, upper gastrointestinal tract and the anogenital tract . NowadayThe acquired immunodeficiency syndrome (AIDS) is a pandemic infection and represents one of the greatest public health concerns. The continuous improvement of antiretroviral therapy (ART) led to a better control and treatment of opportunistic infections with a decreased mortality rate and increased overall survival. Hence, a higher cancer incidence is expected in this population which requires the development of new prevention strategies . VirusesThis observational study was conducted at University Hospital of Brasilia and approved by the Institutional Review Board  in accordance with the Declaration of Helsinki Principles. Written informed consent was obtained from all participants. In addition, the study was registered at the Brazilian Human Health Regulator for Research with the approval number CAAE 07802012.0.0000.5327 . Eligible criteria included (i) age ≥18 years; (ii) HIV infection diagnosis (positive serology confirmed by Western blot test).All patients agreed to participate using a semi-structured questionnaire. Data related to demographic characteristics (age and gender), sexual behavior , lifestyle , healthy status  were collected. In relation to sexually transmitted diseases (STDs), subjects were asked about genital and oral ulcerative or warts lesions which were suggestive of these diseases.Subjects were initially submitted to a clinical oral examination to investigate the presence of pre-malignant lesions and cancer . The samples were collected in triplicates from the oropharynx region . The collection technique involved back-and-forth movements in oropharyngeal mucosa. The smears were immediately fixed in 95% ethanol and stained by the Papanicolaou method. Samples were further assessed by conventional cytology, liquid-based cytology and hybrid capture assays.HPV genotype was assessed by hybrid capture  able to identify 13 high-risk HPV subtypes  and 5 low-risk HPV types . The ratio relative light unit (RLU)/cutoff (CO)>1.0 was considered positive.Conventional and base-liquid  cytology was used to assess the cytopathological changes. The cytological slides were examined by two trained and experienced pathologists without the knowledge of each other‘s diagnosis. In cases of non-concordance, the slides of reexamined to achieve a consensus.Candida sp. was diagnosed when pseudo-hyphae and/or small spores were present. Coccobacilli, characterized by small bacilli and cocci organisms, was considered as both isolated and microcolonies appearance. Finally, Actinomyces sp was diagnosed considering its filamentous morphological aspect.The cytological findings were classified according to the current Bethesda system into the following categories: (i) negative, (ii) atypical squamous cells of undetermined significance (ASC-US), (iii) atypical glandular cells (iv) atypical squamous cells-cannot exclude high-grade intraepithelial lesion (ASC-H) (v) low-grade squamous intraepithelial lesion, (vi) high grade intraepithelial lesion and (vi) squamous cell carcinoma . Candidaχ2 and the Fisher test to analyze the different variables. Regarding missing data, this issue was addressed using completer’s only method. Statistical significance was assigned to p < 0.05.Statistical analysis was performed with Graphpad Prism 4  and SPSS1.3 software . The contingence tables used n = 6), hyperemia (n = 5), leucoplakias (n = 3) and tonsillar hyperplasia (n = 3).The demographic characteristics are listed in n = 100). Therefore, high-risk HPV was investigated in 98 subjects and low-risk HPV in 48 subjects. HPV was detected in 16.3% (16/98) of the samples, with high and low risk HPV present in 8.2% (8/98) and 16.7% (8/48) samples, respectively. In samples with high and low-risk HPV the mean ± sd (maximum-minimum) of the ratio RLU/CO  were respectively, 2.94 ± 2.58 (7.87–1.09) and 1.61 ± 0.65 (1.07–2.8). In two cases, high and low-risk HPV were simultaneously detected in the same sample.The amount of sample retrieved for the hybrid capture test was not enough to proceed with high and low risk HPV analysis in all sample size . The frequency of oropharyngeal HPV infection was 14.3% (3/21) in homosexual men, 11.1% (3/27) in heterosexual men and 20% (4/20) in bisexual men. These results did not show statistically significant differences. HPV infection was higher (p = 0.001) in individuals with more than 1 partner and significantly lower in smokers (p = 0.016). There was no association between oropharyngeal HPV infection and condom use, oral or anal intercourse, presence of oral lesions, CD4+ count cells, infection time and presence of DSTs.Oropharyngeal HPV infection was not found in homosexual women (0/19), but it was present in 30.8% (4/13) of heterosexual women  to analyze HPV infection in oropharynx . There iRegarding to methods of sample collection, many procedures are reported for cell collection such as mouth rinsing, saliva collection, scrape and cytobrush . In our Oral sex and open mouthed-kissing have been associated with oral HPV infection in normal and HIV positive individuals and a protected sexual intercourse is the most important factor to avoid HPV oral infection . NonetheWe detected a negative association between oropharyngeal HPV infection