Pierre-Paul Tellier

Modifiable Risk Factors Associated with Clearance of Type-Specific Cervical Human Papillomavirus Infections in a Cohort of University Students

Background: Previous findings regarding risk factors for human papillomavirus (HPV) persistence, other than viral determinants, identified from prospective cohort studies have been inconsistent in part because study designs have differed with respect to differing HPV detection methods and varying lengths of follow-up time. Therefore, the objectives of this study were to continue the search for epidemiologic risk factors of persistent cervical HPV infections and determine what behaviors differed between those women with transient HPV infections and those women who cannot clear their type-specific HPV infections. Methods: Female university students (n = 621) in Montreal were followed for 24 months at 6-month intervals. At each visit, a cervical cell specimen was collected. HPV DNA was detected using the MY09/MY11 PCR protocol and 27 HPV genotypes were identified by the line blot assay (Roche Molecular Systems, Inc., Alameda, CA). Proportional hazards regression was used to estimate the crude and adjusted hazard ratios of clearing a type-specific high-risk (n = 222) or low-risk (n = 105) HPV infection over time according to specific baseline and time-dependent covariates. Results: Daily consumption of vegetables seemed to increase the rate of HPV clearance independent of type. The use of tampons was associated with a reduced rate of high-risk HPV clearance, whereas regular condom use was associated with an increased rate of low-risk HPV clearance only. Conclusion: Some proactive measures can be taken to increase the rate of HPV clearance, and there may be some differences between the sets of predictors of low-risk and high-risk HPV clearance.

Human papillomavirus infections among couples in new sexual relationships.

Background: No studies have examined human papillomavirus (HPV) infections among couples early in their sexual relationships when transmission is most likely. Our objective was to describe the distribution of HPV infections among recently formed couples, using the partnership as the unit of analysis. Methods: Women aged 18–24 years attending a university or junior college in Montreal enrolled in a longitudinal study with their new male partners. Self-collected vaginal swabs and clinician-collected swabs from the penis and scrotum were tested for 36 HPV genotypes. Participants self-reported sexual behavior in computerized questionnaires. We analyzed patterns of genital HPV infection in 263 couples using data obtained at enrollment. Results: Couples had engaged in vaginal sex for a median of 3.9 months. HPV was detected in 64% (169/263) of couples. In 41% (109/263), both partners harbored the same HPV type—nearly 4 times more than expected if HPV status of partners were uncorrelated. There were 583 type-specific HPV infections among 169 couples for whom at least one partner was infected. Of these, 42% were of the same type for both partners (95% confidence interval = 36%–47%). This rose from 25% among those engaging in vaginal sex for less than 2 months to 68% among those at 5 to 6 months. Conclusions: Although HPV is common, detection of the same type in persons initiating a sex relationship would be rare given type-specific prevalence rates. The high degree of concordance we found suggests a high probability of transmission.

Genital Transmission of Human Papillomavirus in Recently Formed Heterosexual Couples

We estimated human papillomavirus (HPV) transmission rates among persons with documented sexual exposure to an infected partner. Recently formed couples enrolled in the HITCH Study (HPV Infection and Transmission among Couples through Heterosexual activity) in Montreal, Canada, and provided genital specimens for DNA testing of 36 HPV genotypes. At enrollment, 179 couples were discordant for ≥1 HPV types; transmission was observed at follow-up in 73 partnerships. There was little difference between the male-to-female (3.5 per 100 person-months, 95% confidence interval [CI], 2.7-4.5) and female-to-male (4.0 per 100 person-months, 95% CI, 3.0-5.5) transmission rates. Rates did not vary with the lifetime number of partners reported by the initially uninfected partner, providing no evidence of reduced susceptibility for those with extensive sexual histories. Transmission was also relatively homogeneous across HPV genotypes and alpha species and oncogenic risk categories. The findings contribute to a small but growing evidence base regarding the natural history of HPV transmission.

Human leukocyte antigen (HLA)-E and HLA-G polymorphisms in human papillomavirus infection susceptibility and persistence

Human leukocyte antigen (HLA)-E and HLA-G molecules act as powerful modulators of innate and adaptive immune responses. The study examined whether HLA-E and/or HLA-G polymorphisms are associated with human papillomavirus (HPV) infection susceptibility and persistence in 636 female university students in Montreal. HLA-G*01:01:02 and HLA-G*01:01:08 alleles were associated with increased risk of HPV-16 (odds ratio (OR) = 2.10, 95% confidence interval (CI), 1.11-3.96) and any infections with HPV types from α species 1, 8, 10, and 13 (OR = 2.72, 95% CI, 1.11-6.68). HLA-G*01:01:02 and HLA-G*01:03 alleles were associated with persistent HPV-16 (OR = 2.07, 95% CI, 1.16-3.68) and persistent infections with HPV types from α species 2, 3, 4, and 15 (OR = 2.99, 95% CI, 1.12-8.00). HLA-E polymorphism was not associated with risk of acquisition or persistence of HPV infection. These results suggest that HLA-G molecules may play a role in mediating HPV infection risk.

