Immunosuppression and cancer risk in kidney transplant recipients: A retrospective cohort study.

We assessed whether contemporary immunosuppression agents were associated with cancer among kidney transplant recipients (KTR), and if this association varied by age and sex. We studied a retrospective province-wide cohort of primary KTR (1997-2016). Employing multivariable Cox models, we estimated associations of cumulative doses of prednisone, mycophenolate and tacrolimus administered over the past 10 years, lagged by 2 years, with the incidence of primary malignant neoplasms (PMN). We assessed interactions with age and sex. To assess the impact of exposure recency, we used weighted cumulative exposure (WCE) modeling. Among 1064 KTR, 108 (10.2%) developed PMN over median follow-up of 73 months (interquartile range: 32-120). Adjusted hazard ratios (aHRs) and 95% confidence intervals (CIs) of 0.96 (0.64-1.43), 1.34 (0.96-1.86), and 1.06 (0.88-1.29) were estimated for cumulative daily doses of prednisone (5 mg), mycophenolate (1000 mg), and tacrolimus (2 mg) administered continuously over the past 10 years, respectively. PMN risk associated with cumulative tacrolimus exposure was modified by age (interaction p = .035) and was more pronounced in 15-year and 30-year-old KTR (aHRs of 1.57 [1.08-2.28] and 1.31 [1.03-1.66], respectively) in comparison to older KTR. PMN risk increase associated with higher cumulative mycophenolate dose was more pronounced in females (aHR = 1.86 [1.15-3.00]) than in males (aHR = 1.16 [0.74-1.81]; interaction p = .131). WCE analyses suggested increased PMN risk the higher the mycophenolate doses taken 5-10 years ago. A trend toward increased PMN risk with long-term mycophenolate exposure, particularly in females, and more pronounced risk with long-term tacrolimus exposure in younger KTR, identify opportunities for tailored immunosuppression to mitigate cancer risk.

Rates of out-of-home care among children in Canada: an analysis of national administrative child welfare data. / Taux de placement des enfants hors de leur foyer familial : analyse des données administratives nationales du système de protection de l'enfance au Canada.

INTRODUCTION: As a part of the public health approach to child welfare, data about children placed in out-of-home care are needed to assess population trends, understand drivers of social and health inequities, and examine outcomes for children and families. We analyzed administrative data from Canada to describe the population of children in out-of-home care, and estimate and compare rates of out-of-home care by province/territory, year, sex/gender, age group and placement type. METHODS: We conducted a cross-sectional analysis of point-in-time data from all provinces and territories for the period 2013/2014 to 2021/2022. We used frequencies and percentages to describe the population of children (and youth up to age 21 years) in out-of-home care and estimated overall and stratified rates and rate ratios. RESULTS: An estimated 61 104 children in Canada were in out-of-home care on 31 March 2022. The national rate of out-of-home care was 8.24 children per 1000 population. Rate variations by province/territory were substantial and changed over time. Rates were highest among males and children aged 1 to 3 and 16 to 17 years. Foster homes were the most common type of placement, although kinship homes accounted for an increasing share. CONCLUSION: This analysis demonstrated that administrative data can be used to generate national indicators about children involved in the child welfare system. These data can be used for tracking progress towards health and social equity for children and youth in Canada.

Human Papillomavirus Concordance Between Parents and Their Newborn Offspring: Results From the Finnish Family Human Papillomavirus Study.