and cigarette smoking. It is known that tobacco consumption increases epithelial thickness . TherefoClinical mucosa lesions were detected in 24% of patients. Oropharyngeal HPV infection was present in five patients with lesions, but no association between presence of oropharynx lesions and oropharynx HPV infection was detected. This can be justified because most of these lesions were represented by hyperemia and not by leuko or erytroplakia.Bethesda System is used for classification of cervical and anal malignant and pre-malignant lesions in cytology. Considering that there is a lack of a classification system for HPV related- and malignant and pre-malignant lesions in oral cytology, Bethesda classification was chosen in the current study to proceed the cytological analysis. Such classification has already been used by some studies to classify oral cytological findings . By convCandida sp infection.At to date, there are no studies investigating the association between intraepithelial lesion/dysplasia and HPV viral load in oropharynx. On cervical and anal samples, high viral loads are associated with a greater chance of malignant progression than low viral loads . Among tn = 100) is relatively small. The samples were collected in triplicates from the oropharynx region to be assessed by conventional cytology, base-liquid cytology and hybrid capture assays. However, the volume of the samples provided for the hybrid capture test were not sufficient for the application of the high- and low-risk HPV kits in all 100 patients. High-risk HPV was investigated in 98 samples and low-risk HPV in 48 samples. It was not possible to compare the results of HPV status in oropharynx between healthy and HIV-positive individuals. A control group age and gender-matched would be feasible. However, several important variables would be very difficult to control, such as number of sexual partners, use of illicit drugs, alcohol intake and etc. Besides, the clinical course of HIV and HPV would certainly have interactions that would not be present in healthy subjects. Interestingly, some of such data in the healthy population have already been described previously (The present study should be considered as a preliminary study and some limitations must be mentioned. First, the number of samples (eviously . In addiThe use of hybrid capture was able to detect and characterize HPV infection; hence, this method may represent a good tool for screening and follow-up of this population. The HPV frequency and load viral were low, and neither clinical nor cytological changes suggestive of dysplasia/neoplasia were observed in oropharynx of HIV-positive subjects. In our study, the absence of lesions could be attributed to the low HPV viral load. Therefore, a careful follow-up of patients with ASC-US and HPV infection is recommended to evaluate possible evolution to dysplasia and/or development of others oral lesions.10.7717/peerj.4407/supp-1Supplemental Information 1Click here for additional data file.10.7717/peerj.4407/supp-2Supplemental Information 2Click here for additional data file.


All women are potentially at risk of developing cervical cancer at some point in their life, yet it is avoidable cause of death among women in Sub- Saharan Africa with a world incidence of 530,000 every year. It is the 4th commonest cancer affecting women worldwide with over 260,000 deaths reported in 2012. Low resource settings account for over 75% of the global cervical cancer burden. Uptake of HPV vaccination is limited in the developing world. WHO recommended that 2 doses of HPV vaccine could be given to young girls, based on studies in developed countries. However in Africa high rates of infections like malaria and worms can affect immune responses to vaccines, therefore three doses may still be necessary. The aim of this study was to identify barriers and facilitators associated with uptake of HPV vaccine.A cross-sectional survey was conducted at Eldoret, Kenya involving 3000 girls aged 9 to 14 years from 40 schools. Parents/guardians gave consent through a questionnaire.Of all 3083 the school girls 93.8% had received childhood vaccines and 63.8% had a second HPV dose, and 39.1% had a third dose. Administration of second dose and HPV knowledge were both strong predictors of completion of the third dose. Distance to the hospital was a statistically significant risk factor for non-completion (P: 0.01).Distance to vaccination centers requires a more innovative vaccine-delivery strategy and education of parents/guardians on cervical screening to increase attainment of the HPV vaccination. All women are potentially at risk of developing cervical cancer at some point in their life, yet it is avoidable cause of death among women in Sub- Saharan Africa with a world incidence of 530,000 every year. It is the 4th commonest cancer affecting women worldwide with over 260,000 deaths reported in 2012. Low resource settings account for over 75% of the global cervical cancer burden [Cervical cancer remains the most common cancer in Eastern and Central Africa with an estimated with estimated age standardized rates (ASRs) of 42.7 and 30.6 respectively compared with 2–5 in Western Europe and Australia. Mortality is highest in Eastern Africa at 27 per 10,000 compared