Since licensing in 2006, there has been poor uptake of the HPV vaccine among the targeted population in the South East Asia Region (SEAR) and Western Pacific Region (WPR). A systematic review was conducted to identify the studies exploring the relationship between factors and intention for HPV vaccination among women in SEAR and WPR countries. Nineteen studies were identified as suitable for qualitative synthesis, and three as suitable for meta-analysis. Most women had a positive intention to have an HPV vaccine (range 57%–85%). Having a positive intention to vaccinate was significantly higher among women not aware of HPV infection  and HPV vaccine . Lower knowledge level and less confidence in safety and efficacy of the vaccine, negatively affected intention to vaccinate. Perceiving the vaccine to be expensive, low perception of contracting HPV infection and cervical cancer, and lack of concrete recommendations from healthcare providers also negatively affected intention to vaccinate. This review suggests the decision-making processes of women in SEAR and WPR is influenced by the cost of vaccination, perceived efficacy and safety of vaccine, provision of information on vaccination, and the awareness about HPV infection and the HPV vaccine. The World Health Organization’s (WHO) South East Asia Region (SEAR) and Western Pacific Region (WPR) have two of the highest burdens of cervical cancer3. In 2012, approximately 94,000 and 43,000 deaths from cervical cancer were recorded in the SEAR and the WPR, respectively1. HPV vaccines offer a promising breakthrough to curb the global burden of cervical cancer. Since 2006, the vaccine has been approved for use in over 100 countries. The United States was the first country to introduce a publicly funded HPV immunisation program4. In the WPR, Australia introduced its funded HPV immunisation schedule in 2007, followed by Malaysia in 2010 and Japan in 20114. Conversely, there are no publicly funded HPV immunisation programs in the SEAR. An estimated 118 million women have been targeted for HPV immunisation worldwide and the number of fully vaccinated females in low- to upper-middle-income countries ranges from 1 million to 13.3 million, indicating a low uptake for HPV vaccination in these areas4. The lower response to HPV vaccination is reported to be due to vaccine hesitancy, which underpins reduced vaccine uptake and is defined as a delay in acceptance or refusal of vaccines despite availability of vaccine services5.Human papillomavirus (HPV) has been recognised as the leading cause of cervical cancer, which in turn is the fourth-most prevalent cancer among women worldwide7. However, none have demonstrated a clear association between influences and intention to vaccinate. Moreover, these systematic reviews have not explored the factors leading to vaccine hesitancy among women from the SEAR and WPR. These reviews also lack any quantitative analysis that associates the factors with intention to vaccinate for HPV7. This gap in the existing literature needs to be addressed, especially for the SEAR and WPR, which are regions in which a large female population of various ethnic, religious and socio-demographic backgrounds reside. The findings from this review will be valuable as the provision of statistical and qualitative data synthesis will further strengthen the association of factors that influence women’s decision-making regarding vaccination against HPV. Hence, this information will be of assistance in devising suitable interventions to improve access and acceptability to HPV vaccination in the SEAR and WPR.In this situation, it is vital to explore how the women in the SEAR and the WPR respond to the HPV vaccine; i.e., their intention to vaccinate. This systematic review is one of the first efforts to identify the factors influencing a woman’s intention to have the HPV vaccine. This review will also gauge the knowledge, beliefs and attitude towards the vaccine among women from the WPR and SEAR, as these are fundamental when making decisions about vaccination. To date, existing systematic reviews have summarised predictors of HPV vaccine intention and decision-making among women from the US, the UK, Australia and North America generally, and among African Americans in the US specificallyDetails of the study selection process are described in Fig. 10, Hong Kong11, Japan13, Korea15, Taiwan17, Singapore18, Malaysia20, India21, Nepal22, Thailand25 and the Philippines26. Respondents were recruited from healthcare settings , random digit dialling11, community clusters26 and the internet13. The included studies all involved female respondents, with a total sample size of 22,533. Respondents consisted of mothers/parents with daughters eligible for HPV vaccination25, adult women26 and a combination13 (mothers and daughters). In most of the included studies, the primary outcomes assessed were factors such as awareness, knowledge and attitudes or health beliefs of respondents on practices and preventive measures of HPV infection25. Intention, acceptability or willingness to have the HPV vaccine were often secondary outcomes. Two studies investigated vaccine intention for the women themselves and their daughters23, seven studies for their daughters only25 and ten studies for getting vaccinating themselves26. Mothers were the decision-makers for daughters who were of adolescent age23. Studies among adult women in the SEAR and WPR demonstrated that they themselves made the decision about being vaccinated26. The influence of others  on a woman’s decision to have the HPV vaccine was not explored in most included studies in this review. Eleven studies reported that more than half of their respondents (Range: 56.5% – 84.6%) had a positive intention of undergoing the vaccination for themselves or their daughters25. In comparison, in seven studies fewer than half of the respondents (Range: 3.2% – 46%) had a positive intention to be vaccinated26. More women expressed an intention to have a vaccine (Range: 60% – 97.8%) if it was offered for free, as reported in four studies25.The characteristics of all included studies are shown in Table 24, with scores ranging from 6 to 7; six studies had average quality23 with a score of 5; and the remaining five studies were of poor quality, with scores ranging from 3 to 426.The quality assessment of all included studies in the review is described in Supplementary Table 23. Only one study, by Juntasopeepun, et al.24, reported that there was no significant association between knowledge level of HPV and cervical cancer and intention to get vaccinated, among young Thai women24.Having awareness of HPV, the HPV vaccine, cervical cancer or genital warts does not necessarily mean good knowledge of these. In addition, the type and number of questionnaire items used to assess the knowledge level of women differed markedly between studies, so it was challenging to combine the results. Overall, five studies reported that women having better knowledge on preventive measures of HPV infection and its complications are more likely to express intention to receive the vaccine26. Women who perceive themselves to be at risk of contracting HPV infection and cervical cancer were more likely to have the vaccine than women who do not. In addition, not many women felt that they are at risk of getting HPV or cervical cancer. Three studies reported, respectively, that only 4% (n = 8) of Indian women, 9.5% (n = 37) of Philippine women and 20% of Malaysian women felt that they were at risk of getting HPV26.Eight studies associated women’s perception of contracting HPV and cervical cancer in the future to intention to vaccinate24. Two studies stated that female university students who perceived cervical cancer as very serious had higher chances of getting vaccinated against HPV compared to those who thought otherwise16. The study by Juntasopeepun, et al.24, among college-aged Thai women did not find a significant association between women’s perception of severity of cervical cancer and intention to vaccinate.Three studies measured the perceptions of respondents to disease severity of HPV infection and cervical cancer25. Only one study by Hsu, et al.16, reported that the HPV vaccine’s adverse effects had no significant association with intention to vaccinate.A total of seven studies associated concerns about side effects of the HPV vaccine with non-receipt of HPV vaccination. Six of these studies found that a female parent or a young women’s concern about the adverse effects of the vaccine negatively affected vaccination intentions13. Mothers who doubted the efficacy of the vaccine were not likely to accept the vaccination for their daughters19.Four studies predicted that women’s confidence in the efficacy of the HPV vaccine would affect the intention to vaccinate. Women’s intention to receive the HPV vaccine increases if they are confident in the efficacy of the vaccine in combating cervical cancer, as demonstrated by two studies24. One study in India stated that only 12% (n = 202) of women would agree to pay for all three doses of HPV vaccine, at a cost of $360 US dollars21. On the contrary, the cost of the vaccine was not a profound barrier among mothers in Shandong, China: only 3.79%  of them thought the vaccine was too expensive10.Five studies associated cost concerns with intention to vaccinate. Of these, three studies reported that the cost of the vaccine was a barrier to vaccination25.Concerns about risky sexual behaviour were only shown among a minority of female Thai and Korean college students when asked for their reasons for non-vaccination against HPV26. Women who received recommendations from a healthcare provider were more likely to undergo HPV vaccination26.Women who received a recommendation from others to opt for vaccination were more likely to accept the vaccine compared to those who did not receive any recommendation. The healthcare provider was cited as the most trusted source of recommendation18. Lack of information was the main reason why Singaporean and Korean university students refused vaccination. Only two studies reported concerns about the source of the vaccine10. Doubts about the sources of the vaccine were the major reason for unwillingness to get vaccinated among Chinese women in both rural and metropolitan areas and a minority of mothers in Shandong, China10.Needing more information on HPV-related aspects was shown to have a profound effect in two studies16. Women who are unaware of HPV have a higher chance 1.34 times greater [1.34 (CI 95% 1.02—1.76)] than those aware of HPV of getting vaccinated ] higher among women unaware of the HPV vaccine compared to women aware of HPV vaccine  to get themselves or their children vaccinated against HPV. Despite this, concerns and barriers were identified when a women hesitates to obtain HPV vaccine.27. Our findings of a lower intention to vaccinate associated with improved awareness are consistent with those of Trim, et al.28, obtained from a systematic review of mostly American and European studies (81.1% of included studies). Although the percentage of parents who have heard about HPV rose over time from 60% (2005) to 93% (2009), the intention to vaccinate declined from 80% (2008) to 41% (2011)28. The reason for this decline was that parents were concerned about the safety of the vaccine and wanted more information28. This further affirms that the decision-making process for the