BACKGROUND: The knowledge on vertical human papillomavirus (HPV) transmission is limited. We aimed to determine whether HPV transmission from parents to their offspring occurs before or during birth. METHODS: Altogether, 321 mothers, 134 fathers, and their 321 newborn offspring from the Finnish Family HPV study cohort were included. Parents' genital and oral brush samples and semen samples were collected for HPV testing at baseline (36 weeks of pregnancy). Oral, genital, and umbilical samples from the newborn and placenta samples were collected for HPV testing immediately after delivery. HPV risk for the newborn was calculated from the mother's and father's HPV status by using logistic regression analyses. RESULTS: Concordances between mothers' and their newborns' HPV genotype at any site were statistically significant with HPV-6, -16, -18, -31, and -56; odds ratios (ORs) ranged from 3.41 (95% confidence interval [CI], 1.80-6.48) for HPV-16 to 634 (95% CI, 28.5-14 087) for HPV-31. Father-newborn HPV concordance was statistically significant with HPV-6 and HPV-31 (ORs, 4.89 [95% CI, 1.09-21.9] and 65.0 [95% CI, 2.92-1448], respectively). CONCLUSIONS: The genotype-specific HPV concordance between parents and their newborn is suggestive for vertical HPV transmission. However, transmission from the father to the newborn remains more uncertain.

Patterns and motivations of polysubstance use: a rapid review of the qualitative evidence. / Tendances et motivations associées à la polyconsommation de substances : une revue rapide des données qualitatives.

INTRODUCTION: Polysubstance use-the use of substances at the same time or close in time-is a common practice among people who use drugs. The recent rise in mortality and overdose associated with polysubstance use makes understanding current motivations underlying this pattern critical. The objective of this review was to synthesize current knowledge of the reasons for combining substances in a single defined episode of drug use. METHODS: We conducted a rapid review of the literature to identify empirical studies describing patterns and/or motivations for polysubstance use. Included studies were published between 2010 and 2021 and identified using MEDLINE, Embase, PsycINFO and Google Scholar. RESULTS: We included 13 qualitative or mixed-method studies in our analysis. Substances were combined sequentially to alleviate withdrawal symptoms or prolong a state of euphoria ("high"). Simultaneous use was motivated by an intention to counteract or balance the effect(s) of a substance with those of another, enhance a high or reduce overall use, and to mimic the effect of another unavailable or more expensive substance. Self-medication for a pre-existing condition was also the intention behind sequential or simultaneous use. CONCLUSION: Polysubstance use is often motivated by a desire to improve the experience based on expected effects of combinations. A better understanding of the reasons underlying substance combination are needed to mitigate the impact of the current overdose crisis.

Understanding barriers and facilitators to HIV testing in Canada from 2009-2019: A systematic mixed studies review.

BACKGROUND: HIV testing is a core pillar of Canada's approach to sexually transmitted and blood-borne infection (STBBI) prevention and treatment and is critical to achieving the first Joint United Nations Programme on HIV/AIDS (UNAIDS) 90-90-90 target. Despite progress toward this goal, many Canadians remain unaware of their status and testing varies across populations and jurisdictions. An understanding of drivers of HIV testing is essential to improve access to HIV testing and reach the undiagnosed. OBJECTIVE: To examine current barriers and facilitators of HIV testing across key populations and jurisdictions in Canada. METHODS: A systematic mixed studies review of peer-reviewed and grey literature was conducted identifying quantitative and qualitative studies of barriers and facilitators to HIV testing in Canada published from 2009 to 2019. Studies were screened for inclusion and identified barriers and facilitators were extracted. The quality of included studies was assessed and results were summarized. RESULTS: Forty-three relevant studies were identified. Common barriers emerge across key populations and jurisdictions, including difficulties accessing testing services, fear and stigma surrounding HIV, low risk perception, insufficient patient confidentiality and lack of resources for testing. Innovative practices that could facilitate HIV testing were identified, such as new testing settings (dental care, pharmacies, mobile units, emergency departments), new modalities (oral testing, peer counselling) and personalized sex/gender and age-based interventions and approaches. Key populations also face unique sociocultural, structural and legislative barriers to HIV testing. Many studies identified the need to offer a broad range of testing options and integrate testing within routine healthcare practices. CONCLUSION: Efforts to improve access to HIV testing should consider barriers and facilitators at the level of the individual, healthcare provider and policy and should focus on the accessibility, inclusivity, convenience and confidentiality of testing services. In addition, testing services must be adapted to the unique needs and contexts of key populations.

