We investigated whether military personnel involved in chemical warfare agent research at Porton Down had increased rates of mortality or cancer incidence.This was a historical cohort study comprising male UK veterans who participated in the ‘Service Volunteer Programme’, 1941–89, identified from Porton Down experiment books, and a comparison group of similar ‘non-Porton Down’ veterans identified from military personnel files. Of 19 233 records retrieved for each group, 18 133 (94%) Porton Down and 17 591 (92%) non-Porton Down were included in our analytical sample. Mortality and cancer incidence data were obtained from national registries up to December 2019.P = 0.006. There was no association between attendance at Porton Down and overall cancer incidence .Over a median follow-up of 48.1 years, 10 935 Porton Down veterans (60.3%) and 10 658 non-Porton Down veterans (60.6%) had died. After adjustment for age, year of birth and military service characteristics, overall, Porton Down veterans had a 6% higher rate of all-cause mortality compared with non-Porton Down veterans . For cause-specific mortality, Porton Down veterans had higher rates of death from genitourinary diseases  and deaths attributable to alcohol , with weaker associations observed for deaths from infectious and parasitic diseases , lung cancer  and external causes . Associations with all-cause mortality were stronger for veterans who attended Porton Down between 1960 and 1964 ; likelihood-ratio test, Overall, mortality rates were slightly higher in Porton Down veterans, but there was no difference in cancer incidence. Associations for mortality were stronger in Porton Down veterans who attended in the early 1960s. Key MessagesLittle is known about the long-term health effects of low-dose exposure to chemical warfare agents.UK military personnel who were involved in chemical warfare agent research at Porton Down between 1941 and 1989 were followed up for mortality and cancer incidence.Porton Down veterans had a slightly higher (6%) rate of all-cause mortality compared with non-Porton Down veterans, and there was no difference in cancer incidence; however, hazard ratios were raised for some specific causes of death and types of cancer.Associations for mortality were stronger in Porton Down veterans who attended in the early 1960s, compared with other attendance periods.Health providers should be aware of the specific health issues and concerns surrounding military personnel and others (e.g. civilians and emergency responders) who may have experienced exposure to chemical warfare agents.In response to the use of chemical weapons during World War I, the UK government began human and animal research at Porton Down, UK, to learn more about the development and effects of these agents and protective clothing and medical countermeasures. Since 1916, over 20 000 military service personnel have attended Porton Down as part of the ‘Service Volunteer Programme’,,The Porton Down Cohort Veterans Study was assembled in the early 2000s in response to concerns raised by former UK service personnel that their long-term physical and psychological health may have been affected by their involvement in the programme. Findings from the first phase of the study, which followed mortality and cancer incidence up to December 2004, found that Porton Down veterans had a 6% higher all-cause mortality rate but similar cancer incidence compared with non-Porton Down veterans.The Porton Down Veterans Cohort Study is the largest of its kind, and recently underwent a second phase of data linkage to include an additional 15 years of follow-up data.,The Porton Down Veterans cohort is a retrospective cohort study that comprises two sub-cohorts of military veterans: the ‘Porton Down veterans’—all those identified from historical records at Porton Down as having participated in the Service Volunteer Programme between 1 April 1941 and 31 December 1989; and ‘non-Porton Down veterans’—a comparison cohort of veterans who did not attend Porton Down and who were identified by selecting the adjacent service number (either above and below) of every Porton Down veteran. Military characteristics and demographic information were abstracted from military personnel archives. Further detail on assembly of the Porton Down Veteran and comparison cohorts can be found elsewhere.IJE online) shows 19 233 valid records were identified for both Porton Down and non-Porton Down veterans; 18 466 (96.0%) and 18 129 (94.2%), respectively, were successfully retrieved and contained sufficient information for linkage with National Health Service (NHS) Central Registry data. Of these records, 16 721 (90.5%) Porton Down and 16 228 (89.5%) non-Porton Down veterans were successfully traced.Information on mortality and emigration was obtained from the National Health Service Central Register (NHSCR). For untraced veterans, additional deaths were identified from the Commonwealth War Graves Commission, Department for Work and Pensions and military personnel records (5.7%).Cancer site and date of registration were available from national cancer registries from 1 January 1971. For cancers listed on the death certificate only, we used date of death as the date of cancer registration .,,Cause of death and cancer registrations were coded according to ICD-10 .n = 974). Follow-up time for mortality was until date of death or 31 December 2019, or was censored at the last known date alive .For mortality, person-years of follow-up for Porton Down veterans started from the date of their first test at Porton Down , year of birth, service at enlistment , previous duration of service (years), period of enlistment , and place of birth .Eligible cohort members were all UK servicemen who participated in the Service Volunteer Programme at Porton Down between 1 April 1941 and 31 December 1989, and their corresponding non-Porton Down veteran, who had complete data on mortality, start and end person-years of follow-up and covariates.n = 132) (IJE online). The analytical sample for mortality consisted of 18 133 Porton Down and 17 591 non-Porton Down veterans.In all, 18 441 Porton Down veterans and 17 846 non-Porton Down veterans were successfully traced or had first-phase study data; exclusions (308 Porton Down veterans and 255 non-Porton Down veterans) included those with missing or implausible data  and a small number of women (Prior to the start of follow-up for cancers (1 January 1971), 849 Porton Down veterans and 761 non-Porton Down veterans had died and 357 Porton Down veterans and 295 non-Porton Down veterans were lost to follow-up. The analytical sample for cancer incidence consisted of 16 927 Porton Down veterans and 16 533 non-Porton Down veterans.Kaplan–Meier graphs were used to compare the survival probability of those who did and did not attend Porton Down.All-cause and cause-specific mortality rates between Porton Down and non-Porton Down veterans were compared using Cox’s proportional hazards models, with time since start of follow-up as the time scale. Models were first adjusted for age (at start of follow-up) and calendar period (year of birth); and then further adjusted for military demographics . Since experimental programmes at Porton Down changed over time, we also examined associations between period of Porton Down attendance and mortality by 5-year bands; interactions were tested using likelihood ratio tests. We also conducted exploratory analysis examining whether specific chemical exposures to which at least 100 veterans were exposed accounted for the excess mortality observed in veterans who attended Porton Down between 1960 and 1964. Deaths 100% attributable to alcohol were defined by ICD-10 codes F102, K701, K703, K704, K709We calculated E-values for both the observed association estimates and the limit of the confidence interval closest to the null to assess the robustness of associations between Porton Down attendance and outcome variables.IJE online).Competing risk analysis provided similar but slightly attenuated estimates for key associations (P <0.05), so baseline hazard functions for these variables were allowed to vary by stratum (5-year bands).The proportional hazards assumption was tested using Schoenfeld residuals; the assumption was violated by age and calendar period .IJE online). The majority of veterans served in the Army, were born in England before 1940, and enlisted in their teenage years under periods of conscription, either during World War II (1939–45) or during ‘National Service’ (1945–60). Descriptive characteristics for veterans with complete data on cancer registrations were similar (IJE online).Descriptive characteristics for Porton Down veterans and non-Porton Down veterans were largely identical except for ‘total duration of service’; Porton Down veterans tended to serve for longer. For example, 27.8% of Porton Veterans served over 10 years, compared with 17.7% of non-Porton Down Veterans . Incidence rates for all-cause mortality were 13.0 per 1000 person-years for Porton Down veterans and 12.9 per 1000 person-years for non-Porton Down veterans. Kaplan–Meier survival curves show that Porton Down veterans and non-Porton Down veterans had comparable survival probabilities over time .Across all periods of attendance and after full adjustment, Porton Down veterans had a slightly higher mortality rate compared with non-Porton Down veterans  .P = 0.006) (IJE online). This association was not driven by any particular year between 1960 and 1964. Notably, Kaplan–Meier survival curves for Porton Down and non-Porton Down veterans only began to diverge, indicating differing rates of mortality, after approximately 25 years of follow-up (IJE online). Veterans were often exposed to more than one type of chemical  gas, pralidoxime, sarin or dibenzoxazepine (CR) gas were also exposed to sulphur mustard) so it was not possible to identify whether excess mortality was driven by a specific exposure(s).We observed stronger associations between Porton Down veterans and mortality among those who attended between 1960 and 1964 compared with other attendance periods , compared with non-Porton Down veterans. Most associations were unaffected by excluding those who attended Porton Down between 1960 and 1964.Across all periods of attendance, Porton Down veterans had higher rates of mortality from diseases of the genitourinary system  and deaths attributable to alcohol  compared with non-Porton Down veterans . Weaker In contrast to other attendance periods, veterans who attended Porton Down between 1960 and 1964 demonstrated stronger associations with death from: any malignant neoplasm , oesophageal cancers  and lung cancers ; all diseases of the circulatory system  and ischaemic heart disease ; and smoking related deaths .IJE online). Cancer incidence rates were almost identical: 10.0 per 1000 person-years for Porton Down veterans and 10.3 per 1000 person-years for non-Porton Down veterans, with Kaplan–Meier plots indicating similar survival probabilities over follow-up (IJE online).Over a median follow-up of 34.0 years (range 1 day to 49.0 years), 5396 (31.9%) of Porton Down veterans and 5475 (33.1%) non-Porton Down veterans had at least one cancer (P = 0.41).In fully adjusted models, there was no evidence of an association between Porton Down attendance and overall incidence of any neoplasm  or malignant neoplasms ; however, Porton Down veterans did have higher rates of neoplasms of ‘uncertain or unknown behaviour’ . Weaker associations were observed for neoplasms of the trachea, bronchus and lung  and all other primary malignant neoplasms . Porton Down attendance was also associated with lower rates of ‘other skin’ neoplasms  and ‘other urinary tract’ neoplasms  . There wCI) was 1.17 (IJE online). Larger E-values were observed for deaths from diseases of the genitourinary system  and alcohol attributable deaths . For attendance between 1960 and 1964, the E-value for all-cause mortality was 1.75 (ECI 1.51), with E-values ranging between 1.94 and 4.31 (ECI range 1.40–1.79) for deaths from malignant neoplasms, oesophageal and lung cancers, diseases of the circulatory system, ischaemic heart disease and smoking-related deaths. For cancer incidence, the E-values for ‘any neoplasm of uncertain or unknown behaviour’ were 1.86 (ECI 1.31).Across all periods of attendance, the E-value for the fully adjusted association between Porton Down attendance and all-cause mortality was 1.25 and the E-value for the limit of the confidence interval closest to the null (En = 18 133) had a 6% higher relative rate of all-cause mortality compared to non-Porton Down veterans (n = 17 591). For cause-specific mortality, Porton Down attendance was associated with higher rates of death from diseases of the genitourinary system (34%) and alcohol-attributable deaths (44%). Weaker associations were observed for deaths from infectious and parasitic diseases (32%), malignant neoplasms (5%), lung cancers (10%), circulatory diseases (6%), external causes (15%) and smoking-related deaths (7%). We found that the association between Porton Down attendance and mortality was stronger in veterans who attended Porton Down between 1960 and 1964 compared with other periods. Attendance during the early 1960s was associated with a higher rate of all-cause mortality (34%), deaths from malignant neoplasms (47%), diseases of the circulatory system (38%) and smoking related deaths (48%) compared with non-Porton Down veterans. There was little evidence of an association between Porton Down attendance and higher rates of overall cancer incidence, nor for most types of cancer.Across all periods of attendance, Porton Down veterans  could only be accounted for by an unmeasured confounder associated with both the exposure and outcome by a risk ratio of at least 2.24, and the confidence interval could be moved to include the null by an unmeasured confounder with a risk ratio of at least 1.34, above and beyond the measured confounders. We have no evidence that the prevalence of unmeasured confounders should be considerably higher in veterans who attended Porton Down compared with non-Porton Down veterans, as they were matched by the time and location of recruitment. Further, if the prevalence of, for example, smoking, alcohol misuse and social disadvantage were markedly higher in veterans who attended Porton Down, we would expect to see excess mortality across numerous outcomes typically associated with these factors.,Our results are consistent with those reported in the first phase of the Porton Down Veterans Cohort study, which followed veterans for mortality and cancer incidence until December 2004.n = 4487), exposed to chemical and biological agents, were found to have higher rates of all-cause mortality  and deaths from heart disease  compared with non-SHAD veterans, yet no associations were reported for other causes of death, including deaths from infectious and parasitic diseases  and external causes .,Several smaller US studies have examined the long-term health of military personnel who participated in chemical warfare agent research. Project SHAD (Shipboard Hazard and Defence) veterans  could be explained if Porton Down veterans who attended during this time were systematically different in some way due to their recruitment. Conversely, these results could suggest that their chemical exposures were unusual during this period, whether by dose or by type. Nearly 5000 tests involving 44 different chemicals were conducted during 1960 to 1964; it was not possible to establish whether excess mortality during this period could be ascribed to a single type of chemical(s) as exploratory analyses demonstrated that hazard ratios were raised for most chemicals to which at least 100 veterans were exposed, and veterans were often exposed to multiple types of chemical, making it difficult to establish whether excess mortality was driven by a specific exposure(s).Higher rates of deaths from cancers, and circulatory diseases observed in Porton Down veterans who attended in the early 1960s  and the Health Research Authority’s Confidentiality Advisory Group  under section 251 of the National Health Services Act 2006. For Scotland, approval was granted by the Public Benefit and Privacy Panel for Health and Social Care (PBPP-HSC). Data Sharing Agreements are in place with NHS Digital and the PBPP-HSC, which are reviewed annually.dyad050_Supplementary_DataClick here for additional data file.


To determine predictors of the association between being a Veteran and adult food security, as well as to examine the relation of potential covariates to this relationship.v. the combination of marginal, low and very low food security compared with non-Veterans.Data collected during 2011–2012, 2013–2014 and 2015–2016 National Health and Nutrition Examination Survey (NHANES) were pooled for analyses. Veterans (self-reported) were matched to non-Veterans on age, race/ethnicity, sex and education. Adjusted logistic regression was used to determine the odds of Veterans having high food security 2011–2012, 2013–2014 and 2015–2016 NHANES.1227 Veterans; 2432 non-Veterans.v. non-Veteran: 79 % v. 80 %), marginal (9 % v. 8 %), low (5 % v. 6 %) and very low (8 % v. 6 %) food security (P = 0·11). However, after controlling for covariates, Veterans tended to be less likely to have high food security , P = 0·07). Further, non-Hispanic White Veterans , P = 0·02) and Veterans completing some college , P < 0·05) were significantly less likely to experience high food security compared with non-Veterans.Veteran status had no effect on the proportion of food insecurities between Veterans and non-Veterans reporting high (Veterans This study supports previous research findings that after controlling for covariates, Veterans tend to be less likely to have high food security. It also highlights ethnicity and level of education as important socio-economic determinates of food security status in Veterans. Food insecurity also highlights another area of concern – a choice between paying for food and paying for medication. This dilemma leads to a higher risk for uncontrolled chronic health conditions and increased healthcare costs because of an inability to adhere to disease-specific diet modifications and medication treatment plans.Households that are food secure have access at all times to adequate food to stay healthy, whereas food insecurity, or the limited or uncertain access to adequate and appropriate food, is a multifaceted phenomenon independently associated with chronic health conditions. Despite being known for their resiliency during and following their military service, Veterans are more likely than non-Veterans to be disabled because of their unique exposures during military service. Furthermore, both male and female Veterans are significantly more likely to have multiple chronic health conditions compared with their non-Veteran counterparts. Having multiple chronic conditions is also associated with food insecurity in younger and older adults. Despite these risk factors suggesting Veterans are more vulnerable to food insecurity the findings regarding food insecurity in Veterans are currently inconsistent with reports of higher, lower and equivocal findings of food insecurity in the literature. Reports from the Current Population Survey Food Security Supplement for 2005–2013 outlined lower rates of food insecurity between Veterans (8·4%) and non-Veterans (14·4%), and pooled data from the 2012 Health and Retirement Study and 2013 Health Care and Nutrition Mail Survey reported similar rates of food insecurity between Veterans (6·4%) and non-Veterans (11·9 %). However, a recent 2021 economic research report by the US Department of Agriculture found that after controlling for undefined ‘observable differences’ in socio-economic, demographic and military characteristics, working-aged Veterans (18–64 years) were 7·4% more likely to live in a food insecure household than non-Veterans. These data highlight the need for further evaluation to understand the influence of prior military service on food security status.Disability has been identified as a risk factor for food insecurity, such that households with an adult unable to work due to a physical or mental health disability are three times more likely to experience food insecurity, since many have been linked to food security status previously–15. The understanding of socio-economic and biomedical factors associated with food security status in Veterans will aid in the development of interprofessional interventions and partnerships in clinical and community settings targeted to address the unique needs of the Veteran population.With a growing body of evidence finding socio-economic and biomedical differences between Veterans and non-Veterans , it is important to examine the impact these differences may have on food security status. However, these analyses were limited to Veterans of working age with children. The exclusion of older Veterans is important to note, given that older adults are one of the fastest growing populations, and Veterans represent a significant proportion of this ageing population. Older adults and particularly older Veterans may experience additional financial barriers that may influence food intake such as limited income due to retirement or an inability to work caused by one or more chronic health conditions; thus, the results cannot be generalised to the Veteran population as a whole. Therefore, the