to less than 2 per 100,000 in Western Asia/Europe, Australia and New Zealand [Among the Eastern African countries, Kenya has a high cervical cancer burden which is the leading cause of cancer deaths in women of reproductive age and the 2nd most frequent cancer among women in Kenya. The incidence of cervical cancer cases in Kenya is estimated at close to 2500 with annual deaths close to just over 1500 with an average life lost estimated at 25 years. The incidence is projected to double by the year 2025 if no efforts are put to mitigate the increment. Secondary prevention for women in reproductive age is only 3% compared with 40–70% in high resource countries .HPV vaccination as a primary prevention method is supplemented by screening later in life. This is because vaccines do not protect against all high-risk and potential high-risk HPV types. Vaccines to prevent cervical cancers are now available. The quadrivalent Gardasil 4) vaccine protecting against human papilloma virus (HPV) types 16/18/6/11 and the bivalent (Cervirax) vaccine protecting against infection with HPV-16/18 were both originally used as a three dose schedule. A third vaccine, the nonavalent HPV (Gardasil 9) vaccine protecting against HPV types 16/18/6/11/31/33/45/52/58 has been approved by Food and Drug Administration (FDA) in 2014 in the USA . The cos vaccine World Health Organisation has recommended offering HPV vaccination to girls at ages 9–13 and Kenya has developed a comprehensive strategy to address cervical cancer, which includes rollout of HPV vaccination among girls, with the purpose of vaccinating girls naïve to the targeted types. This roll out of HPV vaccine among girls naïve to the targeted types, is akin to the one which took place in Rwanda, Uganda, Cameroon, Tanzania, Lesotho and South Africa, which have introduced HPV vaccine to prevent cervical cancer through school-based programme , 11.WHO has recommended bivalent or quadrivalent vaccine in the 2-dose schedule with a 6-month interval between doses for females less than 15 years old, including females 15 years or older at the time of the second dose based on available studies, before the females become sexually active. A third dose is recommended at least 6 months after the first dose, if the interval between the two doses is shorter than 5 months and for 15 years old or more who are known to be immunocompromised and/or HIV-infected or are already sexually active. This 2 dose recommendation will lead to cost saving and other logistic problems of delivering the vaccine and compliance .Education and knowledge by health personnel and parents/guardians about cervical cancer, HPV and HPV vaccines is necessary for vaccine uptake and hence enhanced primary prevention of cervical cancer –15.An HPThis study sought to explore barriers and facilitators that undermine or promote adherence to 3 doses HPV vaccine in a malaria and helminthic endemic western Kenya and explore policy implications for HPV vaccine introduction. Watson-Jones et al. in their attitudes and access to HPV vaccination among Maasai pastoralists and slum dwellers study found challenges to an HPV vaccination programme included early age of sex and marriage, lack of parental support, school absenteeism and drop-out, population mobility and distance from services. Despite little prior knowledge of cervical cancer and HPV, and school-based vaccination, communities were interested in receiving HPV vaccination. Adequate social mobilization supplemented by out-reach activities, were considered important facilitating factors to achieve high coverage .HPV vaccines in populations whose immunological system may be challenged by multiple co-infections such as malaria and helminth infections are needed measure long term protection and advice on booster doses. Studies have shown that malaria and helminth infections have an effect on long term vaccine responses and hence more research is needed , 18.In 2007 GAP reached more than 445,000 girls in 21 countries and several have implemented a national vaccination program. The burden of cervical cancer remains a big problem in developing world and the GAP initiative through the vaccine delivery will continue to play a valuable role as countries consider large-scale implementation. The demonstration programs and comprehensive analysis of the vaccine delivery has been published in BMC Public Health in May 2012 , 20.In sub-Saharan Africa, many countries are considering the implementation of HPV vaccination. These countries have a high prevalence of endemic malaria and helminth infections that can act as immunological modulators and impact responses to standard immunizations. These infections can impact immune responses to vaccinations –27.Sub-Saharan Africa except South Africa has high incidences of malaria. In Kenya, malaria remains a major cause of morbidity and mortality with more than 70% of the population at risk of the disease (MOH 2014). More than four million cases of malaria are reported annually in Kenya. A 5.1% mortality ratehas been reported among patients admitted with severe malaria. The malaria burden in Kenya is not homogeneous. Western Kenya, areas around Lake Victoria and on the cost present the highest risk –30.A high HPV immunogenicity regardless of the