Detection of Fusobaterium nucleatum in feces and colorectal mucosa as a risk factor for colorectal cancer: a systematic review and meta-analysis.

BACKGROUND: Colorectal cancer (CRC) is a major cause of cancer deaths worldwide. Accumulating evidence suggests a potentially important role of colorectal infection with Fusobacterium nucleatum (F. nucleatum) in colorectal carcinogenesis. We conducted a systematic review, including both a qualitative synthesis and a meta-analysis, to synthesize the evidence from the epidemiological literature on the association between F. nucleatum detection in the colon/rectum and CRC. METHODS: A systematic literature search of Ovid MEDLINE(R), Embase, Web of Science Core Collection, EBM Reviews-Cochrane Database of Systematic Reviews, and CINAHL Plus with Full Text was conducted using earliest inclusive dates up to 4 October 2020. Eligible studies were original, comparative observational studies that reported results on colorectal F. nucleatum detection and CRC. Two independent reviewers extracted the relevant information. Odds ratio (OR) estimates were pooled across studies using the random effects model. Newcastle-Ottawa scale was used to critically appraise study quality. RESULTS: Twenty-four studies were included in the systematic review, of which 12 were included in the meta-analysis. Studies investigated F. nucleatum in feces, colorectal tissue samples, or both. In most studies included in the systematic review, the load of F. nucleatum was higher, on average, in specimens from CRC patients than in those from CRC-free controls. Meta-analysis showed a positive association between F. nucleatum detection in colorectal specimens and CRC (OR = 8.3; 95% confidence interval (95% CI) 5.2 to 13.0). CONCLUSIONS: The results of this systematic review suggest that F. nucleatum in the colon/rectum is associated with CRC. SYSTEMATIC REVIEW REGISTRATION: This systematic review protocol has been registered with the International Prospective Register of Systematic Reviews (PROSPERO) on July 10, 2018 (registration number CRD42018095866).

Treatment Switch to Dolutegravir With 2 Nucleoside Reverse-Transcriptase Inhibitors (NRTI) in Comparison to Continuation With Protease Inhibitor/Ritonavir Among Patients With Human Immunodeficiency Virus at Risk for Prior NRTI Resistance: A Cohort Analysis of Real-World Data.

BACKGROUND: Switching antiretroviral regimens when human immunodeficiency virus (HIV) viremia is controlled for a new regimen is challenging when there is the potential for prior nucleoside reverse-transcriptase inhibitor (NRTI) resistance. The objective was to study virologic outcomes after switching to dolutegravir compared with remaining on a boosted protease inhibitor (protease inhibitor/ritonavir [PI/r]) regimen in people with HIV (PWH) with prior documented virologic failure and/or exposure to mono/dual NRTIs. METHODS: We used the Quebec HIV Cohort including 10 219 PWH whose data were collected at 4 sites in Montreal, Canada. We included all PWH with documented virologic failure or exposure to mono/dual NRTI therapy who were virologically suppressed on a PI/r-based regimen for at least 6 months on or after January 1, 2014 (n = 532). A marginal structural Cox model analysis was used to estimate the effect of the switch to dolutegravir on virologic outcome compared with remaining on PI/r. The outcome was defined as 2 consecutive viral loads (VLs) >50 copies/mL or 1 VL >50 copies/mL if it occurred at the last VL available. RESULTS: Among 532 eligible participants, 216 (40.6%) had their regimen switched to dolutegravir with 2 NRTIs, whereas 316 (59.4%) remained on the PI/r with 2 NRTIs. The weighted hazard ratio for the effect of dolutegravir switch on virologic failure compared with patients whose regimen remained on PI/r was 0.57 (95% confidence interval, 0.21-1.52). CONCLUSIONS: We did not find evidence of an increased risk for virologic failure after switching to dolutegravir from PI/r among patients with previous virologic failure or prior exposure to mono/dual NRTI.