HLA Polymorphisms and Cervical Human Papillomavirus Infection in a Cohort of Montreal University Students

BACKGROUND Only a minority of women with human papillomavirus (HPV) infection eventually develop cervical cancer, which suggests that host immune mechanisms play a role in the disease. HLA polymorphisms have been linked to the risk of cervical cancer, but very little is known about the role that they play in the acquisition and persistence of HPV infection. METHODS A cohort study of cervical HPV infections was used to examine the role that 5 HLA alleles (B*07, DQB1*03, DQB1*0602, DRB1*13, and DRB1*1501) play in determining the risk of HPV positivity and persistence in 524 female university students in Montreal. HPV positivity was determined by use of the MY09/11 polymerase-chain-reaction protocol. HLA alleles from purified DNA from cervical specimens were typed by use of a polymerase-chain-reaction technique using sequence-specific primers. RESULTS HLA DRB1*13 was associated with cumulative risk of HPV infections (odds ratio [OR], 1.7 [95% confidence interval {CI}, 1.0-2.8]), for oncogenic HPV (OR, 1.6 [95% CI, 0.9-2.8]), and for HPV-16 (OR, 2.0 [95% CI, 0.9-4.4]). DQB1*03 was consistently associated with a lower cumulative risk of HPV infections, but this association was not statistically significant. None of the alleles affected the risk of HPV persistence. CONCLUSIONS The results of this study support the hypothesis that certain HLA class II polymorphisms mediate genetic susceptibility to the acquisition of HPV infection.

Influence of partner's infection status on prevalent human papillomavirus among persons with a new sex partner.

Background: We evaluated the influence of the partners human papillomavirus (HPV) status and sexual practices on prevalent HPV infection among new couples to study HPV transmission. Methods: Women attending university or college in Montreal, Canada, and their male partners (N = 263 couples) were enrolled in 2005–2008. HPV typing was done in self-collected vaginal swabs and clinician-collected penis and scrotum swabs. The outcome measures were overall and type-specific HPV prevalence. Results: HPV was detected in 56% of women and men. Prevalence was higher among persons with infected partners (85%) than in those whose partners were negative (19%). Type-specific detection was substantially higher among women (OR = 55.2, 95% CI: 38.0–80.1) and men (OR = 58.7, 95% CI: 39.8–86.3) if their partner harbored the type under consideration. Prevalence among women and men with 10 or more lifetime partners was 15.4 (95% CI: 5.9–40.2) and 9.5 (95% CI: 4.4–19.8) times higher than among those with 1 partner. Frequent condom use was protective in men, particularly if his partner was HPV-infected (OR = 0.64, 95% CI: 0.50–0.82). This effect was attenuated among women with an infected partner (OR = 0.88, 95% CI: 0.69–1.11). Conclusions: The current partners status was the most important risk factor for prevalent HPV infection. Condoms exerted a stronger protective effect among men than among women.

The influence of academic discourses on medical students' identification with the discipline of family medicine.

Purpose To understand the influence of academic discourses about family medicine on medical students’ professional identity construction during undergraduate training. Method The authors used a multiple case study research design involving international medical schools, one each from Canada, France, Spain, and the United Kingdom (UK). The authors completed the fieldwork between 2007 and 2009 by conducting 18 focus groups (with 132 students) and 67 semistructured interviews with educators and by gathering pertinent institutional documents. They carried out discursive thematic analyses of the verbatim transcripts and then performed within- and cross-case analyses. Results The most striking finding was the diverging responses between those at the UK school and those at the other schools. In the UK case, family medicine was recognized as a prestigious academic discipline; students and faculty praised the knowledge and skills of family physicians, and students more often indicated their intent to pursue family medicine. In the other cases, family medicine was not well regarded by students or faculty. This was expressed overtly or through a paradoxical academic discourse that stressed the importance of family medicine to the health care system while decrying its lack of innovative technology and the large workload-to-income ratio. Students at these schools were less likely to consider family medicine. Conclusions These results stress the influence of academic discourses on medical students’ ability to identify with the practice of family medicine. Educators must consider processes of professional identity formation during undergraduate medical training as they develop and reform medical education.