objective of this study was to utilise NHANES to determine predictors of the association between being a Veteran and adult food security, as well as to examine the relation of potential covariates to this relationship.The National Health and Nutrition Examination Survey (NHANES), a programme of studies comprised of questionnaires and physical clinical examinations used to assess the health of a national representative sample of Americans, is another source of potential data to examine this relationship. A recent NHANES study examined the risk for low and very low food security between socio-economically matched Veterans and non-Veterans and found that the prevalence was similar between groups (17·4 % Veterans and 16·7 % non-Veterans) and that Veteran status did not increase the odds of food insecurity in unadjusted or adjusted  analyseswww.cdc.gov/nchs/nhanes/index.htm. Specific to this study, we included only those self-reporting either ‘yes’ or ‘no’ as to whether they had ‘ever served on active duty in the US Armed Forces, military Reserves, or National Guard’. Those answering ‘yes’ were classified as Veterans, and those answering ‘no’ were classified as non-Veterans. During the household interview, adults responded to the ten questions of the US Food Security Survey Module (US FSSM) , race/ethnicity, sex  and education. Race/ethnicities were categorised as the following: Hispanic (Mexicans and non-Mexican Hispanics), non-Hispanic Asian, non-Hispanic Black, non-Hispanic White and ‘Other’ race . Education was categorised as the following self-reported categories: (1) less than high school graduate, (2) high school graduate/GED or equivalent, (3) some college or associates degree or (4) college graduate. If non-Veterans were unable to be matched for all matching criteria to Veterans, these non-Veterans were excluded from the analyses. We were unable to match 22 Veterans 1:2 with non-Veterans for all matching criteria; therefore, these Veterans were matched 1:1 with non-Veterans, resulting in inclusion of 1227 Veterans and 2432 Non-Veterans.2. Diabetes was classified from variables of self-reported history of use of insulin or ‘diabetic pills to lower blood sugar’, and previous diagnosis of diabetes or a measured HbA1c ≥ 6·5 %. CVD was classified from a self-reported history of angina, CHD, myocardial infarction or stroke. Depression was classified based upon participant answers to a nine-item depression screening instrument, which included questions related to: having little interest in doing things, feeling down, trouble sleeping or too much sleep, feeling tired or having little energy, loss of appetite or overeating, feeling bad about oneself, trouble concentrating, moving or speaking slowly or too fast and feelings of being better off dead. Response categories of ‘not at all’, ‘several days’, ‘more than half the days’ and ‘nearly every day’ were given a point ranging from 0 to 3, respectively. Scores for each question were added, and those with aggregate scores ≥ 10 were classified as depressed.The prevalence of several chronic conditions was explored. The BMI variable was used to classify obesity using a cut point of ≥ 30 kg/mHealthcare utilisation, access to care and poverty risk data also were examined. Healthcare utilisation was categorised as the number of self-reported visits  an individual had ‘seen a doctor or other healthcare professional about their health at a doctor’s office, a clinic or some other place’  in the past 12 months. To examine poverty risk, we utilised the ratio of family income to poverty variable to categorise those having scores < 5 as ‘low income’ (income close to or at poverty level) and those with scores of 5+ as ‘high income’ (income at least five times greater than poverty level).P values, one at a time, until all independent variables in the model had a P value less than 0·2. Covariates were selected a prior due to prior literature suggesting their influence on food security–15. Covariates under consideration include age, sex, race/ethnicity, education, ratio of family income to poverty, healthcare utilisation, overnight stay in a hospital, obesity, diabetes, hypertension, CVD and depression. Age was analysed as a continuous variable, but all other covariates were analysed as categorical variables as outlined above and in Table P values were reported.Preliminary data cleaning was performed in R (R version 4.0.4), while all weighted data exploration and analysis were performed in SAS university (9.04.01M6P11072018). Survey means were obtained for continuous variables, while survey frequencies were used for all categorical variables. Survey logistic regression was used in determining predictors of the association between being a Veteran and adult food security, as well as to examine the relation of potential covariates (factors that modify the relationship) to this relationship. The model for the logistic regression was built beginning with a full model including all covariates. A backward stepwise approach was used in determining a best model by removing the covariates with the highest P < 0·001). Regarding chronic conditions, Veterans were more likely to have obesity (44 % v. 38 %), diabetes (20 % v. 16 %) and CVD (16 % v. 10 %) , respectively, but had similar rates of depression as non-Veterans (6 %). Veterans also were more likely than non-Veterans to self-report utilising health care and having a prior overnight hospital stay in the last year . The prevalence of reporting a ‘low income’ was similar between groups (∼79 %).Demographic characteristics between Veterans and non-Veterans are described in Table v. non-Veteran: 79 % v. 80 %), marginal (9 % v. 8 %), low (5 % v. 6 %) and very low (8 % v. 6 %) food security was similar between groups (P = 0·11). Additionally, the questions analysed from the US FSSM revealed similar results with regard to all ten questions , (2) purchasing food that did not last, and not having money to get more  and (3) an inability to afford balanced meals . In those who were asked the remaining seven questions (4–10) due to selecting an affirmative response to the prior three questions, responses related to whether money influenced the following eating pattern decision also did not differ between groups: (4) had to cut size or skip meals , (5) ate less than should , (6) hungry but did not eat , (7) lost weight due to lack of money for food (16 % v. 14 %. P = 0·26) and (8) did not eat for a whole day . Additionally, there was no significant difference in how often adults (9) cut the size of meals or skip meals (79 % v. 79 % P = 0·92) or (10) did not eat for a day .Regarding food security status, the proportion of Veterans and non-Veterans reporting high , P = 0·07). We also found a significant relationship between several of our predetermined covariates and food security status. Non-Hispanic Black , P < 0·001) and other races including multiracial , P = 0·01) were less likely to have high food security compared with non-Hispanic White individuals. Completion of education less than a high school degree , P < 0·001), high school graduate or GED degree , P < 0·001) or some college or associates degree , P < 0·001) were less likely to have high food security compared with college graduates. Individuals with depression were less likely to have high food security compared with those not reporting depression , P < 0·001). Those with high income were more likely to have high food security compared to those with low income , P < 0·001). Additionally, the odds of having high food security increased for each year of age , P < 0·001). No other covariates were found to be significantly associated with food security status  after controlling for a priori factors  when presented overall and when stratified by sex, ethnicity and education are described in Table P = 0·06). Further, we found that non-Hispanic White Veterans were significantly less likely to experience high food security compared with non-Veterans in adjusted analyses , P = 0·02). Similar results were found when examining education where Veterans completing some college, but not having graduated college, were less likely to experience high food security compared with non-Veterans in adjusted analyses , P < 0·05). The risk of food insecurity  did not differ by Veteran status when adjusted for covariates and stratified by any other category of race/ethnicity, education or sex.The odds of Veterans having high food security  was 21 % in Veterans participating in NHANES, which was comparable to non-Veterans (20 %). These results are similar to a prior study utilising NHANES data, but these prior analyses were limited to Veterans with children. Further, they found no significant association in food insecurity between Veterans with children and non-Veterans with children. This contrasts with our current findings and previous findings, including only adults by others reporting that, after adjusting for unknown covariates, Veterans are at greater risk to live in food insecure households compared with non-Veterans. Overall, our study supports prior findings that ethnicity/race, education, income, age and depression are important covariates,15,21.With Veterans often being of poorer health than non-Veterans,21. On the other hand, for Veterans, food security status and racial disparities may not follow this same pattern. After controlling for covariates, we found that non-Hispanic White Veterans were significantly less likely to experience high food security compared with non-Hispanic White non-Veterans. This could be attributed to several underlying factors, including that non-Hispanic White males make up 78 % of the Veterans population and are less likely to have a high school diploma when compared with other Veteran race/ethnicities and their non-Veteran counterparts Additionally, Veterans with or without a high school diploma are more likely to be disabled compared with similar non-Veterans. Therefore, being at increased risk for less education and more disabilities could potentially lower income and may place non-Hispanic White Male Veterans at a greater risk for food insecurity, compared with non-Veterans. It should be mentioned that a high school diploma/GED is a current requirement to enlist in the military; however, this educational requirement has not always been the case. Previous reports suggest that 15 % of Veterans aged 55– 64 years, 24 % aged 65–74 years and 49 % aged 75 years and older did not have a high school diploma upon enlistment, which can be attributed to the military draft between 1940 until 1973 (during peacetime and periods of conflict) when military service was obligatory. These data likely account for the lower education classification within the Veteran