Impact of previous HIV resistance and virologic failures on virologic outcome following a switch to dolutegravir with 2 NRTIs among people living with HIV.

There is uncertainty regarding the potential virologic outcome associated with a change in antiretroviral therapy (ARV) among PLHIV who had previous documented virologic failure or who have been exposure to mono/dual nucleoside reverse transcriptase inhibitors (NRTI) therapy. The objective was to measure the potential impact of exposure to previous virologic failure or mono/dual NRTI regimen on virologic outcome of PLHIV following a switch to dolutegravir with 2 NRTIs from a viremia suppressive ARV therapy.Data from the Quebec HIV Cohort including 10219 PLHIV were collected through routine clinical care at 4 clinical sites in Montreal, Canada. This study includes patients whose ARV therapy was switched to dolutegravir with 2 NRTIs since 2013 with undetectable viral load for ≥6 months before switch. The association between exposure and post-switch virologic outcome was measured by marginal hazard ratio estimated using the Inverse probability weighting Cox model.Among the 1199 eligible PLHIV, 478 (39.9%) previously experienced at least one virologic failure or were exposed to mono/dual therapy before dolutegravir switch. Post-switch virologic failure after 30 months occurred in 4.1% (95% CI 2.1-7.9) of exposed compared to 4.1% (95% CI 2.3-7.4) in unexposed participants. The adjusted hazard ratio for the association between exposure and post-switch virologic failure was 0.84 (95% CI 0.35-2.01).Our findings suggest that switch to dolutegravir with 2 NRTIs from a suppressive therapy is a safe option for PLHIV with documented virologic failure and/or previous exposure to mono/dual NRTI therapy.

Cumulative risk of cervical intraepithelial neoplasia for women with normal cytology but positive for human papillomavirus: Systematic review and meta-analysis.

Most women positive for human papillomavirus (HPV) are cytology normal. The optimal screen-management of these women is unclear given their risk of developing precancer. We performed a systematic review and meta-analysis of progression rates to precancer and cancer for HPV-positive, cytology normal women. We searched MEDLINE, EMBASE and Scopus for prospective studies measuring the cumulative incidence of precancer and cervical cancer in HPV-positive, cytology/histology normal women. Record screening was performed independently by two reviewers. We modeled the cumulative incidence over time using a multilevel random-effects meta-regression model. We used the model to predict HPV type-specific risks of precancer and cancer over follow-up. Data from 162 unique records were used in our analysis. The average incidence rate of cervical intraepithelial neoplasia grade 3 or cancer (CIN3+) in high-risk HPV positive but cytology/histology normal women was 1.0 per 100 women-years (95% CI: 1.0-1.1). This corresponds to an average cumulative risk at 1, 3 and 5 years of 2.1% (95% prediction interval 0.0-9.5), 4.3% (95% prediction interval 0.0-11.5) and 6.4% (95% prediction interval 0.0-13.5). HPV type was a strong predictor of the risk of oncogenic progression. There was substantial heterogeneity in the background precancer risk across studies (P-value < .0001). Our HPV type-specific progression risk estimates can help inform risk-based cervical cancer screening guidelines for HPV-positive women. However, precancer and cervical cancer risks are highly variable and may not be generalizable between populations.

Occult Tubal Carcinoma After Risk-Reducing Salpingo-oophorectomy: A Systematic Review.