presence of malaria and helminth infections among young girls and women in Tanzania study was found. There was some evidence of enhanced antibody titres to HPV vaccine genotypes in participants with malaria parasitaemia. Additional research on the impact of parasitic infection on the long-term duration of protection from HPV vaccines is warranted .There is a paucity of information on the association between malaria and/or helminthic disease and cervical disease progression. The way malaria and helminths affect the immune response to HPV vaccine long term protection needs to be investigated. Studies should explore differences between levels of HPV 16/18 antibodies after administration of the vaccine among girls exposed to malaria/and or helminthic infections .Through the GARDASIL Access Program (GAP), the Moi Referral and Teaching Hospital (MTRH) was granted 9600 doses of the quadrivalent vaccine to administer to young girls in Eldoret, Kenya. MTRH is Kenya’s second largest referral hospital with a bed capacity of 550 of which 100 are in reproductive health wards, with a service population of 13 million people. It is located in Eldoret town about 325 km from Nairobi in Western part of Kenya. It is a teaching hospital for both undergraduate and post graduate students from Moi University.Eldoret is a principal city in western Kenya. It also serves as the capital of Uasin Gishu County. Lying south of the Cherangani Hills, the local elevation varies from about 2100–2700 (7000–9000 ft). The population was 289,380 in the 2009 census and it is currently the fastest growing town in Kenya.Eldoret experiences highland malaria transmission if temperatures become warm and rainfall encourages mosquito breeding. Residents of Eldoret do not develop immunity and suffer much more serious illness than their lowland neighbours.Promotion of the program was restricted to a number of randomly selected government primary schools, although other girls from the community were not refused if appeared at the vaccination site. A hospital-based vaccination was chosen to reduce the costs of the program.The vaccines were offered to girls of age 9 to 14 years old, from ten primary schools in Eldoret Municipality. These schools were randomly selected until a total of about 4000 eligible girls was reached, expecting a coverage of around 75% (3000/4000). Permission to roll out the vaccination was given from the County Director of Education who in turn instructed the head teachers of involved schools. A training of trainers (TOT) process was set in motion, with teachers first being trained by health staff and through the provision of leaflets the teachers were asked to instruct students and parents/guardians on HPV vaccination and cervical cancer.Vaccination took place from May 2012 to March 2013. After a signed consent was obtained from the parent/guardian, nurses vaccinated the girls. A vaccination card with a next appointment was given upon the first and second dose. Additionally, caregivers who failed to show up on the schedule day were given a reminder by nurses about the second and third dose. Due to a low response during the first 3 months of the program, other schools in the County, government and private, were also invited to participate from August 2012 onwards through posters in the hospital and radio. In September 2012, the program stopped administering the first dose after reaching 3000 girls with a view to guaranteeing sufficient vaccines for the remaining doses.This was done before administration of the vaccine. The questionnaire consisted of two parts. The first part collected information on sociodemographic characteristics, including religion and age of school girls. The second part consisted of questions regarding the guardian’s knowledge of HPV, Pap smear knowledge and whether the female guardian/spouse had undergone a Pap smear test. The survey used in this study was designed by public health specialists and physicians. Data was collected from 22/04/2012 to 23/04/2014 by data collection team. The survey was pilot-tested by for comprehensibility before study commencement.Interviewers administered questionnaires in English, and verbal interpretation in Swahili based on the participant’s request.Following data checking and cleaning, analysis was undertaken using STATA version 12. Corporation, College Station, TX, USA. In order to assess whether a median or mean should be given for continuous variables, a Shapiro-Wilk test at an alpha level of 5% was performed to assess whether the variable was parametric. We checked to see whether the missing data (< 5%) was missing completely at Random by performing the Little’s MCAR test. Prob> chi-square = 0.5472 so indicating that the data missing is completely at random and is unlikely to have altered our results and multiple imputation is not required.Dates for second dose, third dose, Pap smear undertaken, HPV knowledge was dichotomized into the two categories, yes and no. Google maps were used to calculate distance from School to vaccination center. Distance to health centre in kilometres and age were both used as a continuous variable and the non-parametric Mann Whitney rank sum test was performed as it could not be assumed that the continuous variables were normally distributed. Bivariate logistic regression was used to measure the strength of the association, with the dependent variable being the number of dose. Statistical analyses were performed using ‘svy’command to account for clustering in making variance estimates, with school being the primary sampling unit.p-value is 0.05 and borderline significant it was between 0.06 and 0.1.A statistical test was considered significant if the The median age range of schoolgirls whose caregivers were interviewed was 12 (IQR: 10–13), of which, 2853 (99.2%) was Christian and 22 (0.8%) Muslim. 