cohort. Thus, food security comparison data should be interpreted with the above underlying factors in mind.Our study identified several racial and ethnic groups  as being less likely to have high food security compared with non-Hispanic White individuals, further adding to the evidence that racially and ethnically minoritised individuals are at increased risk for food insecurity within the general population–27. For racially and ethnically minoritised individuals from disadvantaged backgrounds, military service has been shown to improve occupational skills, expand social network,25,27,28 and provide educational financial assistance from the G.I. Bill, which potentially lowers the risk for food insecurity, compared with similar non-Veterans. Other studies have identified additional Veteran specific socio-economic risk factors that increase the risk of food insecurity. This includes a 2021 USDA report on food insecurity among working-age Veterans, which identified those who are younger, have a serious mental illness or recently discharged from active duty, as having a food insecurity prevalence rate that is more than double that of non-Veterans. The identification of socio-economic risk factors specific to the Veteran population is important because it allows for monitoring of those at higher risk and potential interventions on modifiable risk factors.In contrast, military service can increase educational attainment and income for historically excluded groups when compared with similar non-Veterans,30. Varying results are reported between studies that compare prevalence between Veterans and non-Veterans, with studies reporting the prevalence of food insecurity in Veterans to be more, less,11 and comparable  to non-Veterans. Further, methodological differences between studies limit our ability to directly compare our results with those of other studies. One important difference includes how food security status is defined.Studies examining the prevalence of food insecurity among Veterans are inconsistent, with results ranging from 6 % to 25 %,14. Additionally, some define food security status based only on very low food security compared with the combination of high, marginal and low food security, while some simply define food security status based on a ‘yes’ response to one question,31,32. Classifying marginal food security  in the same category as high food security has the potential to underestimate the prevalence and impact of adverse health outcomes associated with exposure to not consistently having access to adequate food. Accumulating evidence suggests that adults with marginal food security are at increased risk for developing a chronic disease , more likely to report poor health, have multiple chronic diseases and at greater risk of impaired nutrition compared with food secure adults. Furthermore, from a public health perspective, categorising marginal food security as food secure limits the ability of policymakers to assess the effectiveness of nutrition assistance programmes in reducing and preventing food deprivation. Therefore, marginal food security was included as a risk indicator for food insecurity in this study. Thus, adult household food security status was defined as high food security v. food insecurity .The criteria used to define food security status are key when interpreting and comparing results as the definition alone could skew the results. Food security status classification schemes vary across studies, with many defining food security status based on a continuum of high, marginal, low and very low food security. Numerous studies that use this continuum, including the US government, classify ‘food secure’ as high and marginal food security and ‘food insecure’ as low and very low food security. A recent review by Cypel et al. reported that twenty out of twenty-one articles examining food insecurities among Veterans used different data sources  surveys, focus groups and pilot studies), baseline characteristics and terminology to define ‘food insecurity’. The design structure of both nationwide population and Veteran Affairs (VA)-based surveys are fundamentally limited in their ability to fully capture or represent the entire US Veteran population. Nationwide population-based surveys, structured to sample civilian populations, often have an imbalance of Veteran to non-Veterans represented, and the Veterans captured may not fully represent the Veteran population  as a whole. As evident by Miller et al., who used data from the Current Population Survey, only 6·5 % of the sample in the published report consisted of Veterans who served post-Vietnam. On the other hand, VA surveys only include Veterans who receive care through VHA. With only 50 % of Veterans receiving care from the VHA, these surveys may not be representative of the entire Veterans population. Additionally, sample populations/baseline characteristics across studies vary from Veterans v. non-Veterans, Iraq and Afghanistan Veterans, Women Veterans, Minneapolis Veterans, Veterans with HIV, Veterans with children, etc., with target populations ranging from 18 to 85 years of age. Covariates also tend to differ across most studies,30–32. Like our study, many controlled for age, sex, race/ethnicity, education, depression and income,11,31. Other covariates used in studies include, but are not limited to, the presence of immigrants in the home, marital and employment status, tobacco and alcohol use, military rank, trauma exposure and various health conditions,30–32. With no standardised methodology established to examine food insecurity in Veterans, our ability to generalise and interpret results between studies is limited.In addition to the various classification schemes, studies examining food security status in Veterans use a wide variation of surveys, sample populations and covariates. This workgroup has partnered with government and non-profit organisations to: examine food insecurity issues, identify Veterans at risk, promote interprofessional care and support the expansion of VA facilities involved in on-site or mobile food panties (Veterans Pantry Pilot), which currently serve more than 40 000 Veterans at seventeen VA locations. Additionally, in 2017, the VHA implemented a one question food insecurity screener, which is completed on all non-institutionalised Veterans receiving care. The integration of the food insecurity screener is a critical step to identify and provide assistance to vulnerable Veterans. As of 2020, over 5 million Veterans have been screened.Due to the availability of NHANES data, our results are limited to the time frame of 2011–2016. The evaluation of affirmative responses to the first three independent questions of the US FSSM found ∼20 % of Veterans reported worrying about food running out, not having enough money to get more food and affording balanced meals. Additionally, of these food insecure Veterans, over 40 % reported that they had to cut the size or skip meals and/or eat less than they felt they should have because there was not enough money to buy food. Furthermore, though the prevalence of affirmative responses to the question about not eating for a day because there was not enough money for food did not differ statically between food insecure Veterans (85 %) and non-Veterans (77 %), these results should be interpreted in light of the small sample of respondents for this question (only 33 Veterans and 77 non-Veterans) and in regard to their clinical relevance. These results are alarming and intensify the need for access to resources available to alleviate food insecurity in Veterans. However, it must be noted that efforts to improve food security status in Veterans are constantly evolving. As a result of a 2015 Congressional briefing on Veteran food security, the VHA formed ‘The Ensuring Veteran Food Security Workgroup’ to address this issue. However, many individuals may not be utilising these resources and programmes. For example, 59 % of eligible Veterans do not participate in the SNAP. Several barriers may limit Veteran participation, including lack of knowledge of available resources, stigma surrounding programme utilisation, pride and beliefs about self-reliance that may have developed during military service. Additionally, many may be ineligible for federal nutrition programmes based on income limits. The State of Hunger in American 2016 reported that two-thirds of food insecure older adults have income over the federal poverty line, thus not qualifying for SNAP. This scenario could also affect some food insecure Veterans; however, that has yet to be determined.In addition to VA programmes and initiatives, both federal ) and community (i.e. food panties) resources are available to food insecure Veteransv. urban community location) that may modify the relationship between Veteran status and food security could not be explored. This is an area for future studies to explore. Additionally, the analyses include both fixed and modifiable covariates and do not allow for determination of temporal direction of the effect, rather they only allow for determination of an association between the variables of interest. Furthermore, Veterans NHANES is a nationwide general population survey that does not seek to sample Veterans. Thus, selection bias may have resulted in an imbalance of Veteran to non-Veterans and may not fully represent the entire Veteran population. However, the large number of non-Veterans represented allowed us to closely match Veterans to non-Veterans. Finally, the small sample size of the food security comparison data (see Table There are several limitations to the current study. First, the cross-sectional study design and self-report response bias prevent any conclusion from being drawn about cause and effect and how the prevalence of food security may change over time. Due to limitations in data collected by NHANES, other potential covariates (i.e. combat exposure, service era, occupation during military service and rural In order to develop interventions better suited to address the unique needs of the Veteran population, it is essential to understand the risk and the socio-economic factors associated with food security status in Veterans compared with non-Veterans. After adjusting for covariates, we found that Veterans are less likely to experience high food security compared with non-Veterans. This study supports previous research that identified ethnicity and/or race, education, income, age and depression as important covariates when examining food security status in the Veteran population. Additionally, it adds to the literature by highlighting ethnicity and level of education as important socio-economic determinates of food security status in Veterans.