OBJECTIVE: To perform a systematic review of the literature to estimate the prevalence and outcomes of occult tubal carcinoma in BRCA mutation carriers and high-risk patients undergoing risk-reducing salpingo-oophorectomy. DATA SOURCE: A search was done using OVID MEDLINE, EMBASE, and ClinicalTrials.gov between 1946 and March 2019 with keywords and MeSH terms selected by an expert medical librarian and coauthors. METHODS OF STUDY SELECTION: Two independent reviewers performed study selection with an initial screen on abstracts and a second on full articles. Articles were rejected if they were irrelevant to the study question, pertained to a different population or did not report occult tubal neoplasia. Quality was assessed using methodologic index for nonrandomized studies criteria. TABULATION, INTEGRATION, AND RESULTS: Data were extracted and recorded in an Excel database. Forest plots for the prevalence of occult carcinoma were done using STATA. Among 2,402 studies assessed, 27 met the inclusion criteria for qualitative and quantitative analysis. A total of 6,283 patients underwent risk-reducing salpingo-oophorectomy between 2002 and 2019: 2,894 cases were BRCA1, 1,579 BRCA2, and 1,810 high-risk based on family history. Among these, 75 patients were diagnosed with occult tubal carcinoma at the time of surgery. The pooled prevalence was 1.2% (I=7.1%, P=.363) occurring at a median age of 53.2 years (range 42.4-67). In a subanalysis of 18 studies reporting follow-up data, 10 recurrences (18.7%, 95% CI 7.5-53%) and 24 cases of post-risk-reducing salpingo-oophorectomy peritoneal cancer (0.54%, 95% CI 0.4-1.9%) were reported after a median follow-up of 52.5 months. BRCA1, older age, and previous breast cancer were more often associated with occult malignancy. CONCLUSION: Occult tubal carcinomas found at risk-reducing salpingo-oophorectomy in high-risk patients and BRCA mutation carriers have significant potential for recurrence despite the frequent administration of postoperative chemotherapy.

Sex and Gender Considerations in Transplant Research: A Scoping Review.

BACKGROUND: In response to the promotion of sex and gender integration in health-related research, we conducted a scoping review evaluating to what extent sex and gender were considered in the transplantation literature. METHODS: We searched Medline and Embase for manuscripts published between January 1946 and October 2016. Two reviewers independently selected manuscripts describing clinical research on stem cells, tissues, or solid organ transplantation with ≥20 participants, which mentioned "sex" and/or "gender" in the title or abstract. For each eligible manuscript, 2 of 5 reviewers extracted data on study design, population (transplant candidates, recipients, donors), transplant type, and study outcomes. We evaluated whether the terms "sex" and "gender" were applied according to their correct definitions and how these variables were handled at the level of study design and analysis. RESULTS: Of 7565 search results, 2107 manuscripts met the inclusion criteria. Sex and gender were applied interchangeably in more than half of the studies (57.5%). Rarely were sex or gender, when applied correctly, considered in the primary study question (13.3% and 25.0%, respectively). The majority of the studies considered these variables as confounders (74.6% for sex and 68.2% for gender), and a minority considered them as effect measure modifiers (2.8% for sex and 5.0% for gender). CONCLUSIONS: Despite a growing awareness of the need to integrate sex and gender in health research, education is required to ensure accurate and meaningful consideration of these concepts. We outline strategies for integrating sex and gender in allotransplantation and donation research during study design and analysis.

Increased risk of oropharyngeal cancers mediated by oral human papillomavirus infection: Results from a Canadian study.

BACKGROUND: This study aimed to estimate the extent to which oral sex behavior is associated with an increased risk of oropharyngeal cancers (OPCs), and how much of the association is mediated by oral human papillomavirus (HPV) infection. METHODS: We used data from a hospital-based case-control study conducted in Montreal, Canada. Information on oral sex behaviors was collected. Oral rinse and oral brush specimens were analyzed for HPV positivity and genotyping. Logistic regression estimated the odds ratios (OR) and 95% confidence intervals (CI) for the association between oral sex behaviors and OPC. RESULTS: Onset of oral sex practice at age 16 years or younger had an increased risk of OPCs relative to those with onset after age 30 years (OR = 2.98; 95% CI 1.37-6.47). This association decreased (OR = 1.09; 95% CI 0.25-4.71) when restricted to those positive for HPV. CONCLUSIONS: Our results suggest that the association between oral sex and OPC seems mediated by oral HPV infection.