HPV vaccination is multifactorial, and an assessment of what hinders women from taking the HPV vaccine needs to consider all the influential factors29. Thus, it is essential to understand that being aware of HPV vaccination and the decision to be vaccinated against the HPV are two different issues, and ‘being well aware’ does not necessarily indicate that an individual will opt for vaccination for their children. Yang, et al.30 reported that personal beliefs and understanding about vaccination are the main factors that dictate the decision not to vaccinate or to seek exemption from mandatory vaccination among well-educated respondents in California. Perlman, et al.29 identified high levels of acceptability of the HPV vaccine despite low levels of knowledge and mixed levels of awareness of cervical cancer, HPV and the HPV vaccine29. It is hard to judge why lower awareness led to higher acceptability of the HPV vaccine, however, a possibility is that due to lack of knowledge individuals may consider the HPV as a bigger health concern in comparison to those who are well educated or more aware of the HPV and its vaccine. Although the fall in HPV vaccine uptake with awareness may be considered counterintuitive, it affirms the multifactorial nature of the decision-making process and underlines the need for assessment of all influential factors. It may be wise to focus on ‘belief modification’ of the public to improve vaccine uptake by targeting information on the importance and safety of vaccines to specific sections of the community30.Based on the results from our meta-analysis, women unaware of HPV infection and the availability of HPV vaccine are respectively 1.34 and 1.57 times more likely to receive vaccination. It is possible that women in the ‘unaware’ group possessed limited information, for example from media sources or friends and may consider the HPV as a bigger health concern in comparison to those who are more aware of the subject. The mixed views on HPV vaccination makes it difficult for parents and young women to make informed decisionset al.6, and Kessels, et al.7, in high-income countries  associated parental satisfaction with the amount and quality of information with vaccine uptake, whereas vaccine refusal was linked to dissatisfaction with information7.From our study, it was evident that wanting more information on HPV vaccination was a reason for refusal among women in the SEAR and WPR. Reviews by Holman, 25. This resonates with findings from Hopkins, et al.31, and Kessels, et al.7, here parental concerns about vaccine safety and side effects negatively affected vaccine initiation.Safety concerns about the vaccine were also found to be profound. Most included studies revealed that women concerned about the side effects of the vaccine had a more negative intention to undergo vaccination19. This negative belief was also reflected in other countries; for example, the US and in Africa, where increased confidence in the vaccine led to a positive intention to have the HPV vaccine35. Effectiveness of other vaccines such as polio and measles influenced respondents’ receipt of the HPV vaccine, as reported by both Katahoire, et al.36 and Ports, et al.37. In addition, parents from developed countries who had previously had their child vaccinated against meningitis or had a positive belief in the efficacy of the vaccine were more likely to get their child vaccinated against HPV28. Confidence in the efficacy of the HPV vaccine was cited in only four studies in this review. In these studies, women who perceived the vaccine to be effective in combating cervical cancer and HPV infection were more likely to receive the vaccination. This was only discussed in African studies, but the results were very varied making it difficult to come to a conclusion38.Our review revealed that women in the SEAR and WPR had doubts about the efficacy of the HPV vaccine. A lack of confidence in the vaccine’s ability to prevent cervical cancer was associated with a more negative intention to get vaccinated40. To date, the only countries that have introduced the HPV vaccine in their national immunisation schedule since its licensure are Australia, Bhutan, Brunei Darussalam, Japan, Malaysia, Singapore, Micronesia and Palau, which together comprise 21% (8/38) of countries in the two regions43. As both the SEAR and WPR mostly consist of low- and middle-income countries (LMIC), setting up a publicly funded HPV immunisation program can be costly, and access to cervical cancer screening programs and healthcare facilities can be a significant issue44. In a study by Ferrer, et al.39, financial concerns came up in high-income countries (HIC) such as the US, Hong Kong and Sweden39. Women in the US were reluctant to go for an HPV vaccination due to the lack of reimbursement by insurance companies, and women in Hong Kong (one of the countries that does not offer free HPV vaccination) thought the vaccine was too expensive39. The HPV vaccine is available to girls aged 13 to 17 in Sweden on a paying basis, which is a barrier for poor families39. A study by Cunningham, et al.38, in Africa on the intention to get the HPV vaccine also revealed cost concerns as an important barrier. Some participants thought the vaccine should be offered for free, while others indicated willingness to pay, but substantially less than the actual cost38. However, cost was not an evident barrier where the vaccine was offered for free, such as in Australia, where the vaccine was provided free for a limited time, prompting young women to get vaccinated40.The cost of the vaccine was a significant barrier for women in the SEAR and WPR, as the HPV vaccine is not funded in most countries in these regionset al.6, on HIC. In addition, women who perceived themselves at risk of getting HPV infection or cervical cancer were more likely to have the vaccine. In comparison, studies in Africa reported otherwise: most parents and adults perceived the risk of HPV infection of cervical cancer for their daughters as high, ranging from 41% to 78%, but its relationship with intention to vaccinate was mixed38. Women in the SEAR and WPR who saw cervical cancer as a serious disease had higher chances of getting vaccinated. This finding resonated with Trim, et al.28, and Cunningham, et al.35, which were literature reviews of HIC and Africa respectively, and which showed that those who recognized cervical cancer as a disease of higher severity were also more likely to accept the vaccine.In both the SEAR and WPR, women who perceived they are at low risk of contracting HPV cervical cancer were less likely to get vaccinated compared to women who thought otherwise. Many women in both these regions also did not feel they are at risk of acquiring HPV infection and cervical cancer, although the reason for this was not explored in all relevant studies. The minority of women who felt they were at risk was reported in the international literature as well. Low perception of the risk of HPV acquisition and misperceptions of need based on sexual activity was also reported in the review by Holman, 39. Irrespective of geography and delivery setting of the HPV vaccine, cultural sensitivity was profound among women when deciding to allow their daughters to undergo vaccination for cervical cancer. Muslim and Asian mothers in the UK and Australia were concerned that giving permission their daughters to be vaccinated would be seen as a sign of approval for sex before marriage46. Some parents dismissed this viewpoint, such as Alaskan and Australian parents, when allowing their child to be vaccinated against HPV47.Concerns about initiating early or risky sexual behaviour among their daughters did not prominently appear in our review, with only two studies citing this concern. In comparison with other regions, this concern appeared mostly among Asian mothers residing in developed countrieset al.6. However, it was also reported in the same study that parents frequently cited not having a physician’s recommendation as a reason for not getting their child vaccinated. Studies in Africa also stated similar findings: a doctor’s recommendation was positively associated with intention to vaccinate38. There is a need for a more tailored health-promotion program for HPV vaccination. In this, it would be useful that parents and young women understand why HPV vaccination is recommended at a young age, the benefits of taking the HPV vaccine and how it outweighs the risks involved (such as adverse effects), the risk factors involved in acquiring HPV infection, and the efficacy of the HPV vaccine in preventing genital warts and cervical cancer. Abolishing the cultural and religious barriers may be impossible, but pitching the vaccine as a cervical cancer vaccine rather than the HPV vaccine may help improve uptake. In addition, it is recommended that parents and young women be educated on why the HPV vaccine needs to be obtained at a young age rather than later. Although there were uncertainties about the benefits of vaccinating women aged 15 to 45 years48, Gardasil was reported to remain highly effective in preventing HPV-related diseases in females of this age group who were HPV-naïve49 but less effective in those who may have had a previous HPV infection50. Thus, GPs should still consider older women who may benefit from HPV vaccination by taking into account of their previous exposure and the risk of future exposure to HPV. Reducing the cost of the vaccine also needs to be considered; support from donations and government subsidies would be useful to help reduce the cost of getting the HPV vaccine. Access to healthcare facilities among populations in rural settings needs to be investigated, and suitable interventions are needed to ensure the populations there are also educated about the HPV vaccine.Support from family and friends and a physician’s recommendation are also important when women in the SEAR and WPR decide about having the HPV vaccine. Regardless of a country’s income status and cervical cancer mortality rate, women in the SEAR and WPR had the same concerns and barriers as women from other countries regarding intention to have the HPV vaccine. A women receiving support from her parents, encouragement from friends or recommendation from a physician is more likely to have the vaccine. Receiving a physician’s recommendation or discussing the HPV vaccine with a physician was associated with vaccine acceptance and initiation in numerous studies from HIC as reported by Holman, This systematic review provides a comprehensive summary of the concerns and barriers that women in the SEAR and WPR have when making informed decisions on HPV vaccination. It is a good reflection of factors contributing to HPV vaccine hesitancy in populations that are at high risk of developing cervical cancer and HPV infection despite the availability of vaccine services. However, this review is limited by studies that mostly recruited populations from cities or urban areas, so it cannot be generalised to other populations such as rural residents, ethnic minorities or immigrants. Further, this review may not be applicable to all LMICs, as there may be pilot schemes or GAVI projects in which vaccine hesitancy cannot be applied.Intention to vaccinate was generally positive among women from the SEAR and WPR. The main factors that led to a negative intention to receive the HPV vaccine were the cost of vaccination, concerns