Improving undergraduate medical education about pain assessment and management: A qualitative descriptive study of stakeholders’ perceptions

BACKGROUND Pain is one of the most common reasons for individuals to seek medical advice, yet it remains poorly managed. One of the main reasons that poor pain management persists is the lack of adequate knowledge and skills of practicing clinicians, which stems from a perceived lack of pain education during the training of undergraduate medical students. OBJECTIVE To identify gaps in knowledge with respect to pain management as perceived by students, patients and educators. METHODS A qualitative descriptive study was conducted. Data were generated through six focus groups with second- and fourth-year medical students, four focus groups with patients and individual semistructured interviews with nine educators. All interviews were audiotaped and an inductive thematic analysis was performed. RESULTS A total of 70 individuals participated in the present study. Five main themes were identified: assessment of physical and psychosocial aspects of pain; clinical management of pain with pharmacology and alternative therapies; communication and the development of a good therapeutic relationship; ethical considerations surrounding pain; and institutional context of medical education about pain. CONCLUSION Participating patients, students and pain experts recognized a need for additional medical education about pain assessment and management. Educational approaches need to teach students to gather appropriate information about pain, to acquire knowledge of a broad spectrum of therapeutic options, to develop a mutual, trusting relationship with patients and to become aware of their own biases and prejudice toward patients with pain. The results of the present study should be used to develop and enhance existing pain curricula content.

Determinants of Human Papillomavirus Coinfections among Montreal University Students: The Influence of Behavioral and Biologic Factors

Background: Human papillomavirus (HPV) coinfections are common among HPV-infected individuals, but the significance and etiology of these infections remain unclear. Though current evidence suggests that women with coinfections have increased HPV exposure (i.e., more sexual partners), it is also hypothesized that these women may represent a subgroup with increased biologic susceptibility. This study sought to examine determinants of coinfections in a cohort of young women, examining both behavioral and biologic factors related to HPV acquisition over time. Methods: Female university students (n = 537) in Montreal, Canada, were followed for 2 years at 6-month intervals. At each visit, cervical specimens were collected for cytology and HPV testing, and women completed a questionnaire about lifestyle and behavior. HLA alleles were typed from purified DNA collected from cervical specimens. Two definitions of coinfections were used: cumulative coinfection over follow-up and concurrent coinfection at each visit. Multiple logistic regression was used to determine predictors of both cumulative and concurrent coinfections using baseline and time-dependent covariates. Results: The most consistent determinant of coinfection occurrence was number of sexual partners, though several genes of the immune response (HLA-DQB1*06:02, HLA-G*01:01:03, and HLA-G*01:01:05) were also identified as significant predictors of cumulative coinfections. Conclusions: HPV coinfections mainly occur due to increased sexual activity, but biologic susceptibility may also be involved in a subset of women. Immunologic factors may put women at greater risk of coinfections over the long term, but short-term risk is almost exclusively driven by modifiable sexual behaviors. Impact: Additional research should continue to further identify immunologic biomarkers of HPV susceptibility. Cancer Epidemiol Biomarkers Prev; 23(5); 812–22. ©2014 AACR.

Estimating HPV DNA Deposition Between Sexual Partners Using HPV Concordance, Y Chromosome DNA Detection, and Self-reported Sexual Behaviors

Background Detection of human papillomavirus (HPV) DNA in genital samples may not always represent true infections but may be depositions from infected sexual partners. We examined whether sexual risk factors and a biomarker (Y chromosome DNA) were associated with genital HPV partner concordance and estimated the fraction of HPV detections potentially attributable to partner deposition. Methods The HITCH study enrolled young women attending a university or college in Montréal, Canada, and their male partners, from 2005 to 2010. We tested baseline genital samples for Y chromosome DNA and HPV DNA using polymerase chain reaction. Results Type-specific HPV concordance was 42.4% in partnerships where at least one partner was HPV DNA positive. Y chromosome DNA predicted type-specific HPV concordance in univariate analyses, but in multivariable models the independent predictors of concordance were days since last vaginal sex (26.5% higher concordance 0-1 vs 8-14 days after last vaginal sex) and condom use (22.6% higher concordance in never vs always users). We estimated that 14.1% (95% confidence interval [CI], 6.3-21.9%) of HPV DNA detections in genital samples were attributable to vaginal sex in the past week. Conclusions A substantial proportion of HPV DNA detections may be depositions due to recent unprotected vaginal sex.