The relationship between body-mass index, physical activity, and pathologic and clinical outcomes after radical prostatectomy for prostate cancer.

PURPOSE: We evaluated whether an increased body-mass index (BMI) and decreased physical activity increase the risk of locally advanced or high-risk prostate cancer (PCa) at radical prostatectomy (RP), and treatment failure after surgery. METHODS: Data were collected from the PROCURE Biobank, a prospective cohort of patients with localized PCa undergoing RP in four academic centers in Québec between 2006 and 2013. Treatment failure was defined as biochemical recurrence and/or initiation of secondary, non-adjuvant therapy, and analyzed using the Kaplan-Meier method, log-rank tests, and Cox proportional-hazards models. Uni- and multivariate (ordered) logistic regression was used for time-independent variables. RESULTS: 1813 patients were included. Median follow-up time was 69 months. Patients who reported a lower BMI were generally older, of Asian descent, and physically more active (p < 0.05). Younger, black, and overweight/obese patients reported less physical activity (p < 0.05). In multivariate analyses, a higher BMI increased the risk for locally advanced, high-risk PCa (defined as a pT3, N1 and/or Gleason 8-10 tumor; odds ratio 1.33, p < 0.001), but increased physical activity did not predict high-risk disease (odds ratio 0.84, p = 0.39). Patients with a higher BMI also had a larger prostate at surgery (odds ratio 1.13, p = 0.03). BMI and physical activity were not associated with positive surgical margins or time to treatment failure (p > 0.05). CONCLUSIONS: BMI was an independent predictor for locally advanced, high-risk disease in this cohort of PCa patients undergoing RP, but was unrelated to treatment failure. Physical activity was not related to locally advanced, high-risk PCa or treatment failure.

Risk of lip cancer after solid organ transplantation in the United States.

Solid organ transplant recipients have an increased risk of lip cancer, but the reasons are uncertain. Using data from the Transplant Cancer Match Study, we describe the epidemiology of lip cancer among 261 500 transplant recipients in the United States. Two hundred thirty-one lip cancers were identified, corresponding to elevated risks for both invasive and in situ lip cancers (standardized incidence ratios of 15.3 and 26.2, respectively). Invasive lip cancer incidence was associated with male sex (adjusted incidence rate ratio [aIRR] 2.01, 95% CI 1.44-2.82), transplanted organ (0.33, 0.20-0.57, for liver transplants and 3.07, 1.96-4.81, for lung transplants, compared with kidney transplants), and racial/ethnic groups other than non-Hispanic whites (0.09, 0.04-0.2). In addition, incidence increased with age and during the first 3 years following transplant, and was higher in recipients prescribed cyclosporine/azathioprine maintenance therapy (aIRR 1.79, 95% CI 1.09-2.93, compared with use of tacrolimus/mycophenolate mofetil) and following a diagnosis of cutaneous squamous cell carcinoma (4.21, 2.69-0.94). The elevation in lip cancer incidence is consistent with an effect of immunosuppression. Notably, the very strong associations with white race and history of prior skin cancer point to an important role for ultraviolet radiation exposure, and cyclosporine and azathioprine may contribute as photosensitizing or DNA damaging agents.

Exposure to Low-Dose Ionizing Radiation From Cardiac Procedures and Malignancy Risk in Adults With Congenital Heart Disease.