Bladder cancer (BCa) is the 10th most common type of cancer worldwide, and human papillomavirus (HPV) is the most common sexually transmitted infection. However, the relationship between HPV infection and the risk of BCa is still controversial and inconclusive.This systematic review and meta‐analysis were conducted following the PRISMA 2020 reporting guideline. This study searched four bibliographic databases with no language limitation. The databases included PubMed (Medline), EMBASE, Cochrane Library, and Web of Science. Studies evaluating the interaction between HPV infection and the risk of BCa from inception through May 21, 2022, were identified and used in this study. This study estimated the overall and type‐specific HPV prevalence and 95% confidence intervals (95% CI) using Random Effects models and Fixed Effects models. In addition, this study also calculated the pooled odds ratio and pooled risk ratio with 95% CI to assess the effect of HPV infection on the risk and prognosis of bladder cancer. Two‐sample mendelian randomization (MR) study using genetic variants associated with HPV E7 protein as instrumental variables were also conducted.p = 0.0011; HPV 18 E7 protein: IVW OR per unit increase in protein level = 1.0003 [95% CI: 1.0001–1.0005]; p = 0.0089).This study retrieved 80 articles from the four bibliographic databases. Of the total, 27 were case–control studies, and 53 were cross‐sectional studies. The results showed that the prevalence of HPV was 16% (95% CI: 11%–21%) among the BCa patients, most of which were HPV‐16 (5.99% [95% CI: 3.03%–9.69%]) and HPV‐18 (3.68% [95% CI: 1.72%–6.16%]) subtypes. However, the study found that the prevalence varied by region, detection method, BCa histological type, and sample source. A significantly increased risk of BCa was shown for the positivity of overall HPV , which was also influenced by study region, detection method, histological type, and sample source. In addition, the study found that HPV infection was significantly associated with the progression of BCa . The two‐sample MR analysis found that both HPV 16 and 18 E7 protein exposure increased the risk of BCa (HPV 16 E7 protein: IVW OR per unit increase in protein level = 1.0004 [95% CI: 1.0002–1.0006]; In conclusion, HPV may play a role in bladder carcinogenesis and contribute to a worse prognosis for patients with BCa. Therefore, it is necessary for people, especially men, to get vaccinated for HPV vaccination to prevent bladder cancer. Studies have found that HPV is the most common sexually transmitted infection among humans.The urinary tract is anatomically close to the genital tract. As a result, HPV has a high probability of infecting the urinary epithelium of the bladder.Mendelian randomization (MR) is a method that uses genetic variants as instrumental variables of the exposure to evaluate the causal effects of the exposure on an outcome to exclude the influence of the confounding factors inherent in observational studies.22.1The inclusion and exclusion criteria were as follows: (1) The exposure of interest was HPV infection in bladder tissues; (2) The outcome of interest was bladder cancer; (3) This study only included the latest patient datasets reported in different articles; (4) Immunosuppressed patients such as those accepting organ transplant or with immunodeficiency were excluded; (5) Patients with secondary malignant tumors of the bladder and cervical lesions simultaneously were excluded; (6) Studies using cell or animal models and case reports were excluded; (7) Studies without full text or lack of valuable data were excluded. The search was not limited to any language or publication status.2.2This study was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta‐analyses (PRISMA) 2020 reporting guideline.2.3This study used a designed data extraction sheet to extract information from the included studies. The data extraction sheet consisted of bibliographic information and background information. Bibliographic information had author's name, year of publication, journal name, and title. Background information included the country where the study was carried out, the inclusion and exclusion criteria for patients, age, percentage of male patients, and the smoking rate of the patients. In addition, background information had sample source, detection method, types of HPV detected, histological types of bladder cancer, the prevalence of HPV  in bladder tissues, matching criteria if the study design was case–control and follow‐up duration, and the outcome of patients. Moreover, if the prevalence of HPV was detected using two or more methods, such as polymerase chain reaction (PCR) and in situ hybridization (ISH), the results of PCR were used for further analyses. The detailed characteristics of the articles included in this study are shown in Table 2.4The evaluation criteria for an observational study of the Agency for Healthcare Research and Quality (AHRQ) were adapted to evaluate the quality of cross‐sectional studies.2.5χ2 (Cochrane's Q) test with a significance level of α = 0.10 and the I2 test.I2 describes the percentage of variation across studies, and an I2 statistic value of ≥50% indicates considerable heterogeneity.p < 0.05 was considered significantly different.This study estimated the prevalence of overall and type‐specific HPV and 95% CI using the size and number of HPV‐positive infections in BCa patients using Random Effects (RE) models or Fixed Effects (FE) models.2.6https://gwas.mrcieu.ac.uk/; version: v6.5.2‐2022‐04‐11), developed at the MRC Integrative Epidemiology Unit at the University of Bristol.The data resources were obtained from MRC IEU OpenGWAS . Five MR methods were used: Weighed median regression, Inverse variance weighting (IVW), Mendelian randomization‐Egger (MR Egger), Simple mode, and Weighed mode. The IVW method with RE was the main statistical model. This study applied the SNP‐specific Wald ratio to evaluate the causality. The pleiotropy test tested the pleiotropic effects, and p ˃ 0.05 was regarded as having no pleiotropic effects. Heterogeneity was tested using the Cochrane Q value. Supporting Information: Tables Supporting Information: Table p values were two‐tailed, and the R software (version 4.2.0) with the Two Sample MR packageAll 3This study retrieved 546 publications from electronic databases and other sources. However, after applying the inclusion and exclusion criteria in Figure 3.1The characteristics of the 80 articles included in this study are shown in Table In these studies, most patients were more than 60 years, and the percentage of male patients was greater than 80%. It was found that only one study focused on female patients with BCa.3.2This study adopted the Agency for Healthcare Research and Quality (AHRQ) evaluation criteria to evaluate the quality of cross‐sectional studies, as shown in Supporting Information: Table 3.3I2 = 96%, RE model), as shown in Figure The 80 studies had 6065 patients with BCa, in which the prevalence of HPV ranged from 0% to 100%, and the overall HPV prevalence was 16% . However, Begg's test did not show a significant publication bias .A contour‐enhanced funnel plot was constructed because the results found that the articles included in this study had significant heterogeneity. However, the result in Supporting Information: Figure p = 0.2153) and the smoking rate (p = 0.8540), as shown in Supporting Information: Table Besides, meta‐regression was also performed to find out the latent confounding variables. The study used the percentage of male patients and the smoking rate to construct the univariate meta‐regression model, as shown in Supporting Information: Figure 3.4I2 = 60%, RE model). A subgroup analysis stratified by continent, detection method, histological subtype, and sample source was also performed, as shown in Figure A total of 25 case–control studies comprising 1621 BCa patients and 685 used were included to investigate the association between HPV infection and the risk of BCa. Two of these studiesz = −0.66, p = 0.5091) and Egger's test . In addition, the cumulative meta‐analysis and sensitivity analysis were performed by stepwise addition and deletion of studies. There were no observable changes in the POR, as shown in Supporting Information: Figures A funnel plot shown in Supporting Information: Figure p = 0.0078) and might serve as a latent confounding factor. On the other hand, the models constructed based on age (p = 0.5547), smoking rate (p = 0.5918) and the publication year (p = 0.3295) had no statistical significance, as shown in Supporting Information: Table In univariate meta‐regression, the study found that the percentage of male patients was significantly associated with the increased risk of BCa   and Egger's test .The funnel plot did not show good symmetry, as shown in Supporting Information: Figure p = 0.0326), while the models constructed based on follow up duration (p = 0.3950), publication year (p = 0.6786), age (p = 0.4156), the percentage of male patients (p = 0.8388), smoking rate (p = 0.0867) and HPV‐16 prevalence (p = 0.5226) all lacked statistical significance, as shown in Figure In univariate meta‐regression, the study found the prevalence of HPV‐18 was negatively associated with the risk of BCa (3.6p = 0.7473), as shown in Supporting Information: Table The data source for this two‐sample MR study was shown in Supporting Information: Table p = 0.0011; HPV 18 E7 protein: IVW OR per unit increase in protein level = 1.0003 [95% CI: 1.0001–1.0005], p = 0.0089).The study also performed the leave‐one‐out analysis to exclude the influence of individual SNPs on the overall causal estimate by the stepwise removal of each SNP and repeating the MR analyses. The leave‐one‐out analysis showed a relatively stable outcome after removing each SNP, as shown in Figure 4An early meta‐analysis published in 2011p = 0.0011; HPV‐18 E7 protein: IVW OR per unit increase in protein level = 1.0003, p = 0.0089), implying that this interaction represents a causal effect of HPV infection.A total of 6065 BCa cases were included in this study, in which the prevalence of HPV ranged from 0% to 100%, yielding a pooled HPV prevalence of 16% (95% CI: 11%–21%), consistent with the previous meta‐analysis.BCa is the 10th most common cancer worldwide with high morbidity and mortality rates. Smoking and exposure to several chemicals are known risk factors for BCa and it is important to identify the latent risk factors to prevent BCa. HPV is a family of sexually transmitted DNA‐based viruses that infect the stratified squamous epithelia, and more than 150 HPV subtypes have been identified,p = 0.8540). Differences in these outcomes are because: First, smoking status was not accurate in some studies because of information bias, and the duration as well as smoking dose were unknown in most studies, which was significantly associated with HPV prevalence. Second, most of the included patients were male, however, HPV prevalence was higher among female smokers. Finally, only a limited number of studies reported on the smoking status of patients, therefore, the result should be interpreted with caution.Smoking is an acknowledged risk factor for bladder cancer and has been highly associated with higher incidences of HPV infection , which was dose‐dependent and more significant for female patients  and high‐risk HPV subtypes.Globally, HPV infections account for 630 000 new cancer cases per year, among which 83% are cervical cancer cases.HPV‐associated oropharyngeal squamous cell carcinoma (OPSCC) was associated with worse overall survival outcomes, relative to non‐HPV‐associated OPSCC, even after adjusting for smoking status.Then, we investigated the causal relationship between HPV E7 protein levels and BCa risk. The