about efficacy and safety of the vaccine, lack of information on vaccination, and lack of awareness about HPV infection and the HPV vaccine. Future research should involve investigations of the actual uptake and completion of HPV vaccination, and barriers to receiving the HPV vaccine . Health promotion programs for the HPV vaccine should clarify women’s risks of acquiring HPV infection and the benefits of getting vaccinated, while being culturally sensitive.http://www.crd.york.ac.uk/PROSPERO/display_record.asp?ID=CRD4201603574951.A systematic review was performed using Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). The protocol for this systematic review is registered under Centre for Reviews and Dissemination (PROSPERO) and is available from: st December 2016 were considered for inclusion. Six databases, namely Pubmed, EMBASE (Ovid), PsycINFO (Ovid), Cochrane, MEDLINE (EBSCOhost) and CINAHL Plus (EBSCOhost), were systematically searched using search terms and keywords by three independent reviewers . To capture all relevant influential factors involved in women’s decision-making processes for having the HPV vaccine, the following Mesh terms were used in Pubmed, connected with Boolean phrase AND: “papillomavirus infections”, “female”, “papillomavirus vaccines”, “health knowledge, attitudes, practice”. Details of search strategies in the remaining databases are provided in the Supplementary Table All the relevant studies from inception till 31Upon completion of the search across six databases, the following inclusion criteria were used to identify the potential papers for qualitative and qualitative synthesis: (1) A quantitative study that examined the factors influencing women’s decision-making processes in obtaining the HPV vaccine and their intention to obtain the HPV vaccine; (2) The study was conducted in WHO-defined SEAR and WPR; and (3) The study recruited participants eligible for HPV immunisation; i.e., girls aged 9–13 years old and girls aged ≥ 15 years old. Parents who had daughter’s eligible for HPV immunisation were also included.Studies meeting the inclusion criteria were further screened for duplication by three independent reviewers . After reaching a final consensus about the article numbers, the full-text articles of the studies were then screened for the final inclusion. Disagreements were resolved by discussion and consensus between three reviewers . If no agreement could be reached, the remaining two reviewers (TK and PSS) made a decision. The identification and inclusion of articles is depicted in a PRISMA flow diagram Fig. .The data extraction form was developed in an Excel spreadsheet. The form was piloted from two trial reports to ensure suitability for use. A completed extraction form is attached in Supplementary Table The primary outcome of interest for this systematic review was the intention to vaccinate for HPV. Any other relevant information that encompassed awareness and knowledge of HPV-related aspects, factors accepting or rejecting vaccination, sources of information, and attitudes and beliefs, were also considered for further comparison between the studies.52. One author (DS) evaluated the quality of included studies on both study and outcome levels  which reports the quality of studies on a scale of 0 to 1053. Studies with binary data that was not combinable due to marked variation between studies were synthesised narratively.Articles presenting data relevant to the outcomes of interest were further subjected to Meta-analysis using Review Manager (RevMan), version 5.3. A random effects model was applied during analysis because the true effect size varies according to differences in population from study to study. The odds ratio (OR) was computed together with inverse variance and 95% confidence interval (CI) for calculation. We tested for heterogeneity to measure inconsistency of effects across studies. The level of heterogeneity between and within studies was determined as either low (25%), moderate (50%) or high (75%)Supplementary Table S1Supplementary Table S2Supplementary Table S3


Human papillomavirus (HPV) causes tumors primarily Cervical cancer. Recently, inconsistent reports came up in Breast cancer (BC) too. In India, despite treatment 70,218 BC patients die each year. So, we explored the association of HPV, if any, with BC prognosis in Indian pre-therapeutic (PT) and Neo-adjuvant chemotherapy (NACT) patients with subsequent analysis of HPV profile.HPV prevalence was checked and analysis of physical status, copy number, genome variation, promoter methylation and expression (mRNA and protein) of the prevalent subtype was done.High prevalence of HPV was observed in both PT (64.0%) and NACT (71.0%) cases with significant association with younger (20–45 yrs) PT patients. Interestingly, HPV infection was significantly increased from adjacent normal breast , fibro adenomas  to tumors  samples. In both PT and NACT cases, HPV16 was the most prevalent subtype (69.0%) followed by HPV18 and HPV33. Survival analysis illustrated hrHPV infected PT patients had worst prognosis. So, detailed analysis of HPV16 profile was done which showed Europian-G350 as the most frequent HPV16 variant along with high rate of integration. Moreover, low copy number and hyper-methylation of P97 early promoter were concordant with low HPV16 E6 and E7 mRNA and protein expression. Notably, four novel variations  in the LCR region and two (KT020836 and KT020837) in the E6 region were identified for the first time along with two novel E6^E7*I (KU199314) and E6^E7*II (KU199315) fusion transcript variants.Thus, significant association of hrHPV with prognosis of Indian BC patients led to additional investigation of HPV16 profile. Outcomes indicated a plausible role of HPV in Indian BC patients. Human papillomavirus (HPV) is a DNA virus having a 9.2Kb genome. The high-risk (hr) subtypes were frequently associated with different cancers, primarily cervical cancer (CACX) and Head and neck squamous cell carcinoma (HNSCC) . Among tIn recent times, several worldwide reports have associated HPV with Breast cancer (BC) while other investigators have strongly negated it. A current meta-analysis encompassing 21 different studies had also revealed this inconsistency in prevalence of high risk HPV16 (ranging from 3% to 92%), HPV18 (2% to upto 100%) and HPV33 (4% to 70%) . In addiOn the other hand, in India, where 144,937 BC cases were newly diagnosed and 70,218 BC patients die per year in spite of therapy, variable frequencies (from negative to up to 26.5%) of HPV infection in BC have been found . But tilThus, in the present study, attempts have been made to analyze the association of HPV, if any, in BC of Indian patients. At first, we analyzed the prevalence of HPV in 272 pre-therapeutic and 41 NACT BC of Indian patients followed by prevalence of high risk HPV16, 18 and 33. Our study showed high frequency (63.9%-71%) of HPV infection in the both pre-therapeutic and NACT samples with highest prevalence of HPV16. PT patients with hrHPV infection showed worst prognosis as well. So, further analyses were done to decipher the genetic and epigenetic status of HPV16. Finally, integrated genome, P97 promoter methylation, low viral copy number along with reduced expression (mRNA/protein) of its oncoproteins E6/E7 were the attributes of HPV16, frequently encountered in Indian BC patients.®  solution which is separately stored. Among these samples 56.8% (178/313) patients were below the average age of 45.6 years and 43.1% (135/313) were above the average age , Kolkata, India, after appropriate approval of Institutional ethical committee and written consent from individuals. After surgery, some portion of the operated specimen was collected by the surgeons in sterile pots in the operating room. These were then cut into pieces by sterile surgical blades. One part of the tissues were stored in 10% formalin for immunohistochemistry (IHC) analysis and the remaining part stored at -80°C in isolated rack until further use. In addition, standardized precautions were taken to avoid contamination during tissue preparation. For RNA analysis some of the pre-therapeutic samples (N = 10) were kept in RNAlaterrage age . As samprage age .The contaminant normal cells in the breast lesions were removed by micro-dissection procedure  to enric32P-labeled HPV16 and HPV18 type-specific probes (TIF)Click here for additional data file.S2 Fig(a) HPV16 (b) HPV18 detection agorose gel in NACT and pre-therapeutic sample.Corresponding autoradiograph of (TIF)Click here for additional data file.S3 Fig(a) pre-therapeutuc and (b) NACT patients.No statistically significant association was observed in survival probability of HPV infected (TIF)Click here for additional data file.S4 Fig(a) E6*II/E7 transcript showing junction of the splicing site (nt225/526) (b) E6^E7 transcript showing junction of the splicing site (nt226/742) (c) E6^E7*I transcript showing junction of the splicing site (nt174/718) (d) E6^E7 *II transcript showing junction of the splicing site (nt221/850). Novel splice form was shown in bold.Representative sequence chromatogram of (TIF)Click here for additional data file.


After the publication of this Meeting Abstract  it was n


For the majority of serving members, life in the military has a positive effect on wellbeing. However, the type, intensity and duration of service, along with the transition from fulltime military to civilian life, may have a negative effect on veterans’ wellbeing. Such negative consequences, alongside the growing veteran population, indicate the need for greater exploration of veterans’ physical, mental and social wellbeing.The current paper reports on the findings of a rapid review of the literature on the health and wellbeing needs of veterans, commissioned by the Australian Department of Veterans’ Affairs to inform future programs and services. The databases Embase, Medline, Cinahl, PubMed, Web of Science and Cochrane Database were searched for systematic reviews reporting on veterans’ physical, mental and social wellbeing published in English in peer-reviewed journals.A total of 21 systematic reviews were included. The reviews reported on a range of mental, physical and social health problems affecting veterans. While there was limited information on prevalence rates of physical, mental and social health problems in veterans compared to civilian populations, the reviews demonstrated the interconnection between these domains and the effect of demographic and military service factors.A key finding of the review is the interconnection of the mental, physical, and social health of veterans, highlighting the importance that an integrated approach to veterans’ wellbeing is adopted. It is suggested that understanding key factors, such as demographic factors and factors relating to military service, can support improved service provision for veterans.The online version of this article (10.1186/s12888-017-1547-0) contains supplementary material, which is available to authorized users. Veterans (defined here as ex-members of the armed forces) are a growing population in Australia, the United Kingdom (UK) and other countries, particularly since the return of veterans from the Iraq and Afghanistan conflicts –3. In thVeterans have been observed to have a lower mortality risk relative to the general population. This has been referred to as the ‘healthy soldier effect’, resulting from