843 (28.1%) had a male parent, 2154 (71.8%) had a female parent and 3 (0.1%) had both. 786 (27%) of parents/guardian had no knowledge of Pap tests. 307(14.4%) of all female guardians underwent a Pap test; 824 (27.2%) of parents/guardians had knowledge of HPV. Of all the school girls eligible for this study 2808(93.8%) had childhood vaccines and 1933(63.8%) had second HPV dose, and 1182 (39.1%) had a third dose. The mean time elapsed between the second HPV vaccine and the first vaccine was 32.5 days (SD 22.7), the third HPV vaccine and the second vaccine 148 days (SD: 17.5). The median time elapsed between the first HPV vaccine dose and the third HPV vaccine dose was 175 days (IQR: 168–182)  and  respectively. A Mann Whitney test revealed that distance to health facility was a statistically significant barrier (p.0.01).Administration of second dose of HPV and HPV knowledge were both strong predictors of taking the third dose of HPV vaccine . A marginal association was observed between Pap test knowledge of the guardian and third HPV vaccine .A 14% higher odds of administration of all three doses was found for girls who had a male guardian , religion  and female guardian who had a Pap test OR 0.9; p:0.6; CI:0.7–1.2. A Mann Whitney rank sum test did not reveal a significant difference in age medians between those who had the third HPV vaccine and those who did not. (p: 0.1). . This research builds on limited research in Kenya on HPV vaccine acceptability for young girls and sought to explore factors associated with administration of the HPV vaccine, which is to our knowledge the first study to explore bottlenecks and facilitators for receiving 2 or 3 doses of HPV vaccine regimen. We have a vaccine uptake of 64% of two doses compared with other countries with less than 50%. Kenya is considering a national HPV vaccine program through GAVI after a successful pilot in 2015.Our study revealed that only about 40% of school girls who had a first HPV dose got the third dose. Our low full uptake findings echo in Becker-Drep’s study et al.  on HPV vOur very strong statistically significant association observed between administration of the second HPV dose and third HPV dose within the six-month time period that was initially stipulated by the WHO before the 2 dose regimen was introduced in 2014 suggests that the majority of guardians who are favourable to a second dose of HPV vaccine are willing and also understand the necessity of having their daughters receive a third HPV dose.Vermandere et al. qualitative study on implementation of HPV vaccine program in Eldoret in Eldoret by key stakeholders showed that caretakers and teachers poorly understood cervical cancer and linked it with modern lifestyle and nonconforming sexual behavior. And few had ever heard about the vaccination opportunity and felt uncomfortable to discuss cervical cancer. Teachers needed support from health care workers to address questions from parents and there was distrust towards HPV vaccines .Masika et al.  found ouDistance was found to be a significant predictor of HPV vaccine uptake, which suggests that a different vaccine delivery strategy be envisaged. This observation also concurs with Vermandere et al. (2012) observations that acceptability of the HPV vaccine may not translate in higher HPV uptake, lest operational problems are addressed for parents.As expected since the outcomes of interest were facilitators and barriers for HPV protection after 1st dose and not uptake of the first dose, it was anticipated that no significant association would then be found between Christian and Muslim religion. With less than 1% of the study population reporting a religion other Christianity, we expected a slightly higher percentage given that the Muslim population in our study setting is close to 10% further studies should be conducted to find out any relationship between religion and vaccine acceptability and uptake.Intuitively, we would have expected female parents/guardians to be significant predictor of three dose vaccine administration; however our results show that male parent/guardians were significantly associated with three dose regimen administration.Also, whilst we observed a strong association between HPV knowledge and HPV vaccine uptake, unexpectedly, no statistically significant association was detected with undergoing Pap smear test by female parent/guardian, which may be indicative of the scarcity of information delivered to women receiving cytological screening on the necessity of HPV vaccine uptake for cervical cancer prevention.The study’s strength is that is our big sample size and that it is the first study to our knowledge that explores facilitators and barriers