meta‐analysis for different bladder cancer datasets showed that genetically elevated HPV E7 levels are causally associated with increased BCa risk for both HPV‐16 and HPV‐18, consistent with the findings from previous meta‐analyses of conventional observational studies after exclusion of latent bias caused by confounding factors. Although statistically significant, the OR values for HPV‐16 and HPV‐18 E7 proteins on BCa were close to 1 and dependent on E7 protein levels, therefore, this result should be carefully interpreted. Besides, clinical assessment of E7 protein levels is difficult and lacks practical significance. Apart from these limitations, findings from two‐sample MR analysis are in accordance with the result of this systematic review and meta‐analysisSchistosoma hematobium infections, which could probably influence the outcomes of this study. Third, we only found a dataset for HPV E7 protein levels but did not find other instrumental variables for HPV infections. Fourth, there was a great heterogeneity in the characteristics of the study cohort. Fifth, detection methods for some studies were not sensitive enough and did not detect the specific HPV subtypes, which may have interfered with the final outcome. Finally, there were various limitations regarding our analysis of HPV and BCa progression. The number of studies included in this section was limited. Recurrence and death were not valid outcomes for prognosis, especially when the causes of death were not confirmed and specified and when the HPV persistence/clearance was unknown during BCa treatment/follow‐up. Several potential confounders during prognosis were unknown and were not controlled for in the analysis. Therefore, functional studies using cell lines and animals as well as clinical studies should be performed to confirm our findings.This study has various limitations. First, due to the lack of original data, we did not investigate the role of HPV infection in different stages of bladder cancer. Second, most SCC cases were associated with 5HPV infection is significantly associated with increased risk and worse prognosis of bladder cancer. Therefore, HPV vaccination is necessary to prevent bladder cancer, especially among men. Future studies should investigate the association between HPV infection and bladder cancer using large‐scale sampling of various populations. Moreover, the mechanisms behind these phenomena should be elucidated.Jian‐Xuan Sun, Jin‐Zhou Xu, Chen‐Qian Liu, Qi‐Dong Xia, and Shao‐Gang Wang contributed to developing the main research question, carrying out the literature search, collecting the included studies’ information, and describing the results. Jian‐Xuan Sun, Jin‐Zhou Xu, and Chen‐Qian Liu performed the meta‐analysis and wrote the first draft of the manuscript. Xing‐Yu Zhong, Na Zeng, Hao‐Dong He, and Si‐Yang Ma contributed to developing the main research question and revised the manuscript. Ye An, Meng‐Yao Xu, Zheng Liu, and Jia Hu revised the manuscript. All authors contributed to the article and approved the submitted version. Jian‐Xuan Sun, Jin‐Zhou Xu, Chen‐Qian Liu, Qi‐Dong Xia, and Shao‐Gang Wang contributed equally to this study.The authors declare no conflict of interest.Supporting information.Click here for additional data file.Supporting information.Click here for additional data file.Supporting information.Click here for additional data file.Supporting information.Click here for additional data file.Supporting information.Click here for additional data file.Supporting information.Click here for additional data file.Supporting information.Click here for additional data file.Supporting information.Click here for additional data file.Supporting information.Click here for additional data file.Supporting information.Click here for additional data file.Supporting information.Click here for additional data file.Supporting information.Click here for additional data file.Supporting information.Click here for additional data file.Supporting information.Click here for additional data file.Supporting information.Click here for additional data file.Supporting information.Click here for additional data file.Supporting information.Click here for additional data file.Supporting information.Click here for additional data file.Supporting information.Click here for additional data file.Supporting information.Click here for additional data file.Supporting information.Click here for additional data file.Supporting information.Click here for additional data file.


Adverse childhood experiences (ACEs) and exposure to potentially traumatic events (PTEs) during military service are associated with mental health problems. However, knowledge about relative contributions of these factors to non-U.S women combat veterans’ posttraumatic sequalae is sparse.To examine associations between ACEs, combat exposure, military sexual trauma (MST), potentially morally injurious events (PMIEs), posttraumatic stress disorder (PTSD) and complex PTSD symptoms among women veterans.n=885) and non-combat veterans (n=728) responded to self-report questionnaires in a cross-sectional design study.A volunteer sample of Israeli women combat veterans (Combat veterans reported more total average ACEs, were more likely to experience 3 or more ACEs and specific ACEs of physical abuse and emotional neglect, as compared to non-combat veterans. Combat veterans also reported higher levels of combat exposure, PMIEs, higher prevalence of MST and higher levels of PTSD symptoms, but not CPTSD symptoms, as compared to non-combat veterans. Importantly, ACEs, combat exposure, MST-assault and PMIEs of betrayal predicted PTSD symptoms, while only ACEs and PMIEs of betrayal predicted complex PTSD symptoms.This study emphasized the relatively high exposure to PTEs and PTSD symptoms of women combat veterans as compared to non-combat veterans. Our findings also confirm prior studies demonstrating associations between ACEs, combat exposure, MST and mental health problems. Importantly, we demonstrated the unique contribution of betrayal based PMIEs and the differential associations of PTEs with PTSD and Complex PTSD symptoms among combat veterans.None Declared


Objective and Participants: The authors sought an updated examination of attitudes toward Human Papillomavirus (HPV) catch-up vaccination among college students at a private religious university. Methods: A total of 1557 college students completed a 62-question survey of religious and HPV vaccination attitudes during the fall of 2021. Students’ willingness to receive catch-up HPV vaccination and willingness to vaccinate a future child against HPV were recorded. Results: Of the 46.8% of students who reported being unvaccinated or unaware of vaccination status, ~26% reported being uninterested in receiving catch-up HPV vaccination; ~22% of all students surveyed reported being unwilling to vaccinate a future child against HPV. The strongest predictors of vaccine hesitancy included religious concerns about sexual abstinence and safety concerns. Conclusions: College health professionals can increase the rate of HPV vaccination among college students and subsequent future generations by addressing the safety and utility of the vaccine regardless of intentions for sexual abstinence prior to marriage. Additionally, rather than a uniform approach to all students who self-identify as Christian, an effort to identify and discuss the unique religiously influenced beliefs of individual students is recommended when discussing HPV vaccination. An estimated 43 million Americans are currently infected with Human Papillomavirus (HPV). With 13 million new cases expected annually, HPV is the most common sexually transmitted infection in the United States ,3,4.Among the 40 different HPV strains that are sexually transmitted, low-risk HPV types cause transient infections, such as genital skin warts. High-risk HPV infections can persist in lesions that may progress to cancers of the oral cavity, oropharynx, vulva, vagina, cervix, penis, or anus ,6. OncogGardasil-9 is an FDA-approved vaccine that protects against 9 strains of HPV, including types 16 and 18. A complete HPV vaccination series prevents nearly 100% of HPV-associated cancers in males and females ,13. The Despite the clear benefit, HPV vaccination rates in the United States fall far below the Healthy People 2020 goal of 80%. As of 2019, only ~54% of adolescent girls and boys aged 13 to 17 were estimated to have completed the HPV vaccine series . SimilarMultiple reasons for parental non-adherence to the ACIP’s recommendation for HPV vaccination have been explored, including a lack of HPV and vaccine awareness, lack of provider recommendation, parental safety concerns, and concerns over perceived link to increased sexual activity ,21,22,23While multiple studies have attempted to examine the reasons students arrive at college campuses unvaccinated, less attention has been given to robust examination of religious college student attitudes toward HPV “catch-up” vaccination . Even after the need for catch-up vaccination is noted, studies suggest that vaccine uptake among college students is minimal ,31,32. AA limited number of recent studies have suggested barriers to catch-up vaccination among college students, including fear of negative health consequences, perceived social influences, and fewer provider recommendations ,36,37,38The goal of this study was to address these gaps in the published literature regarding religious college student attitudes toward the HPV vaccine with a focus on relationships between vaccination attitudes and specific religious beliefs and traditions. We aimed to characterize factors that influence willingness to receive catch-up HPV vaccination among students at a major Christian university. Then, based on the assumption that these college students are likely to become parents, healthcare providers, or community leaders, we further sought to characterize factors underlying resistance to vaccination of current or future children, specifically focusing on religiously influenced views regarding sexuality. Our results suggest that college health professionals and educators may play an influential role in promoting the HPV vaccine among college students by addressing common misconceptions about the vaccine, particularly among students struggling to reconcile religious values with perceived controversial healthcare decisions. The information provided by this study will aid healthcare professionals in discerning the best strategies for HPV vaccine promotion on college campuses, particularly on college campuses with a large proportion of religious students. However, a “one-size-fits-all-Christians” approach is not supported by our data; rather, health promotions should honor the variability in beliefs and attitudes among Christian students.This cross-sectional study of vaccination attitudes was conducted from August to December 2021 among a convenience sample of college students at Baylor University, a private Baptist university in central Texas that enrolls a high proportion of religious students. A convenience sample was utilized due to logistical barriers to random sampling. The self-administered survey was approved by Baylor University’s Institutional Review Board and delivered using Qualtrics XM . Subject recruitment occurred through posted fliers and announcements by professors at Baylor University during the fall semester of 2021. To incentivize participation, professors offered extra credit in their courses for student participation. Faculty who advertised the survey were recruited through two methods: (1) contacting professors whom the undergraduate researchers knew and had a relationship with and (2) emailing professors of high undergraduate enrollment courses. Involved professors ranged in discipline from biology to business to philosophy. In most cases, the recruitment process occurred early in the semester, prior to when professors may have developed the trust relationship required to influence student responses on the survey regarding vaccination. Further, students were assured that the survey responses would be confidential to avoid response bias.In addition to collecting demographic information, students were asked about their HPV vaccination status using the prompt “I have initiated or completed the HPV vaccine series.” The response options were “Yes, I have been vaccinated against HPV”, “No, I have not been vaccinated against HPV”, or “I do not know whether I have been vaccinated against HPV.” Students were also asked about openness to receiving the vaccine using the following question and response options: “The HPV vaccine is recommended for individuals under the age of 26. If you are unvaccinated  and within this age range, would you agree to consider receiving the vaccine? You will not be contacted about receiving the vaccine if you answer yes” with response options: “Yes, I would consider receiving the HPV vaccine,” “I am not in this age range but I would consider getting the vaccine if I were,” “No, I would not consider receiving the HPV vaccine,” “I am not in this age range but would not consider the vaccine if I were,” or “I have already received the HPV vaccine.”