the high physical health standards of entry into the armed forces . HoweverThe healthcare needs of veterans are complex , 11, relWithin the structured environment of the Australian Defence Force, as in most countries, fulltime members enjoy unrestricted access to health care services that cater to the general wellbeing needs of individuals. Following transition from the defence force, veterans may need to adjust to a new, and less structured, environment, which may not provide them with the same support provided while serving. In 2015 the Australian Department of Veterans’ Affairs (DVA) commissioned a rapid review of the literature on the health and wellbeing needs of veterans in order to inform future programs and services. The World Health Organization  AND Humans[Mesh]) AND systematic AND (Review[ptyp] AND Humans[Mesh])Web of Science: veteran AND ‘systematic review’Cochrane Systematic Reviews: veteranThe following databases and search terms were used:The term ‘veteran’ was used as the primary population search term because it is the Medical Subject Headings (MeSH) term relating to former members of the armed services. No synonyms (such as ‘ex-forces’) were used because in a test search these were found to yield high numbers of unrelated results, which is prohibitive in a rapid review. Given that the review was focussed on all aspects of veterans’ wellbeing, the decision was made to initially search for all systematic reviews relating to veterans. Had this yielded a prohibitively large number of results then the search would have been further delimited using date limits and, if necessary, adding search terms relating to physical, mental and social wellbeing. The initial search was conducted in July 2015 and updated in September–October 2016.Inclusion criteria for the review were: systematic review of the literature; includes military veterans who are no longer in active service; explores the physical, mental and/or social health of veterans; published in English; peer reviewed. Exclusion criteria were: non-systematic review; systematic review protocol; does not include veterans; focussed on a health care intervention; published in a language other than English.The search yielded 386 abstracts, reduced to 320 after removal of duplicates. An abstract screening form was developed for screening against the inclusion and exclusion criteria . The forn = 2), not a systematic review (n = 1), could not access full text within the timeframe (n = 1), did not include veterans in the study population (n = 2), were focussed on interventions (n = 4) or were focussed on diagnosis and treatment (n = 1). An additional file includes the list of studies excluded at this stage of the review  then reviewed the included articles against the 11-item AMSTAR (A Measurement Tool to Assess Systematic Reviews) tool for measuring the quality of systematic reviews . The AMSn = 21; 71%), with no high and ten low quality reviews. The ten low quality reviews (scoring ≤4) were removed  and the recent Iraq and Afghanistan conflicts (Operation Enduring Freedom (OEF)/Operation Iraqi Freedom (OIF); n = 6), and veterans from particular countries (US: n = 8). Three reviews focussed on female veterans.Five reviews focussed on veterans in general. Other reviews focussed on veterans of particular wars, including the Gulf War  and assigned to the identified themes, with disagreements discussed and resolved. The number of reviews categorised into each of the identified themes is summarised in Table The literature is described below within each identified theme.n = 17; 81%). Mental health research relating to veterans has a strong focus on PTSD. Wall . However, as this rapid review demonstrates, a large number of veterans still experience mental, physical and social health problems related to life after the military, with the associated health care costs that come with this. The current review sought to better understand these needs to provide policy makers, service providers and healthcare professionals with an understanding of veterans’ wellbeing encompassing all three attributes of wellbeing . UnderstThe mental health literature demonstrates high rates of PTSD in veteran populations. The literature furthermore highlights the worrying interconnection between PTSD and the increased risks for veterans of physical health problems, substance use/ misuse, suicide, homelessness and aggression/ violence. However, the literature fails to adequately report on prevalence rates of mental health problems other than PTSD, and in particular to compare these rates to the general (civilian) population. Veterans clearly experience a range of mental health problems in addition to PTSD, particularly anxiety and depression, and comorbidy of mental health problems. However, as Blore et al.  noted in their review of depression in Gulf War veterans, “[t]he reality is that depression is often ignored in studies of veterans’ mental health, which tend to focus on PTSD”. The same can be said for anxiety and other mental health problems, and more systematic reviews focussing on these issues in the general population of veterans are needed, along with comparisons of rates between veteran and civilian populations.When considering the physical wellbeing of veterans, McLaughlin et al.’s  review sThe literature describing veterans’ social health furthermore articulates the potential difficulties of transitioning to civilian life post-military service , 50. ProWhen considering the literature describing the various factors associated with veterans’ mental, physical and social wellbeing, demographic factors in particular could help identify those veterans who might be at greater risk (though the question of why is still open for more research). There has been an increase in studies focussing on the issues facing female veterans, reflecting increasing numbers of women in the military and engaged in conflicts . Issues When serving in the military, individuals are provided with structured, comprehensive health care; care that is often no longer available after transitioning to civilian life, unless the veteran has been assessed as having ongoing healthcare needs related to their military service. Research with Vietnam veterans, for example, has shown that many do not have their healthcare needs recognised until several years after their return to civilian life, for a range of reasons including delays in help-seeking and delayed onset  . The resVeterans’ reported reluctance to seek help, particularly for mental health problems , 54, furBeing a rapid review of the literature, this paper is by definition limited by its short timeframe . HoweverIn this rapid review we have described the broad range of veterans’ mental, physical and social health care needs, in addition to the factors that affect the health and wellbeing of veterans. A key finding of the review is the interconnection between veterans’ physical, mental and social wellbeing. The findings therefore support the value of integrating veterans’ health care across the domains of physical, mental and social health in order to ensure that members of the military are taken care of both inside and outside of the uniform.


Vaginal intraepithelial neoplasia (VAIN) is a pre-malignant lesion, potentially leading to vaginal cancer. It is a rare disease, representing less than 1% of all intraepithelial neoplasia of the female genital tract. Similar to cervical intraepithelial neoplasia (CIN), there are three different grades of VAIN. VAIN 1 is also known as a low-grade squamous intraepithelial lesion (LSIL), whereas VAIN 2 and VAIN 3 both represent high-grade squamous intraepithelial lesions (HSIL). Risk factors for the development of VAIN are similar to those for cervical neoplasia, i.e. promiscuity, starting sexual activity at an early age, tobacco consumption and infection with human papillomavirus (HPV). However, compared to other intraepithelial neoplasia such as CIN or VIN , there still is little understanding about the natural course of VAIN and its capacity for pro- or regression. Furthermore, there is controversial data about the HPV detection rate in VAIN lesions.67 patients with histologically confirmed VAIN, who were diagnosed between 2003 and 2011 at the University Women´s Hospital of Heidelberg Germany, were included in this study. The biopsies of all participating patients were subjected to HPV genotyping. GP-E6/E7 Nested Multiplex PCR (NMPCR) was used to identify and genotype HPV. Eighteen pairs of type-specific nested PCR primers were assessed to detect the following "high-risk" HPV genotypes: 16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 66 and 68, as well as the "low-risk" genotypes 6/11, 42, 43 and 44. The data was analyzed with the software SAS .All 67 cases were eligible for DNA analysis. The median age was 53 years. The largest group with 53% (n = 36) was formed by women, who were first diagnosed with VAIN between the age of 41 to 60 years. 50% (n = 37) of the patients presented a VAIN in the upper 1/3 of the vagina. 58 (87%) were diagnosed with HSIL (VAIN). The median age in patients with LSIL (VAIN) was 53 years and in patients with HSIL (VAIN) 53.5 years. 12 women (18%) had an immunosuppression. HPV positivity was confirmed in 37 patients (55%). Except for a single patient, who had a triple infection with HPV types 6/11, 16 and 68, only infections with one single HPV genotype were detected. An infection with the HPV genotypes 31, 39, 45, 51, 58, 59, 66, 42, 43 and 44 couldn’t be found in any of the patients. In 28 patients with diagnosed VAIN, an infection with HPV 16 could be shown, 24 (86%) of them were diagnosed with a HSIL (VAIN). 16 (24%) women presented condylomata and 13 of them (81%) had a positive HPV status. However, only 47% of the women without condylomata presented a positive HPV status, resulting in a significant correlation (p = 0.0164) between condylomata and HPV infection. In 28 of all 67 patients (42%), recurrence of the neoplasia occurred.HPV 16 is the main virus-type to be associated with the development of a VAIN. Also, HPV 16 infection, VIN or condylomata acuminata in the past medical history seemed to be significant factors for early relapse. Vaginal intraepithelial neoplasia (VAIN) is a pre-malignant lesion, potentially leading to vaginal cancer. VAIN is rare, representing less than 1% of all intraepithelial neoplasia of the female genital tract .Similar to CIN, there are three grades of VAIN according to the depth of epithelial involvement. Whilst VAIN 1 only affects the lower one-third of epithelium, VAIN 2 involves the lower two-thirds and VAIN 3 more than two-thirds or the complete epithelium. VAIN 1 is also known as a low-grade squamous intraepithelial lesion (LSIL), whereas VAIN 2 and VAIN 3 both represent a high-grade squamous intraepithelial lesion (HSIL) [VAIN can affect women of any age, but it is more common in women above 50. Interestingly, age and grade of disease correlate in the sense that women of a higher age suffer from higher grades of VAIN . Risk faFurthermore, there is controversial data about HPV detection rate in VAIN lesions. Chao et al reported a 69.3% detection rate of HPV in VAIN lesions , whereas2 laser vaporization as a primary therapy. The treatment was done consistently between providers . We defined recurrence as detection of new lesions 8–12 weeks after initial therapy at earliest. In all cases the recurrence was