for HPV vaccine regimen uptake. However, our limitations include lack of data on potential known confounders, including meteorological conditions and time used to travel to the vaccine center as well as other potential unknown confounders which may not have been identified.WHO guidelines 2014 and the CDC guidelines of 2016 have recommended 2 doses of HPV vaccine to girls less than 15 years old except those that are immunocompromised and HIV infected and 3 doses for those 15 years and older, immunocompromised, HIV infected and this may hamper generalizability of our findings .https://www.k4health.org/toolkits/Kenya-health-national-cervical-cancer-prevention-program-strategicplan-2012-2015. The observations derived from our study suggest that the plan could also promote screening for women so that they subsequently understand the importance of HPV vaccination and the completion of the recommended dose regimen. With research ongoing with respect to one dose HPV, implications on HIV, malaria/helminth infestation should be taken into consideration.Our findings highlighting the low HPV vaccine uptake has a number of policy implications which could be addressed within the future Kenyan National Cervical Cancer Prevention strategic Plan (As distance to the clinic was found in our study to be a strong predictor of HPV vaccine uptake, a school-based vaccination, which has a track record of being more efficient , may be Lastly, our current lack of knowledge of operational bottlenecks in Kenya for HPV vaccination uptake would benefit from qualitative studies to inform future quantitative survey tools. Qualitative studies are needed to illuminate our finding concerning why male guardians appear to be conducive to higher uptake of the HPV vaccine regimen.Findings from this study suggested a need to consider school-based vaccination and more active education of caregivers to increase attainment of HPV vaccination regimen. Promoting screening among women so that they, in turn be targeted by an awareness campaign on the importance of HPV vaccination for cervical cancer prevention.Qualitative methods are urgently needed to illuminate our study’s quantitative findings and to inform future time series of cross-sectional surveys to reflect the trends of knowledge and barriers locally.


High-risk human papillomaviruses (HPV) cause cancer at multiple distinct anatomical locations. Regardless of the tissue of origin, most HPV positive (HPV+) cancers show highly upregulated expression of the p16 product of the cyclin-dependent kinase inhibitor 2A (CDKN2A) gene. Paradoxically, HPV+ tumor cells require continuous expression of this tumor suppressor for survival. Thus, restoration of normal p16 regulation has potential therapeutic value against HPV induced cancers. Normally, p16 transcription is tightly controlled at the epigenetic level via polycomb repressive complex-mediated tri-methylation of histone 3 lysine 27 (H3K27me3). Although a mechanism by which HPV induces p16 has been proposed based on tissue culture models, it has not been extensively validated in human tumors. In this study, we used data from over 800 human cervical and head and neck tumors from The Cancer Genome Atlas (TCGA) to test this model. We determined the impact of HPV status on expression from the CDKN2A locus, the adjacent CDKN2B locus, and transcript levels of key epigenetic regulators of these loci. As expected, HPV+ tumors from both anatomical sites exhibited high levels of p16. Furthermore, HPV+ tumors expressed higher levels of KDM6A, which demethylates H3K27me3. CpG methylation of the CDKN2A locus was also consistently altered in HPV+ tumors. This data validates previous tissue culture studies and identifies remarkable similarities between the effects of HPV on gene expression and DNA methylation in both cervical and oral tumors in large human cohorts. Furthermore, these results support a model whereby HPV-mediated dysregulation of CDKN2A transcription requires KDM6A, a potentially druggable target. Human papillomaviruses (HPV) that infect mucosal tissues are classified as low- or high-risk based on the frequency with which they are associated with cancer. Although both types dysregulate normal cell growth, infection by high-risk HPV is a causative agent for cancers at multiple distinct anatomical subsites , 2. HPV HPV encodes two main oncogenes, E6 and E7 . Both arThe HPV E7 oncoproteins alter the regulation of many host cellular genes and much effort has been devoted to understanding the mechanisms by which this occurs . A subseMechanistic studies of these HPV dependent changes on epigenetic regulators of gene expression have focused on altered p16 expression, which is present at high levels in nearly all HPV induced tumors , 33. IndIn a detailed series of tissue culture based experiments, evidence was obtained to suggest that the HPV-mediated reduction in H3K27me3 and subsequent transcriptional activation of p16 required E7 to induce expression of the H3K27 specific demethylases KDM6A and KDM6B , 39. KnoWhile most of this work was done in tissue culture models, similar changes in expression of H3K27me3 regulators were reported in individual cervical carcinomas –30. An aIn this study, we used data from over 800 human cervical  and headThe