BACKGROUND: Adults with congenital heart disease (CHD) are exposed to increasing amounts of low-dose ionizing radiation (LDIR) from cardiac procedures. Cancer prevalence in this population is higher than in the general population. This study estimates the association between LDIR exposure from cardiac procedures and incident cancer in adult patients with CHD. METHODS: The study population derived from the Quebec Congenital Heart Disease Database. We measured cumulative numbers of LDIR-related cardiac procedures for each patient until 1 year before the time of cancer diagnosis or administrative censoring. To assess the association between LDIR exposure and cancer risk, we conducted a nested case-control study and matched cancer cases with controls on sex, CHD severity, birth year, and age. RESULTS: The study included 24 833 adult patients with CHD aged 18 to 64 years from 1995 to 2009. In >250 791 person-years of follow-up, 602 cancer cases were observed (median age, 55.4 years). The cumulative incidence of cancer estimated up to 64 years of age was 15.3% (95% confidence interval [CI], 14.2-16.5). Cases had more LDIR-related cardiac procedures than controls (1410 versus 921 per 1000 adult patients with CHD, P<0.0001). Cumulative LDIR exposure was independently associated with cancer (odds ratio [OR], 1.08 per procedure; 95% CI, 1.04-1.13). Similar results were obtained by using dose estimates for LDIR exposure (OR, 1.10 per 10 mSv; 95% CI, 1.05-1.15) with a possible dose-related response. The effect measure was in the same direction, and the association was persistent for exposure from ≥6 procedures in all sensitivity analyses: after excluding most smoking-related cancer cases (OR, 1.10 per procedure; 95% CI, 1.05-1.16 and OR when exposure from ≥6 procedures, 3.08; 95% CI, 1.77-5.37), and after applying a 3-year lag period (OR, 1.09 per procedure; 95% CI, 1.03-1.14 and OR when exposure from ≥6 procedures: 2.58; 95% CI, 1.43-4.69). CONCLUSIONS: To our knowledge, this is the first large population-based study to analyze and document the association between LDIR-related cardiac procedures and incident cancer in the population of adults with CHD. Confirmations of these findings by prospective studies are needed to reinforce policy recommendations for radiation surveillance in patients with CHD where no regulation currently exists. Physicians ordering and performing cardiac imaging should ensure that exposure is as low as reasonably achievable without sacrificing quality of care.

Sex and gender considerations in transplantation research: protocol for a scoping review.

BACKGROUND: Despite the growing appreciation of the importance of sex and gender considerations in transplantation research, there is currently no framework or good practice guidelines for the appropriate handling of sex and gender issues in human allotransplantation research. METHODS: We will conduct a scoping review to synthesize the evidence on how matters of sex and gender have been handled in human allotransplantation research. We will survey the literature discussing sex and gender in relation to transplantation, including adult and pediatric patients, hematopoietic and solid organ transplant recipients as well as organ donors. We will search MEDLINE and Embase for literature discussing sex and gender in relation to transplantation. Two reviewers will independently evaluate the eligibility of all identified titles and abstracts for inclusion in the full text review, as well as data extraction. Descriptive data and information on how sex and gender have been considered in human transplantation research will be reported. DISCUSSION: This scoping review will be an important stepping stone towards the development of good practice guidelines on study design and analysis considerations when handling sex and gender issues in human transplantation research. This scoping review can also help identify methodological issues that restrict the translation of transplantation research findings into clinical practice related to underestimation of sex/gender differences. This review will ultimately identify major gaps, inform donor-recipient selection, guide personalized interventions, and prioritize research recommendations in human transplantation research.

Human papillomavirus genotypes and risk of head and neck cancers: Results from the HeNCe Life case-control study.