histological confirmed by vaginal biopsy. All patients gave their written consent for analysis of their tissue. The study was approved by the ethical committee of the university of Heidelberg (S-277/2015).67 patients with histologically confirmed vaginal intraepithelial neoplasia (VAIN) and clinical examination between 2003 and 2011 at the University Women´s Hospital of Heidelberg, Germany, were included in this study. All patients were referred by the gynecologist to University Hospital due to a suspicious vaginal finding. VAIN was diagnosed according to guidelines, using colposcopy, followed by biopsy of the suspicious areas, which were revealed through application of acetic acid and Schiller's Iodine test. All parts of the vagina are thoroughly examined according to an examination scheme viewing the vagina clockwise starting at 3 o'clock. Hematoxylin-eosin sections were made from the biopsies and reviewed by an experienced pathologist. In uncertain cases, immunohistochemical analysis of p16 (INK4a) was additionally performed. We included only patients who were free of any suspicious area 8–12 weeks after initial diagnose or treatment. According to the WHO classification preinvasive lesions of the vaginal squamous epithelium are differentiated into LSIL (VAIN 1) and HSIL (VAIN 2 and 3) [Before HPV-testing all biopsies were reviewed by an independent pathologist. Data regarding the patient’s history and neoplasia status were collected retrospectively from the clinical documentation system. The biopsies of all patients, who were included in this study were subjected to HPV genotyping. GP-E6/E7 Nested Multiplex PCR (NMPCR) was used to identify and genotype HPV . The pri®, NORMAPUR®, VWR, Vienna) was added and heated to 55°C. After 10 minutes, the liquid was removed and the previous step repeated. Next, xylol was replaced by 100% ethanol and the samples were left to rest for 10 minutes twice. Between each step, the tissues were centrifuged at 13300G. After removal of alcohol, the tissues were incubated at 37°C. 0,788g Tris-HCl , 0,0372g EDTA  and 0.5 ml Tween 20  were added to a vessel. 50 - 75ml distilled water was added to the mixture and adjusted to a pH of 8.5. 5μl proteinase K  was added. The samples were then incubated overnight at 56°C. The next day the product was heated to 95°C for 5 minutes. As a next step 5μl were removed from this solution and transferred to a glass cuvette. Eventually, the DNA concentration was determined photometrically (NanoDrop ND-1000 Spectro Photometer). Subsequently, the solution was diluted with nuclease-free water  to 50ng/μl, after which 2.5 μl DNA were extracted for PCR.The samples, embedded in paraffin, were cut with a layer thickness of 7μm. Xylol  and 0,75μl 6P primer (10μM)  and 12,5μl "MasterMix" consisting of deoxynucleotide, Mg2+, 10-fold concentrated polymerase buffer solution, water and Taq polymerase. The Taq activation and denaturation of the DNA took place when heated to 94°C, in the first step for 4, then repeated for 1 minute. The primer hybridization was carried out at 40°C for 1 minute, the elongation phase at 72°C for 2 minutes initially and then again for 5 minutes. A total of 40 cycles were performed.2,5μl DNA were assessed with 9,25μl water  and 12,5μl "MasterMix" were added to 0,5μl E6/E7 product. The Taq activation and denaturation of the DNA were carried out again at 94°C for an initial 4 minutes, then again for 30 seconds. The primer hybridization took place at 56°C for 30 seconds. Finally, the elongation phase was carried out at 72°C, initially for 45 seconds, and in a second step for 4 minutes. A total of 35 cycles were performed.Separation of nucleic acid strands allows determination of the amplicon length, which leads to specific identification of HPV types. The agarose powder (3g to 100ml buffer) was dissolved in 1 × Tris-borate-EDTA (TBA) buffer and heated to near-boiling point. After brief cooling, 10μl "Gel Red" per 100ml buffer was added. The solution was poured into a cast, after which a comb was placed to create wells for loading. Next, the gel was layered with 1x TBE buffer in an electrophoresis chamber and loaded. Furthermore, 5μl PCR product with 2μl 40% glycerol were added on a microtiter plate and applied to the gel. As a molecular weight marker served 50 bp. The term was 1 hour at a voltage of 100 volts. Finally, the gel was removed from the chamber and photographed under UV light.Data were analysed with the software SAS . Categorical variables were compared by chi-square test or Fisher's exact test. p-values < 0.05 were considered statistically significant. Due to the small number of cases and partially missing values a multivariate analysis was not performed .All 67 cases were eligible for DNA analysis. The median age was 53 years (range 26–84 years). Subgroup analysis revealed a median age in patients with LSIL (VAIN) of 53 (range 28–66 years) and HSIL (VAIN) of 53.5 years (range 26–84 years). The largest group with 53% (n = 36) was formed by women, who were first diagnosed with VAIN between the age of 41 to 60 years. 50% (n = 37) of the patients presented with VAIN in the upper 1/3 of the vagina. 58 (87%) were diagnosed with HSIL (VAIN). According to conventional histology, only 6 cases were unclear, which meant that additional p16 (INK4a) staining was necessary. In all 6 cases p16 (INK4a) was detectable. In two cases no HPV infection could be shown, both patients had a HSIL. Three patients were HPV16 and one patient HPV 33 positive. Overall positive HPV status was confirmed in 37 patients (55%). 6  patients with LSIL (VAIN) were HPV positive and 31  of the patients with HSIL (VAIN). The median age of the group with detected HPV infection was 53 years (range 26–79). It differs only slightly from that of the HPV negative group . Detailed patient characteristics are shown in 12 women (18%) had an immunosuppression—4 of those received chemotherapy, 2 had an HIV infection, 3 suffered from diabetes mellitus type 1 or 2, and 3 patients had an autoimmune disease or history of transplantation with immunosuppressant medication.Except for a single patient who had a triple infection with HPV types 16, 6/11 and 68, only infections with one single HPV genotype were diagnosed. The genotype distribution is shown in 17 patients of this study presented a simultaneous or previous VIN. Twelve (71%) of those developed VAIN recurrence, whilst only 16 of the 50 patients (32%) without a VIN in the medical history did (p = 0.0053). 32 patients (48%) presented a simultaneous or previous cervical intraepithelial neoplasia (CIN). 10 patients of those patients developed a recurrence. In 18 of 35 patients without CIN the VAIN recurred . In 10 out of 16 women with a VAIN recurrence a history of condylomata was known . In one patient a vaginal carcinoma could be found with first diagnose of VAIN.Patients underwent follow-up examinations with a median duration of 12.5 months . A follow-up examination was scheduled every 2–3 months. In 28 of 67 patients (42%) recurrence of the VAIN occurred .Of the 28 patients, who suffered a recurrence, 20 (71%) had an HPV infection. In comparison, only 17 of the 39 (44%) recurrence free women had a HPV infection (p = 0.0238), indicating a significant correlation between HPV infection and recurrence of disease.The median time from initial diagnosis to recurrence was 12 months (range 3.3 months to 48.1 months). Of 58 patients with HSIL (VAIN), 25 (43%) developed a recurrence. Recurrent vaginal intraepithelial neoplasia was highly related to HPV infection . Only one patient progressed to vaginal carcinoma after one year. None of the other patients progressed to a higher grade of VAIN.The only patient with a low-risk HPV type 6/11 infection remained recurrence free, as well as two patients with HPV type 56. A significant correlation between HPV 16 infection an VAIN recurrence could be found. 16 (57%) out of 28 patients with a HPV 16 infection VAIN was recurrent (p = 0.0351). Also patients with HPV types 18, 33, 35 and 52 respectively, developed a recurrence. Furthermore, the women with a triple HPV infection with types 16, 6/11 and 68 also developed a recurrence.In accordance with other studies we were able to demonstrate that the median age of women suffering from VAIN was 53 years , 14. FurOther studies have revealed that VAIN is most frequently localised in the upper third of the vagina , 15. ThiAccording to the study of Dodge et al., a strong association between VAIN and coexisting CIN or VIN was present in 65% and 10% of cases, respectively .In addition, 25% of patients were either simultaneously diagnosed with VIN or had a VIN in the past and 48% of patients were diagnosed with CIN respectively. In summary, VAIN frequently presents not as a single pathological phenomenon in 60% of patients it is accompanied with other intraepithelial neoplasia of the lower genital tract. Patients with immune deficiency show a higher risk for developing multiple lesions of the lower genital tract –19, whicThere are heterogeneous results concerning the association of VAIN and HPV infection rate. Regarding to this diversity, non-standardised and differing approaches in HPV identification seem to be the leading issue. Smith et al reported a HPV identification rate of 98,5% in 66 LSIL (VAIN) cases and 92,6% in 166 HSIL (VAIN) cases . In contThe cellular tumor suppressor gene p16 (INK4a) is an important biomarker for HPV-associated intraepithelial neoplasia. Klaes et al. found an overexpression of p16(INK4a) in all examined LSIL (CIN) lesions—except for those being caused by "low-risk" HPV types—as well as in all HSIL (CIN) lesions. There was no expression in healthy cervical epithelium or inflammatory altered epithelium . In thisSimilar to the HPV detection rate, our HPV type analysis revealed different data compared to previous reports. The most common type of HPV in VAIN lesions is generally believed to be HPV 16. De Vuyst et al described HPV 16 in 57,6% of HSIL (VAIN) cases, Smith et al even showed a rate of 65,8% [Condylomata acuminata represent the most common benign genital tract tumours, originating from infection with low risk HPV types such as HPV type 6 and 11 . HistoloThe prevalence of vaginal carcinoma varies in different areas. Whereas in Eastern and Western Asia the prevalence rate is 0,2/100000, in Southern Asia and the Caribbean seems to be a higher prevalence rate  due to high HPV infection rate , 25. IrrFor some authors a premalignant or malignant cervical lesion is an stronger indication for hysterectomy –29 than However, the closer follow-up of these patients after hysterectomy due to intraepithelial neoplasia may partially cause this difference in the mean development time of VAIN as those patients might be monitored more closely.In the past there have been several attempts to identify risk factors for relapse, such as nicotine abuse, grading of VAIN, localisation, age and many others . NeitherHPV 16 is the main virus-type to be associated with the development of VAIN. Also, repeated HPV 16 infection, VIN or condylomata acuminata in the past medical history seem to be significant risk factors for relapse.S1 Table(XLSX)Click here for additional data file.S2 Table(RTF)Click here for additional data file.S3 Table(RTF)Click here for additional data file.S4 Table(RTF)Click here for additional data file.S5 Table(RTF)Click here for additional data file.S6 Table(DOCX)Click here for additional data file.