CDKN2A and adjacent cyclin-dependent kinase inhibitor 2B (CDKN2B) loci encode three distinct tumor suppressors: p16 INK4A, p14 ARF, and p15 INK4B. This gene cluster also encodes a long non-coding RNA transcribed in the antisense direction that is referred to as CDKN2B-AS or antisense non-coding RNA in the INK4 locus (ANRIL)  and suppressor of zeste 12 (SUZ12) components. Multiple studies have reported EZH2 upregulation in HPV+ cancer cell lines, with similarly higher expression reported in small studies of HPV+ cervical carcinomas –30. MuchTri-methylation of H3K27 by PRC2 is proposed to recruit PRC1 via its B lymphoma Mo-MLV insertion region 1 (BMI1) component to maintain a transcriptionally repressive state . A reducThe KDM6A and KDM6B demethylases convert H3K27me3 to the di-methylated or mono-methylated forms . MultiplHPV-mediated changes in epigenetic regulation of transcription of the CDKN2A and CDKN2B gene would be expected to be reflected in methylation status of CpG dinucleotide sequences in or adjacent to these loci. Indeed, a previous report identified altered methylation at 4 CpG loci in this genomic region that correlated with HPV status , 38. We HPV infection and subsequent expression of the E6 and E7 oncogenes leads to a large-scale reprogramming of gene expression. This is likely further exacerbated in high-risk HPV+ tumor cells, which typically express higher levels of these powerful viral regulatory proteins compared to levels found in the context of normal infections. Consequently, high-risk HPV transformed cells exhibit many changes in gene expression that contribute to the acquisition and maintenance of cancerous phenotypes unique to viral transformation . In partWhile cell culture models have allowed detailed analyses of factors involved in virus mediated activation of p16 gene expression from the CDKN2A locus, far less is known about how similar these effects are to actual HPV+ tumors. In this study, our goal was to determine if the changes in H3K27me3 regulators and their target genes observed in cell culture models of HPV transformation are recapitulated in primary HPV+ tumors from different anatomical locations.Using data from over 800 primary human tumors, we provide evidence that HPV+ tumors from both the head and neck and cervical sites exhibit remarkably similar alterations in expression of the genes encoded by the CDKN2A locus . Although rare HPV+ samples have been identified in the TCGA bladder urothelial carcinoma (BLCA) and colon adenocarcinoma (COAD) cohorts, they were not present in sufficient numbers for any useful comparisons. For all genes except p16 and p14, the gene level Firehose dataset was used. For p16 and p14, the gene isoform level Firehose dataset was used (uc003zpk.2 and uc003zpl.2 respectively) to adequately discriminate between these two different products of the CDKN2A gene. Normalized expression data was extracted into Microsoft Excel and the HPV status was manually curated based on published datasets [http://shiny.chemgrid.org/boxplotr/) and assembled into final form using CorelDRAW. For the box plots, center lines show the medians, box limits indicate the 25th and 75th percentiles as determined by R software and whiskers extend 1.5 times the interquartile range from the 25th and 75th percentiles. Statistical significance was calculated using Graphpad Prism v6.01. p-values were assigned using a one-tailed non-parametric Mann-Whitney U test. Post-hoc power calculations were performed with G*Power software version 3.1.9.2 [Level 3 RSEM normalized Illumina HiSeq RNA expression data for the TCGA head and neck cancer (HNSC) and cervical carcinoma (CESC) cohorts was downloaded from the Broad Genome Data Analysis Centers Firehose server . 14 methylation probes were identified to be present in the CDKN2A and adjacent CDKN2B region: cg00718440, cg02400248, cg03079681, cg04026675, cg07562918, cg08390209, cg10848754, cg12840719, cg13601799, cg13926295, cg14069088, cg14430974, cg19133618, cg19481686. Methylation data for all patient samples for these probes were extracted from the Firehose files and assembled into a table using Microsoft Excel. HPV status was manually curated based on published datasets [Level 3 Infinium HumanMethylation450 BeadChip array data for the TCGA HNSC and CESC cohorts was downloaded from the Broad Genome Data Analysis Centers Firehose server (datasets , 61, 62.i and Betai are the M-value and Beta-value of the ith interrogated CpG site [where MCpG site . The dat