OBJECTIVE: Human papillomaviruses (HPV) are changing dramatically the epidemiologic landscape of head and neck cancers (HNCs). Their role in the aetiology of these cancers varies widely among HNCs subsites, sex and geographical regions worldwide. We describe HPV prevalence and its association with HNCs risk overall and by anatomical subsite in a sample of Canadians. MATERIALS AND METHODS: The HeNCe Life study recruited 460 incident HNCs cases and 458 controls frequency-matched by age and sex from four Montreal hospitals in 2005-2013. We tested oral rinse and oral brush specimens for mucosal HPV genotypes. HPV positivity was categorized hierarchically as either negative, exclusively non-α-9 species types, α-9 types other than HPV16, and HPV16. We estimated odds ratios (OR) and 95% confidence intervals (CI) for the associations between HPV and HNCs using unconditional logistic regression, controlling for confounders. RESULTS: The prevalence of HPV infection among controls and cases was 14.5% and 41.2% in oral rinse and 3.1% and 24.4% in oral brush samples, respectively. HPV16 was the predominant genotype with an oral rinse and oral brush prevalence of 26.3% and 16.2% among cases and 2.4% and 0.2% among controls, respectively. HPV infection was associated with an increased risk of HNCs overall (OR=4.18; 95% CI, 2.94-5.95) and oropharyngeal cancer only (OR=10.3; 95% CI, 6.8-15.7). HNCs and oropharyngeal cancer were strongly associated with HPV16 (OR=18.1; 95% CI, 9.1-35.8, and OR=47.2; 95% CI, 23.1-96.6, respectively). CONCLUSION: HPV infection, particularly HPV16, was associated with an increased HNCs risk, most strongly for oropharyngeal cancers.

Periodontal diseases and risk of oral cancer in Southern India: Results from the HeNCe Life study.

Some studies suggest that periodontal diseases increase the risk of oral cancer, but contradictory results also exist. Inadequate control of confounders, including life course exposures, may have influenced prior findings. We estimate the extent to which high levels of periodontal diseases, measured by gingival inflammation and recession, are associated with oral cancer risk using a comprehensive subset of potential confounders and applying a stringent adjustment approach. In a hospital-based case-control study, incident oral cancer cases (N = 350) were recruited from two major referral hospitals in Kerala, South India, from 2008 to 2012. Controls (N = 371), frequency-matched by age and sex, were recruited from clinics at the same hospitals. Structured interviews collected information on several domains of exposure via a detailed life course questionnaire. Periodontal diseases, as measured by gingival inflammation and gingival recession, were evaluated visually by qualified dentists following a detailed protocol. The relationship between periodontal diseases and oral cancer risk was assessed by unconditional logistic regression using a stringent empirical selection of potential confounders corresponding to a 1% change-in-estimates. Generalized gingival recession was significantly associated with oral cancer risk (Odds Ratio = 1.83, 95% Confidence Interval: 1.10-3.04). No significant association was observed between gingival inflammation and oral cancer. Our findings support the hypothesis that high levels of periodontal diseases increase the risk of oral cancer.

No role for human papillomavirus infection in oral cancers in a region in southern India.

Oral cancer is a major public health issue in India with ∼ 77,000 new cases and 52,000 deaths yearly. Paan chewing, tobacco and alcohol use are strong risk factors for this cancer in India. Human papillomaviruses (HPVs) are also related to a subset of head and neck cancers (HNCs). We examined the association between oral HPV and oral cancer in a sample of Indian subjects participating in a hospital-based case-control study. We recruited incident oral cancer cases (N = 350) and controls frequency-matched by age and sex (N = 371) from two main referral hospitals in Kerala, South India. Sociodemographic and behavioral data were collected by interviews. Epithelial cells were sampled using Oral CDx® brushes from the oral cancer site and the normal mucosa. Detection and genotyping of 36 HPV genotypes were done using a polymerase chain reaction protocol. Data collection procedures were performed by qualified dentists via a detailed protocol with strict quality control, including independent HPV testing in India and Canada. HPV DNA was detected in none of the cases or controls. Associations between oral cancer and risk factors usually associated with HPV infection, such as oral sex and number of lifetime sexual partners, were examined by logistic regression and were not associated with oral cancer. Lack of a role for HPV infection in this study may reflect cultural or religious characteristics specific to this region in India that are not conducive to oral HPV transmission. A nationwide representative prevalence study is needed to investigate HPV prevalence variability among Indian regions.