“This question wants to know if you agree that the moon is located in outer space. Please choose the answer that says, ‘neither agree nor disagree’”) served to ensure attentive survey completion. Individuals who failed the attention checks were removed from the final survey population. The survey was open for four months, and in total, 1557 valid responses were collected from undergraduate students at Baylor.Respondents were also asked about personal religious beliefs and affiliations, opinions about vaccine safety, knowledge of HPV, HPV transmission, and the HPV vaccine. Where appropriate, responses were collected on a 5-point Likert scale. Individuals who did not progress through the entire survey, individuals under the age of 18, and individuals who were not undergraduate students at Baylor were removed from the data pool. Respondents were given the option to elect against answering questions due to the uncomfortable nature of the subject, and blank responses were replaced with the question’s average Likert response value during data analysis. Throughout the survey, various attention check questions  and Catch-up Vaccine Resistant . The intent to vaccinate future children against HPV was assessed using the following prompt: “I am likely to vaccinate my children against HPV OR I have vaccinated my children against HPV.” This outcome measure was divided into “Vaccine Accepting” (including students who answered Strongly Agree or Agree) and “Vaccine Hesitant” .The primary outcome variables assessed were the students’ reported openness to vaccinate themselves (a measure of their attitude toward catch-up vaccination) and intent to vaccinate future children against HPV. Among unvaccinated students and students unaware of their vaccine status, attitudes toward catch-up vaccination were dichotomized into two responses: Catch-up Vaccine Accepting . Specifically, a table containing the responses to all questions across all participants was used as input to the random forest analysis. The Likert scale response data for the target question was then transformed into one of two categories based on whether the response was positive or negative. The data used to train the machine learning model consisted of a randomly selected 70% of participants, while responses from the remaining 30% of participants were then used to test the model. The number of trees generated in the random forest for the target question was 10,000, while the number of variables randomly sampled as candidates at each split was ~8, equal to the square root of the number of columns present in the input table. The mean decrease in Gini index values, which represents entropy/impurity of a feature/question, with larger values representing more features/questions that were most useful in classifying the data, were calculated for each feature/question in the input table. The output from this analysis consisted of a table with the quantitative data for each question on a separate row. All responses were 93.97% accurate at predicting responses to Q42 with an area under the receiver–operator characteristic curve of 97.18%.Random forest analysis was then used to identify survey questions that were most associated with responses to two target questions. This was performed using version 4.7–1.1 of the random forest library within the R statistical software . To follow up on responses that were identified as reliable predictors of vaccination hesitancy in the random forest analyses, student responses to individual questions were compared using Pearson’s Chi-squared test, where The study sample consisted of 1557 responses from Baylor University undergraduate students, including 497 males and 1052 females aged 18–30 (Mean (M) age = 19.2; SD = 1.3; Of the respondents, 53.2% reported having initiated or completed the HPV vaccine series, 21.1% reported not being vaccinated against HPV, and 25.7% were not aware of their vaccination status . Our firStrikingly, strong predictors of openness toward HPV catch-up vaccination were the responses to questions regarding the acceptability of sexual activity prior to marriage and the student’s adherence to religious teachings regarding sexual activity prior to marriage. Similarly, responses to questions regarding the utility of HPV vaccination for sexually abstinent individuals were predictive of stance toward catch-up vaccination, as were responses to questions about the safety of the HPV vaccine. These findings suggest that HPV catch-up vaccination outreach efforts on religious campuses will require efforts to explain the benefit and safety of HPV vaccination even if sexual abstinence is intended.For catch-up intervention purposes, we considered the target audience for vaccination intervention strategies to be those students who did not report previous vaccination against HPV. This target population included students who were knowingly unvaccinated or unaware of their vaccination status. Of the students who did not report previous HPV vaccination, only 73.7% were open to considering HPV vaccination; the remaining 26.3% of the students were resistant to the idea of catch-up vaccination . To deteReligious affiliation and religiously related viewpoints were significantly associated with unwillingness to explore HPV catch-up vaccination . AlthougIn part, resistance to catch-up vaccination among religious students may be linked to the perception that the vaccine contains ingredients that conflict with religious beliefs. Among religious students with this concern, 65.1% were unwilling to consider receiving the vaccine. For a greater number of students, religiously related views regarding premarital sex appear to influence the choice to explore HPV catch-up vaccination. Those students who viewed premarital sex as unacceptable were significantly less open to considering catch-up vaccination in comparison to those who do not hold the same belief. Among religious students who expressed adherence to their religion’s teachings concerning sexual behavior, 34.6% reported hesitancy toward catch-up vaccination. Further, students who agreed or strongly agreed with the statement “People with diseases caused by HPV are responsible for their own suffering, because the virus is only transmitted through promiscuous sexual practices” were significantly less likely to be open to catch-up vaccination.Data analysis further revealed associations between catch-up vaccination hesitancy and misconceptions about the utility of the HPV vaccine for those who abstain from sexual activity prior to marriage. Among the target population for HPV catch-up vaccination, 62.0% of students who agreed with the statement “If an individual abstains from sexual activity before marriage, they do not need to receive the HPV vaccine” were also unwilling to consider receiving the vaccine; by comparison, only 18.0% of students who do not hold this view were vaccination hesitant. Very similar results were obtained in response to the prompt “The HPV vaccine is not necessary if an individual has only one sexual partner in their lifetime.” These viewpoints held by Christian students who were resistant to catch-up vaccination suggest that they do not view themselves as currently at risk of HPV infection nor do they conceive of possible future exposures to HPV. The belief that those who do contract HPV are responsible for their own suffering suggests a reluctance to prevent the consequences of what they may consider sexual sin. Together, these responses illuminate the notion that hesitancy toward catch-up HPV vaccination may be rooted in naivete about the utility of the HPV vaccine despite sexual abstinence before marriage.A lack of awareness about modes of HPV transmission was also noted among the study population, which may contribute to a false sense of safety. Out of all students surveyed, 96.1% of students correctly identified vaginal–penile sex as a mode of HPV transmission, but only 83.0% of students correctly identified oral sex  as a way to contract HPV . AdditioIn addition to concerns regarding the utility of the vaccine among students who do not intend to have multiple sexual partners prior to marriage or more than one sexual partner for life, apprehensions about vaccine safety were also significantly associated with resistance toward the HPV vaccine . A signiBecause parental or guardian choice determines whether children receive the HPV vaccine in the optimum window (ages 11–15), college health educators and professors possess a unique opportunity to influence future generations’ HPV vaccination rates nationwide by advocating for the HPV vaccine among current generations of college students. Design of outreach opportunities require an updated examination of attitudes toward the vaccination of children against HPV in a post-COVID society. For this reason, we also examined the attitudes of all students in the survey, regardless of their own HPV vaccination status, toward vaccination of current or future children. Interestingly, while 96.8% of students surveyed predicted vaccinating their current or future children with basic recommended childhood vaccines, only 77.7% predicted vaccinating children with the HPV vaccine, suggesting that a unique hesitancy toward the HPV vaccine exists.To better characterize the basis for hesitancy toward vaccinating current or future children against HPV, a random forest machine learning model was used to identify which survey questions best predicted student response to the survey question “I am likely to vaccinate my children against HPV OR I have vaccinated my children against HPV.” The results of this random forest analysis are summarized in Our modeling revealed multifactorial reasoning for resistance against vaccination of children against HPV. Similar to catch-up vaccination attitudes, predictive questions involving religious values and concerns regarding sexual behaviors were a striking theme. Other, somewhat less predictive questions addressed generalized vaccine efficacy and safety beliefs, safety and efficacy concerns specifically regarding the HPV vaccine, and other various social factors. Bivariate analyses were used to explore the directionality of the association between responses to questions in the identified categories and the students’ stances toward vaccinating current or future children