To study the concordance between vaginal self- and endocervical physician-collected high-risk (hr) HPV testing in Thai women who attended a colposcopy clinic. Vaginal samples were obtained by self-sampling with a dry brush before endocervical samples were obtained by physicians. Both specimens were analyzed for hrHPV by Cobas4800 HPV test.P < 0.001). Our study revealed moderate agreement between self- and physician-collected methods for hrHPV testing.Of the 247 pairs of samples, overall hrHPV prevalence from self- and physician-collected samples was 41.3 and 36.0%, respectively. The overall agreement between the methods was 74.5% with κ 0.46 ( Worldwide trends in incidence and mortality rate of cervical cancer have decreased as a result of effective organized screening programs, however, cervical cancer remains an important health problem in less-developed countries. In Thailand, it is the second most common cancer in women, with an age-standardized incidence rate of 17.8 per 100,000 .The Ministry of Public Health in Thailand launched a national screening program for women aged 30–60 years since 2002 but the coverage rate was 46–67%, which was lower than the target of 75% [Human papillomavirus (HPV) testing was approved for primary screening because of its satisfactory sensitivity for detecting high-grade precancerous cervical lesions –10. SelfDue to the uncommon use of tampon among Thai women, most of them are unfamiliar with inserting the device into their vagina. From our previous study, there was a concern that some women might not use the self-sample device properly . There hThe study protocol was approved by the Institutional Review Board of Chulabhorn Hospital (No. 10/2013). We recruited women aged 30–70 years who visited a colposcopy clinic at Chulabhorn Hospital, Bangkok, Thailand during March 1 to June 30, 2015. Women were eligible for inclusion if they were attending the colposcopy clinic, aged 30–70 years, had no history of cervical cancer, had not undergone a hysterectomy, and were currently not pregnant.After the participants had given written informed consent to participate in the study, they received instructions by video made by research project’s staffs to explain how to use the vaginal self-sampling brush, verbal and illustrations for vaginal self-sampling. The vaginal specimens were first obtained by self-sampling with the Evalyn Brush , which is a dry brush. Then, the participants were examined by a gynecological oncologist who obtained an endocervical sample with a Cervex-Brush .The self- and physician-collected specimens were both suspended in 10 ml transport medium, SurePath Preservative Fluid .All self-sampled and physician-collected specimens were sent to the central laboratory of Chulabhorn Hospital for hrHPV testing. All samples were analyzed by Cobas4800 HPV test  within 1 week after collection.Frequency, percentage, mean and standard deviation (SD) were used to calculate the general characteristics. The agreement levels were analyzed by Cohen’s kappa statistics. The statistical significance level was at 0.05. All data were analyzed by STATA/SE version 12.1.We enrolled 250 eligible women. Two participants were excluded because of a history of cervical cancer and previous hysterectomy. One pair of samples was excluded because of invalid test results. The mean and median ages of the remaining 247 participants were 47.2 and 47.0 years , respectively. Table Overall hrHPV prevalence was 41.3% 102/247) from self-collected specimens and 36.0% (89/247) from physician-collected specimens. The prevalence of hrHPV 16, 18 and non-16, 18 from self- and physician-collected specimens is shown in Table /247 fromThe concordance of hrHPV test results between self- and physician-collected specimens is shown in Table We found that the prevalence of hrHPV from self-collected specimens (41.3%) was higher than from physician-collected specimens (36.0%). To explain, the self-collected specimens are a combination of cervical and vaginal cells. Additionally, the sampling order first obtained from the self-collected specimens may then collect higher number of exfoliated cells. In particular, the higher prevalence of low-risk HPV in the lower vagina than in the cervix and scanty cross-reactivity of the hrHPV assay to low-risk genotypes can partially explain this finding , 29.Our study revealed 74.5% concordance between self- and physician-collected specimens in detecting overall hrHPV with κ 0.46, which showed moderate agreement. The level of agreement in our study was not as high as that in most previous studies –25. MostOne study showed that the agreement between these two methods was lower among older women, which supports our results . The medAlthough the agreement level of overall hrHPV between self- and physician-collected samples was moderate, the agreement level of HPV 16 was substantial, with concordance of 93.36% and κ 0.72. This finding for HPV 16 was the same as in the other studies , 25. As All the participants in our study did the self-collection first then underwent pelvic examination to obtain physician-collected specimens later. This sampling order may have resulted in the self-collected specimens having more exfoliated cells than the physician-collected specimens had.Our participants were women who attended a colposcopy clinic for various reasons such as abnormal cytology or positive HPV testing, so the prevalence of HPV in this group was higher than in the normal population. The prevalence of hrHPV in our study was 41.3 and 36.0% from self- and physician-collected specimens, respectively. The prevalence of hrHPV in Thai women in previous studies was 3.3–14.0% –36.Due to the level of agreement in our study was slightly lower than in most previous studies, more studies with larger populations are needed to explore the reliability and feasibility of self-sampling of HPV as a method for cervical cancer screening in Thai and other Asian women. The molecular and biomarker analyses may be combined to achieve greater accuracy of the test.


HPV) vaccines offer primary prevention of cervical cancer and protection against other HPV‐associated cancers. HPV vaccine coverage in the United States (U.S.) remains low, particularly among older adolescents/young adults, and the uninsured. We assessed awareness and knowledge of HPV disease, HPV‐related cancers, and HPV vaccines among working, uninsured adults. Data from the 2014 Health Information National Trends Survey  were used as a benchmark. Patients were surveyed in late 2014 at the Volunteers in Medicine free clinic in Duval County, Florida. Surveys contained validated measures of HPV disease and vaccine knowledge; HPV‐related cancer knowledge was also assessed. Two‐hundred and ninety‐six surveys were analyzable with an 84% participation rate. Half (50.3%) of participants had heard of HPV, and 32.1% had heard of the HPV vaccine; in HINTS, these estimates were 63.6% and 62.7%, respectively (both P < 0.0001). In adjusted models, high HPV disease knowledge was associated with white race and increased education; high vaccine knowledge was associated with white race, increased education, and female sex. Recognition of HPV as a causative agent was 43.9% for cervical, 9.1% for anal, and 11.1% for throat cancers. For all HPV‐associated cancers, participants had lower knowledge/recognition relative to HINTS. The uninsured, socioeconomically disadvantaged adults we surveyed were unaware of a ubiquitous virus that can cause cancer and the existence of a vaccine to protect against it. These findings point to settings and populations in which initiatives to promote HPV vaccination as a cancer prevention tool remain critical.Human papillomavirus ( Human papillomavirus (HPV) is a causative agent in cervical, anal, oropharyngeal, penile, and vaginal/vulvar cancers Licensed, safe, and effective vaccines to protect against new HPV infections, including types 16 and 18, are currently available; these include bivalent, quadrivalent, and nonavalent vaccines, each initially licensed for administration according to a 3‐dose schedule. In 2014, the World Health Organization reviewed noninferiority data and evidence from studies with alternative dosing regimens Reasons for poor HPV vaccine coverage in the United States have been described and include parent‐related factors, with ‘lack of knowledge’ and lack of physician recommendation being primary reasons cited among parents for not vaccinating their children The President's Cancer Panel report identified the need to increase HPV vaccination as a public health priority and outlined three goals toward achieving increased HPV vaccination coverage in the United States: reducing missed clinical opportunities to recommend and administer HPV vaccines; increasing acceptance of HPV vaccination; and maximizing access to HPV vaccination services This cross‐sectional, community‐based study was approved by the Institutional Review Board of Mayo Clinic and conducted at the Volunteers in Medicine Clinic (VIM) in Jacksonville, Florida (FL). The VIM clinic provides free primary care for working individuals without insurance who meet certain income requirements and live and/or work in Duval County, FL. Health care providers at VIM include volunteers who practice at other local health care organizations, in addition to full time staff. Approximately 1800 adult patients are seen annually; a majority (about 70%) of patients are female and over half are members of racial or ethnic minority groups. Currently, HPV vaccination is not offered at VIM due to cost considerations and a low volume of pediatric/adolescent patients.The content of the survey was informed by general knowledge of the clinic population and review of existing measures of HPV vaccine attitudes and knowledge. Demographic characteristics included sex, age, race, ethnicity, marital status, employment status, number of children, and formal educational attainment. Awareness of HPV was assessed by a “Yes” or “No” response to the question: “Before today, had you ever heard of human papillomavirus (HPV)?” Those responding “yes” completed a 16‐item validated HPV knowledge measure assessing disease knowledge developed by Waller and colleagues Surveys were developed in English and translated into Spanish by a certified translator using translation and back‐translation techniques. The Spanish translation was subsequently reviewed locally for language appropriateness; this process resulted in minor modifications. The survey content and data collection methodology were pilot‐tested for a 1‐week period in VIM . Pilot‐testing demonstrated feasibility of recruitment (91% eligible patients were offered a survey by clinic staff), acceptability of a research survey in this setting (84% participation rate), and informed changes to the survey design and layout for ease of completion.Volunteers in Medicine staff recruited a convenience sample of patients attending clinical appointments during the study period . Patients who were not in acute distress, understood English or Spanish, and provided oral consent to participate in a research study were offered a survey. Patients who returned a survey received a thank you gift and the HPV Fact Sheet developed by the Centers for Disease Control and Prevention.Data from the 2014 Health Information National Trends Survey  regarding HPV knowledge and vaccine awareness were used as a national benchmark against which to compare data from the VIM sample. HINTS is a nationally representative survey of the U.S. adult population focused on cancer‐related knowledge, attitudes, and behavior P < 0.05 level.Demographic characteristics were assessed overall and for those who had heard of HPV and the HPV vaccine. All three knowledge scores were created by equal weight summation. Furthermore, if survey participants responded as being unaware of HPV or the HPV vaccine, their respective knowledge scores were imputed to zero. High knowledge for HPV disease, HPV vaccines, and HPV‐related cancer was defined as having a knowledge score in the upper quartile of positive values (≥75th percentile of knowledge scores ≥1). Odds ratios (OR) and 95% confidence intervals were estimated using logistic regression to assess the association of demographic characteristics with having high knowledge (as defined above) of HPV disease, HPV‐related cancers, and the HPV vaccine, respectively. Additionally, estimates of association were derived for each individual cancer comprising the HPV‐related cancer knowledge score. Proportions on the benchmark items were calculated and tested using a one‐sample proportion test. The null hypothesis being that the VIM proportion equals the national benchmark (HINTS) estimate. HINTS data were weighted to provide estimates of the U.S. population as well as correct for nonresponse bias. All analyses were performed using SAS 9.4. Statistical comparisons were two‐sided and were considered significant at the During the study period, a total of 356 patients were eligible to participate. Of these, 301 patients accepted a survey and 55 declined (84% participation rate). Of the 301 surveys returned, five were excluded from analysis due to excessive missing data; a total of 296 surveys were included in the analyses. While the study participants were all adults, 230 (79%) indicated that they had children. Of 183 participants who indicated their children's age, 111 (61%) had at least one child who would be age‐eligible for HPV vaccination (ages: 9–26). http://factfinder.census.gov/faces/tableservices/jsf/pages/productview.xhtml?src=CF).The study sample closely reflected the overall demographics of the VIM patient population (described above). Specifically, 78% of the sample was female, 51% were black or African American and 10% were Hispanic, with a median age of 49 years. Additional demographic characteristics are shown in Tablen = 149) of the sample reported they had heard of human papillomavirus or HPV, and 32.1% (n = 95) had heard of a vaccine to protect against HPV (such as Gardasil or Cervarix) (Table P < 0.0001).Overall, 50.3% n = 49 of the P = 0.067).HPV disease, HPV vaccine, and HPV cancer‐related knowledge questions ranged from 0 to 16 items, 0–7 items, and 0–7 items, respectively. For patients who were aware of HPV or the HPV vaccine, the median  correct was 7 2, 10), 3 , and 1  for HPV disease, HPV vaccine, and HPV cancer knowledge, respectively. In adjusted models, whites and those with more education were more likely to have high HPV disease knowledge. Similarly, whites, females, and those with more education were more likely to have high HPV vaccine knowledge  answering correctly that HPV can cause cervical cancer. Importantly, only 9.1% (n = 27) of respondents marked the correct answer (“True”) for “HPV can cause anal cancer.” When benchmarked against national estimates obtained in HINTS 2014 data, VIM survey respondents were less knowledgeable of HPV as a cancer‐causing agent for each of the cancers that were included in both surveys (Table n = 77) of VIM survey respondents gave the correct answer of “False” to the item “HPV can cause lung cancer” and less than one‐quarter correctly answered “False” to the item “HPV can cause breast cancer.” Associations between demographic characteristics and correct knowledge of individual cancers revealed only sex/gender associations for cervical  and vulvar/vaginal cancer  such that females were more likely to answer these items correctly. Similarly, nonwhites were less likely to have correct knowledge of lung and skin cancers. Also, those with more than a high school education were more likely to have correct knowledge of cervical, vulvar, prostate, anal, lung, and skin cancers (results not shown).With regard to the knowledge items addressing specific cancers, knowledge was greatest for cervical cancer, with 43.9%  that have disproportionately lower HPV vaccine coverage and higher rates of several HPV‐associated cancers http://www.asco.org/sites/www.asco.org/files/nci_hpv_consensus_statement_012716.pdf).Decades of work in cancer prevention, early detection, and treatment have resulted in declining death rates for many cancers in the United States; however, the gains afforded by such efforts have not been equally enjoyed by those belonging to economically and socially disadvantaged groups Prior research suggests that educational efforts emphasizing the diseases that vaccines prevent may be more effective in reducing vaccine hesitancy than educational interventions aimed at dispelling misconceptions about the vaccine This study reveals gaps in knowledge and awareness of HPV vaccines in a United States sample of uninsured, socioeconomically disadvantaged adults when benchmarked against national estimates obtained during the same year. These gaps in knowledge potentially exist in other, similarly disadvantaged groups in the United States more than 10 years after the vaccine was licensed for use among females, and several years after being recommended for males. Our findings suggest that some of the most vulnerable individuals remain unaware of a ubiquitous virus that can cause cancer and the existence of a safe and effective vaccine to protect against it. These findings, while not without the limitations associated with a convenience sample of relatively small size obtained from a single clinic setting, are important and point to settings and populations in which HPV vaccine initiatives remain critical.None declared.