Human papilloma viruses (HPVs) cause a variety of clinical manifestations in children including skin warts, laryngeal papillomas, and condyloma acuminatum. Whereas the mode of transmission is well understood and management of HPV infection is clearly defined by guidelines in adults, less is known about the mode of transmission, natural history of disease, and appropriate management of high-risk anogenital HPV infections in children. The patient is a previously healthy 6-year-old female who presented with multiple vaginal lesions causing pain and discomfort and was diagnosed with HPV 18 positive CIN I. Children infected with high-risk HPV subtypes remain a vulnerable patient population, and there is minimal literature on the natural history of disease and effects of overtreatment. Based on a literature review, conservative management, HPV vaccination, and consideration of the cervical cancer screening guidelines for adolescent females are an appropriate treatment course until more studies are reported on cervical cancer screening in survivors of child sexual abuse. Human papilloma viruses (HPVs) are a family of small double-stranded DNA viruses, of which 30–40 genotypes infect the genital tract. The virus infects epithelial cells through abrasion of the skin or mucosa and can exist as a latent infection . Low-risLittle is known about the natural progression of high-risk HPV infection in children. It has been suggested that young children may be monitored for malignancy in a similar manner to adolescent females , 2. PrevThe patient is a premenarchal, 6-year-old female who presented to the emergency department (ED) with her mother because of mild discomfort with urination and “pimples” causing pain in the vaginal area. The patient was previously healthy and denied increased urinary frequency or urgency, vaginal bleeding, vaginal discharge, malaise, and fever. The patient and her mother denied inappropriate contact or touching. On physical examination, the patient was comfortable, smiling, and playful. The external pelvic examination was notable for multiple raised lesions on the labia minora and erythema of the external genitalia. No vesicles or vaginal discharge were observed. At the ED, a clinical diagnosis of genital warts was made.Social Work and the Department of Child Protection and Permanency were contacted. The patient and her mother were referred to a state-designated child protection center that provides crisis intervention and child abuse assessments. At the state-designated child protection center, a team of trained professionals conducted an evaluation and was able to ascertain a history of abuse from the patient by an adult, male family member living in the household. The center conducted a thorough physical examination and infection screening.Two months after initial presentation and evaluation at the child protection center, the patient's symptoms worsened secondary to an increase in the size of the lesion. The patient was able to urinate but unable to sleep at night secondary to pain and irritation caused by rubbing. On examination, the patient had warts in the vestibule that carpeted the space between the labia minora and fourchette, obliterated the vaginal introitus, and appeared to obscure the urethra.The patient then underwent an exam under anesthesia (EUA) and excision of vaginal lesions, as seen in At the postoperative follow-up visit, the mother and patient reported a smooth recovery with minimal pain. Exam of the surgical site in the supine frog-leg position showed that it was well healed with minimal residual disease. The patient was instructed to follow up with gynecology every 6 months and with pediatric surgery as needed. Given this patient falls outside CDC guidelines for vaccination and her pathology results, we plan to recommend HPV vaccination at the patient's next visit , 4.The detection of a sexually transmitted infection (STI) in a child should raise suspicion for sexual abuse. Genital or anal condyloma acuminatum appearing for the first time in a child older than 5 years is likely to be the result of sexual transmission . A retroWhile little is known about the epidemiology of HPV in children, one study demonstrated that 16% (5/31 girls) of child sex abuse victims are infected with HPV . FactorsHPV infections behave differently in adolescent and young women when compared to older adult women . Two expThe Papanicolaou (Pap) test is a screening tool for cervical cancer and has reduced the mortality rates of cervical cancer in the United States . The BetThese guidelines were based on studies of HPV in young women, which can provide insight regarding the management of this 6-year-old female since the natural progression of HPV in victims of child sexual abuse is not known. Although adolescent and young women have higher rates of HPV infection than older adult women, they are also more likely to clear the infection. One study noted that 65–75% of adolescent and young women were found to test negative for HPV DNA by 30 months. The same study suggested chronic HPV infection might be correlated with oncogenic, high-risk HPV viral types, indicating that high-risk viral types may more effectively evade the immune system . AdditioVictims of child sex abuse are an especially vulnerable population for several reasons. Often, as in this case, the sexual abuse begins prior to the age at which HPV vaccinations are routinely given; the FDA has approved HPV vaccination starting at the age of 9 in females. This patient endured sexual abuse at a young age, placing a longer time period between the time of initial infection with HPV and onset of routine cervical cancer screening at the age of 21 . MoreoveThis case of a 6-year-old female victim of child sexual abuse infected with high-risk HPV highlights a vulnerable patient population where there is minimal understanding of the natural course of HPV infection and appropriate management. Further study is needed to ascertain the optimal management and appropriate time to perform a Pap smear . In this