against HPV.Because the random forest model indicated concerns regarding sexual purity prior to marriage as a strong predictor of negative HPV vaccine attitudes, the following sections pay particular attention to the religious beliefs of this student population. The associations between religious devotion and student attitudes toward vaccinating future children against HPV are shown in We noted that Christians are not uniform in their stance toward vaccination of children against HPV; the proportion of hesitant students of different denominations ranged from 16.4% to 34.2% . ChristiThe nature of HPV as a sexually transmitted infection (STI) is regarded as a barrier to advocating for the HPV vaccine among religious populations. As found in the exploration of catch-up vaccination attitudes, religious beliefs concerning sexual behavior were predictive of negative HPV vaccine attitudes; however, specific misconceptions about the administration of the vaccine or a failure to acknowledge possible future HPV exposure scenarios are important avenues for exploration to guide future intervention campaigns for both catch-up vaccination of young adults and future vaccination of adolescents.As found for catch-up vaccination, the results of random forest analysis indicated that responses to statements regarding sexual monogamy, such as “If an individual abstains from sexual activity prior to marriage, they do not need to receive the HPV vaccine” and “The HPV vaccine is not necessary if an individual only has one sexual partner in life” were strongly associated with HPV vaccination attitude . BivariaIn contrast to deliberating the choice to self-vaccinate against HPV, prior studies have suggested that parental resistance to vaccinating their children is partly rooted in a misconception that vaccination against HPV contributes to earlier onset of sexual activity among adolescents. Random forest and bivariate analyses indicated that this concern was at play in our population as well. Students who agreed with statements such as “Vaccinating children against HPV will make them more likely to have premarital sex” or “The possibility of contracting HPV helps prevent premarital sex” reported a lower intent to vaccinate future children . StrikinIn addition to concerns about the necessity of the HPV vaccine for sexually abstinent individuals, the random forest model further identified concerns over vaccine safety and efficacy to be predictive of HPV vaccination hesitancy with regard to vaccinating future children. The association between concerns about the safety and efficacy of the vaccine and students’ attitudes toward HPV vaccination for future children is shown in Interventions to promote HPV awareness and HPV vaccination among college students can address two purposes: the short-term objective of encouraging catch-up vaccination and the long-term goal of shaping future parents’ stances regarding the vaccination of children against HPV. To guide vaccination campaigns on college campuses, particularly religious campuses where HPV vaccination hesitancy may be heightened, a clear and current view of student perceptions regarding the vaccine is required. In addition to providing a more refined view of Christian college students’ attitudes toward HPV vaccination, this study captures the attitudes of students whose education was dramatically impacted by the effects of the COVID-19 pandemic and COVID-19 vaccination policies. Our findings suggest that in addition to wariness surrounding general vaccine safety, many students possess misconceptions about the HPV vaccine that are related to beliefs about sexual behavior promoted in many Christian households. College health providers and educators are uniquely poised to address these concerns as well as any additional safety and efficacy misconceptions that might have been reinforced by COVID-19 vaccine debates. Importantly, however, practitioners will not be able to apply a uniform approach to all Christian students, nor can efforts be focused on a singular Christian tradition or denomination. Christian students of the same denomination vary in their stance toward the vaccine. Rather, the educator could explore specific beliefs about sexual activity and HPV transmission.Approximately 50% of students surveyed in this study reported having initiated or completed the HPV vaccine series. Approximately one-quarter of the population (25.7%) was not aware of their HPV vaccination status, indicating that young adults have difficulty remembering their vaccination experience, due to its initiation in childhood and adolescence. This lack of knowledge about vaccination status presents a barrier for college healthcare providers, as a student may be unmotivated to pursue the HPV vaccine series if they do not know whether they have previously initiated or completed the series. Therefore, efforts by college healthcare providers to empower young adult students to explore their vaccination history may be particularly fruitful in promoting catch-up vaccinations, increasing the likelihood that an unvaccinated student might seek more information about the HPV vaccine and potentially initiate or re-initiate the vaccine series.Of the 46.8% of students who either reported being unvaccinated or were unaware of their vaccination status, approximately 26.3% were not open to considering catch-up vaccination . ConsistIn particular, students who hold the belief that the HPV vaccine is not necessary if an individual does have sex until marriage are less likely to indicate a willingness to initiate the HPV catch-up vaccine series. Similarly, embracing religious attitudes involving sexual purity is a strong negative predictor of the intent to vaccinate a future child against HPV. Therefore, while educators or healthcare providers for young adults may be mindful and attentive to the concerns of Christian students when promoting the HPV vaccine, they may be able to more quickly uncover sources of resistance to the HPV vaccine if a frank discussion of sexual behavior can be achieved. We assume that the resistance to HPV vaccination (both catch-up vaccination and vaccination of children) is caused, in part, by the belief that sexual contact will be avoided by Christian adolescents due to commitment to religiously motivated abstinence. This assumption is supported by the difference in attitude toward the HPV vaccine versus other childhood vaccinations. Only ~77% of the surveyed population predicted vaccinating with the HPV vaccine while over 96% of students predicted vaccinating future children with the other childhood vaccines.For these reasons, efforts to explain the utility of the HPV vaccine may be more successful if focused on the importance of the HPV vaccine in protecting against multiple types of cancer or unexpected life circumstances, rather than asking a student to part with their devotion to their religious identity. Further, a conversation discussing the modes of transmission of HPV might be required or helpful. Religious adolescents may believe that they preserve “technical virginity” by only having oral sex instead of penile–vaginal sex. Because Christian adolescents are often taught to preserve their virginity until marriage, some believe that they can still participate in oral sex, without committing sexual immorality according to the Bible, and thus remain a “technical virgin.” Among our study population, 17.0% of students reported not knowing that HPV could be spread through oral sex . TherefoTogether, these results suggest that a two-pronged approach to intervention among college students may be effective: (1) discussions about vaccine safety versus HPV-associated cancer risks and (2) carefully encouraging students to consider protecting themselves against unfortunate future events outside their control, such as infidelity or undetected prior HPV infection of their future spouse, could be beneficial in advocating for the HPV vaccine. Interventions that occur now, as the student is still developing identity as a citizen, professional, and religious follower, have the potential to shape adult choices about vaccinating children later in life. Examples of interventions that employ these context-specific approaches include: (a) an on-campus vaccination campaign designed with and implemented by students who espouse religious views that are otherwise similar to the target population or (b) parent focus groups with religious leaders of individual worshipping communities to discuss HPV vaccination in a sensitive but tailored way.Empowering college students to learn more about how vaccines work and their processes for safety approval by the Food and Drug Administration (FDA) may result in future parents, community leaders, and healthcare providers who are more confident in their own assessment of the utility of a vaccine, thereby increasing long-term HPV vaccination rates in the US. Interestingly, 73.2% of our study population reported a degree in the STEM field, including pre-healthcare professions . Among tIn conclusion, our findings suggest that emphasis on education about the utility of the HPV vaccine despite devotion to particular religious practices is necessary. Focusing on the necessity of the vaccine for life-long protection against HPV and HPV-related cancers will serve to not only promote catch-up vaccination rates among college-aged individuals but further aid in increasing the vaccination rates of future generations. Extensive efforts must be made by healthcare providers to disentangle religious and safety concerns from the efficacy of the HPV vaccine. In addition, the reevaluation of the undergraduate curriculum, particularly in the STEM departments, regarding vaccine safety may be particularly urgent in the wake of the COVID-19 pandemic and subsequent political debates. Finally, partnerships to address HPV and cervical cancer awareness with sensitivity to religious beliefs among specific worshipping populations or student groups may be an effective and tailored way to increase HPV vaccination rates.While we found faith-based beliefs and safety concerns to be indicators of acceptance of the HPV vaccine in the study population, multiple other factors may influence a person’s decision to vaccinate a child against HPV that were not examined. Other indicators not assessed in our survey might include concerns regarding personal autonomy, presence or absence of provider recommendation, extent of government mistrust, desire for “natural” living free of drugs or biologicals, and political affiliation. Further, students with the strongest level of mistrust of science or resistance to vaccination may have refused the survey; the views of these students are thus not reflected in our results. Additionally, our recruitment method (professors offering extra credit to students in their courses) may have introduced selection bias based on the professors’ motivations for participation or communicated opinions regarding vaccination. Finally, our findings are based on convenience sampling of one university in the geographical south and may not fully reflect the views of all religious college students in the US. For example, our student population includes low proportions of Muslim, Hindu, and Jewish students; it also included a very low number of students who associate with no religion. Therefore, reasons for vaccination resistance among atheist or agnostic students could not be determined.As a cross-sectional study, this is unable to establish causation. However, understanding the correlates to HPV vaccine attitudes suggests areas where educational interventions may be effective. Further work is necessary to see if interventions in the identified correlations are effective at influencing vaccine attitudes.