Plasmodium vivax, as well as the onward transmission of Plasmodium falciparum. However, primaquine can cause haemolysis in individuals who have glucose-6-phosphate dehydrogenase deficiency (G6PDd). We conducted a systematic review on the reported clinical manifestations of G6PDd to provide a comprehensive overview of the situation in the GMS.To achieve malaria elimination in the Greater Mekong Subregion (GMS) by 2030, proper case management is necessary. 8-aminoquinolines, such as primaquine, are the only available medicines effective in preventing relapse of the hypnozoite stage of The protocol for this systematic review was registered on PROSPERO: International prospective register of systematic reviews (CRD42016043146). We searched the PubMed/MEDLINE, CINAHL, and Web of Science databases for published articles describing the clinical manifestations of G6PDd in the GMS. We included articles of all study designs from inception until 31 July 2016, reporting the clinical manifestations of G6PDd. We then performed a narrative synthesis of these articles.We included 56 articles in this review, 45 of which were from Thailand. Haemolysis in G6PD-deficient individuals was caused not only by primaquine but also by other medicines and infections. Other clinical manifestations of G6PDd that were found were favism, neonatal jaundice and chronic non-spherocytic haemolytic anaemia. G6PDd also influenced the clinical presentations of genetic disorders and infections, such as thalassemia and typhoid fever.As G6PDd also affects the clinical presentations of other infections, the benefits of G6PD testing and proper record keeping transcend those of malaria case management. Therefore, healthcare workers at the community level should be made familiar with complications resulting from G6PDd as these complications extend beyond the scope of malaria. Primaquine plays an important role in malaria elimination.Primaquine is contraindicated in individuals with glucose-6-phosphate dehydrogenase (G6PD) deficiency.Testing for G6PD deficiency has the potential to help healthcare workers provide proper treatment to patients with malaria who are G6PD-deficient.Testing for G6PD deficiency and proper record keeping are effective in helping healthcare workers make informed decisions about providing treatment to patients with malaria.G6PD deficiency also affects the clinical presentation of other infections such as dengue fever and typhoid fever; therefore, the benefits of G6PD testing and proper record keeping go beyond the management of malaria.To avoid jeopardising the lives of G6PD-deficient individuals, their G6PD status should be determined before primaquine prescription.Systematic G6PD screening and proper record keeping of the most at risk populations are recommended.Training healthcare workers and equipping local facilities to enable better management of complications due to G6PD deficiency are recommended.Glucose-6-phosphate dehydrogenase (G6PD) deficiency is the most common enzyme deficiency in the world, affecting over 400 million people.1 2The WHO classifies G6PDd into five different categories according to the severity of enzyme deficiency.1 3The two most common G6PDd variants are the G6PD A- and G6PD Mediterranean variants.5 6Plasmodium vivax and Plasmodium ovale, and the onward transmission of Plasmodium falciparum.7Acute haemolysis can occur in a G6PD-deficient person who is exposed to antimalarials from the 8-aminoquinoline family.2 and sustains over 326 million people.P. falciparum malaria parasite.P. vivax is extremely resilient to elimination due to the dormant hypnozoite stage which occurs in the liver and the parasite's ability to spread via mosquitoes before the onset of clinical symptoms. Therefore, proper utilisation of an antihypnozoite such as primaquine to eliminate malaria is warranted.12The Greater Mekong Subregion (GMS) comprises Lao People's Democratic Republic (PDR), Thailand, Cambodia, Vietnam, Myanmar and Yunnan Province and Guangxi Zhuang Autonomous Region of the People's Republic of China. The GMS encompasses an area of 2.6 million kmG6PDd variants are diverse and each deficient individual can respond differently when exposed to oxidative stress caused by primaquine.Beyond malaria, G6PDd is also relevant in other contexts.15Despite the high burden of G6PDd in malaria endemic GMS, there remains a lack of data on the major clinical complications of G6PDd. Therefore, we conducted this review to identify the major clinical manifestations and complications of G6PDd in GMS countries.We prepared a protocol and registered it on PROSPERO: International prospective register of systematic reviews (CRD42016043146),  AND (Greater Mekong Subregion OR GMS OR Lao People's Democratic Republic OR Lao PDR OR Laos OR Thailand OR Vietnam OR Viet Nam OR Cambodia OR Myanmar OR Burma OR People's Republic of China OR Guangxi Zhuang Autonomous Region OR Yunnan Province OR Yunnan OR PRC).Tasks were divided equally among the five reviewers  for each stage of the review process, which included searching, screening and data extraction. We resolved all disagreements and conflicts through group meetings and discussions with the review team members.We included original research of all study designs, including clinical trials, cohort studies, case–control studies, cross-sectional studies, case series and case reports according to the following criteria: G6PDd was the target condition, G6PDd was identified after the manifestation of clinical symptoms, clinical information was available and the study population was from the GMS. We excluded review papers and studies on migrant populations from outside the GMS residing within the GMS.We used a standardised data extraction form  and nine were experimental  . In geneWe found a total of seven articles on primaquine-induced haemolysis.In a study in Cambodia on the tolerability of a 0.75 mg/kg of primaquine weekly regimen, a male patient with G6PDd developed clinically significant anaemia (a haemoglobin concentration of 7.2 g/dL) which required a transfusion.23A single dose of 45 mg of primaquine was given to seven healthy men in Thailand.22P. vivax infection. However, the patient was not tested for G6PDd and the instructions were not given in a language understood by the patient.A primaquine overdose case was reported on the Thai-Myanmar border.A total of nine articles mentioned infection-induced haemolysis.Four articles, three from Thailand and one from Lao PDR mentioned drug-induced haemolysis in individuals with G6PDd.We found two articles from Thailand that mentioned favism.37A total of four articles examined neonatal jaundice, all of which were from Thailand.40CNSHA was mentioned in two articles from Thailand.The second article provided details of two families affected by CNSHA, including the family of the previously mentioned boy with G6PD Bangkok.Seven articles described the dual burden of G6PDd and other infections or genetic disorders.44 48Eight articles examined the relationship between G6PDd and other haematological conditions.55A total of 11 articles discussed the effects of several antimalarial medicines on patients with G6PDd.One article from Thailand reported that highly active antiretroviral therapy did not cause haemolytic anaemia nor did it cause hyperbilirubinaemia in G6PD-deficient patients living with HIV.68Other findings on the clinical manifestations of G6PDd were described in four articles.72This systematic review has three major findings. First, the major clinical manifestation of G6PDd in the GMS was haemolysis induced by not only primaquine but also other medicines and infections. Second, favism, neonatal jaundice and CNSHA were reported as clinical manifestations of G6PDd. Finally, G6PDd affected the clinical presentations of genetic disorders and infections, such as thalassemia and typhoid fever.In two case reports from Thailand, two male patients were prescribed primaquine without G6PD testing.Knowing the G6PD status of patients might be beneficial not only in the context of malaria but also in the context of other infections such as typhoid fever, dengue infection and viral hepatitis. Haemolysis can also occur in G6PD-deficient patients who are coinfected with the abovementioned infections.Although favism is a primary manifestation of G6PDd,The lack of information on neonatal jaundice and G6PDd from GMS countries other than Thailand indicates that neonatal jaundice might be under-reported. Neonatal jaundice, which can lead to permanent brain damage in a condition called kernicterus, is one of the most devastating consequences of G6PDd.Even though CNSHA is a rare condition among people with G6PDd, the lack of information from other GMS countries besides Thailand might be due to under-reporting. The two variants described in the two studies were G6PD Bangkok and G6PD Bangkok Noi. The most serious form of infection-induced haemolysis was reported to be due to dengue haemorrhagic fever, which required blood transfusions.Treatment of complications resulting from G6PDd, such as blood transfusions, can be costly and require proper facilities and trained personnel. A cost study in Brazil estimated that the average cost of treatment of severe adverse events due to primaquine among patients with G6PDd is about US$4.8 million per year.Nevertheless, the evidence from this review should be interpreted with caution as we have only included papers published in the English language. Moreover, most studies we found were from Thailand. Consequently, the evidence here might not be exhaustive of all the clinical manifestations of G6PDd in the GMS. However, based on the predicted prevalence and predicted risk of haemolysis of the G6PDd variants in the GMS,78Prescription of primaquine should be preceded by prior assessment of a patient's G6PD status. Moreover, systematic screening and record keeping of G6PDd would be beneficial and cost-effective in the GMS. When trained healthcare workers properly manage severe adverse events, they can prevent the loss of life due to haemolysis in patients with G6PDd. Healthcare workers at the community level should be made familiar with symptoms and complications due to G6PDd and trained to take appropriate action such as referring a patient to a better equipped health facility. Finally, G6PD status is important not only in the context of malaria but also in the context of other infections such as typhoid fever and dengue fever, which are prevalent in the GMS.


Infection with human papillomavirus (HPV) is common and can progress to various types of cancer. HPV infection can be prevented through vaccination; however, vaccination rates among adolescents are low. The objective of this study was to assess efforts among Wisconsin stakeholders in HPV vaccination and organizational capacity for future collaborative work.We conducted a cross-sectional online survey of 277 stakeholders in HPV vaccination activities, from April 30, 2015, through June 30, 2015. Stakeholders were public health professionals, health care providers, educators, quality improvement professionals, researchers, and advocates identified as engaged in HPV vaccination work. Of the 277 invited stakeholders, 117 (42%) responded to the survey. Findings showed that most current HPV vaccination activities targeted 3 groups: adolescents and parents, clinical and health professionals, and communities and health systems. The main activities directed at these groups were providing printed educational materials, professional education, and media campaigns to raise awareness. Common barriers reported were lack of understanding about the link between HPV and cancer, requests to delay vaccination, difficulty completing the 3-dose vaccine series, and reluctance to discuss sexuality.HPV vaccination rates are far below those of other vaccinations administered to adolescents in Wisconsin. Our study showed that various local efforts were being made to increase HPV vaccination uptake; however, many barriers exist to initiation and completion of the vaccine series. Future interventions should address barriers and employ evidence-based strategies for increasing HPV vaccination rates. Human papillomavirus (HPV) infection is common, especially among young adults –3. AlmosThe Wisconsin Comprehensive Cancer Control Program, housed at the University of Wisconsin Carbone Cancer Center, was among 18 sites funded by the National Cancer Institute to conduct an environmental scan of HPV vaccination activities to enhance collaborations for developing research and interventions to increase HPV vaccination rates in Wisconsin . The scaWe conducted a cross-sectional online survey of 277 Wisconsin stakeholders in HPV vaccination activities from April 30, 2015, through June 30, 2015 . StakehoStudy participants reported on their role in their organization and answered other organization-related questions, including type of organization, whether the organization belonged to a local or regional immunization coalition, whether the organization accessed the Wisconsin Immunization Registry, and whether the organization used the Registry for Effectively Communicating Immunization Needs and an electronic health record to track immunizations. Respondents were also asked about their organization’s interest in conducting new activities and their capacity to take on new activities to promote HPV vaccination.Respondents were asked whether their organizations conducted any activities in Wisconsin in 2013, 2014, or 2015 related to HPV vaccination. The activities were classified into 4 categories:1) adolescents and their parents, 2) clinical and health care professionals, 3) communities and health systems, and 4) advocacy and public policy. If respondents reported activities in any year in any of these categories, they were asked to provide information about how often they encountered certain barriers . The selections of sometimes, often, and always were defined as barriers. In addition, respondents provided information on their funding sources and collaborating organizations for each category of activities.P less than .05.We calculated simple descriptive statistics to examine the prevalence of HPV vaccination-related activities that stakeholders conducted from 2013 through 2015 and the barriers they encountered. We then tested for trends in different activities over time. All analyses were performed with Stata/MP version 13.1 (StataCorp LP). Significance was set at Of the 277 stakeholders we invited to participate, 117 replied, a response rate of 42.2%. Of the 117 stakeholders who participated in the survey, 37 (31.6%) classified themselves as public health professionals, 21 (17.9%) as health care providers, and 9 (7.7%) as educators . Thirty P < .05) (Stakeholders reported on activities that their organizations conducted in recent years to increase HPV vaccination. Ninety-four (80.3%) reported that their organizations were involved in activities focusing on adolescents (girls or boys aged 11–18 y) and their parents. In 2015, the most common activities involving adolescents and their parents were providing printed educational materials (69.2%), one-on-one consultations to adolescents and parents on HPV vaccination (54.7%), reminders to adolescents and parents of when adolescents were due for HPV vaccination (47.9%), and referrals to HPV vaccination services (46.2%). The pattern was similar for 2013 and 2014, and the prevalence of these 4 types of activities increased significantly over time (P < .05) .Overall, 75 respondents reported barriers to activities focusing on adolescents and parents. The most common barriers were lack of education or understanding about HPV infection, including its link to cancer (86.6%); logistical or other barriers to returning for the full series of 3 shots (74.7%); requests that HPV vaccination be deferred (71.7%); belief that the adolescent is not at risk for HPV infection (71.6%); and the parent’s belief that child is too young for the HPV vaccine 68.5%, .P < .05). Barriers most often encountered by these organizations (N = 54) were difficulty ensuring that patients completed the 3-dose HPV vaccination series (63.0%), concern that parents would decline HPV vaccination despite appropriate counseling (57.7%), reluctance to discuss sexuality or sexually transmitted infections (45.3%), concern about the time it takes to discuss HPV vaccination with patients or parents (41.5%), and HPV vaccination not being required by schools (37.1%) (Seventy-six of the 117 respondents (65.0%) indicated that their organizations were conducting activities focusing on clinical and health professionals to increase HPV vaccination. The most commonly reported activities in 2015 were providing printed educational materials (53.0% of stakeholders), professional education on HPV vaccination (47.0%), protocols to track and report on HPV vaccination rates (35.0%), and websites focused on health professionals (11.1%) . The inc (37.1%) .P < .05). Barriers experienced in implementing community- and health-system–focused activities (N = 43) were lack of education or understanding about HPV infection, including its link to cancer (44.1%); difficulty ensuring that patients will complete the 3-dose HPV vaccination series (41.9%); belief that younger adolescents are too young for the HPV vaccinations (41.8%); and reluctance to discuss sexuality or sexually transmitted infections (38.7%) (Sixty-one stakeholders (52.1%) identified their organization’s activities as projects focusing on communities and health systems. The most commonly reported activity in this category in 2015 was media campaigns to raise awareness about the need for HPV vaccination of adolescents , followed by community committee or work groups that focus on HPV vaccination (24.8%), support for community groups that fund and promote the vaccine (23.1%), and community events or health fairs to promote HPV vaccination (21.4%) . The inc (38.7%) .P < .05)  indicated that they were involved in activities focused on advocacy and public policy with the most commonly reported activity in 2015 being efforts to increase HPV vaccination rates through advocating public policy change (17 respondents), followed by advocating for increasing public funding for HPV vaccination (13 respondents) and advocating for increased public funding for HPV research (5 respondents) . The rates of the former 2 activities increased over time (P < .05) . BarrierP < .05) Most organizations reported working with partners on activities promoting HPV vaccination: activities that focused on adolescents and parents (50 of 94 respondents), activities that focused on clinical and health professionals (47 of 76 respondents), activities that focused on communities and health systems (37 of 61 respondents), and activities that focused on advocacy and public policy (14 of 18 respondents). Commonly reported collaborators were the Centers for Disease Control and Prevention (CDC), the Wisconsin Immunization Program, local health departments, local clinics and hospitals, schools, local immunization coalitions, the Wisconsin Comprehensive Cancer Control Program, and the Wisconsin chapter of the American Academy of Pediatrics. Primary sources of funding for HPV vaccination activities were CDC, the Wisconsin chapter of the American Academy of Pediatrics, the Wisconsin Department of Health Services, the University of Wisconsin Partnership Program, the Wisconsin Immunization Program, immunization coalitions, the Wisconsin Comprehensive Cancer Control Program, and tax levy funds.Persistent HPV infection can lead to cancer of the cervix, vulva, vagina, penis, anus, and oropharynx . The HPVhttps://www.dhs.wisconsin.gov/immunization/data.htm).As in other research, Wisconsin stakeholders reported several main barriers to vaccination across groups: lack of understanding about HPV and its link to cancer, reluctance to discuss sexuality, parental resistance to the vaccination, belief that the adolescent is too young or is not at risk, difficulty with completion of the 3-dose vaccine series, safety concerns, and concern about promoting risky sexual behavior ,19. HealA strength of our study is that it is the first statewide, comprehensive review of HPV vaccination activities in Wisconsin. A limitation is that our list of Wisconsin HPV vaccination stakeholders may be incomplete, and we do not have information about HPV vaccination-related activities conducted by stakeholders who were not identified. However, the participant list was reviewed by representatives of the Wisconsin Immunization Program, the Wisconsin chapter of the American Academy of Pediatrics, and the University of Wisconsin Immunization Taskforce to identify missing stakeholders engaged in current or recent HPV vaccination work who were then added to the group. Another limitation is that the survey response rate was moderate (42.2%), but it was within the range (40%–60%) recommended for surveys to inform key policies and resource allocation . A compa