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

Mahmud, Salaheddin M.; Robinson, Keira; Richardson, Harriet; Tellier, Pierre-Paul; Ferenczy, Alex; Roger, Michel; Coutlée, François; Franco, Eduardo L.

doi:10.1086/518612

Cited by 34 publications

(37 citation statements)

References 24 publications

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“…17 Cohort studies in Brazil and Canada showed inconsistent findings for the association between HLA class II genes and persistent infection. 19,20 In these studies, the average age of participants was 20 to 30 years. The findings in this study suggest that DRB1*0403 and DRB1*0405 are respectively associated with the high viral load at study entry and persistent infection of HPV18.…”

Section: Discussionmentioning

confidence: 99%

“…19 However, a Canadian cohort study of female university students found no associations between specific HLA class II alleles and risk of HPV persistence. 20 Neither study examined the HLA profiles among persistent infection of specific HPV type. Therefore, different prevalence of HPV types and genetic diversity of study participants might confound the findings.…”

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confidence: 99%

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Associations of human leukocyte antigen class II genotypes with human papillomavirus 18 infection and cervical intraepithelial neoplasia risk

Chuang

Chen

et al. 2011

Cancer

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BACKGROUND: Only a small proportion of women infected with human papillomavirus type 18 (HPV18) may progress to persistent infection and cervical neoplasia. This community-based cohort study aimed to assess associations with human leukocyte antigen (HLA) class II genotypes for natural infection of HPV18 and subsequent risk of cervical neoplasia. METHODS: Among 10,190 cytologically normal participants, 125 with HPV18 infection were identified by HPV blot kit. HPV18 viral load at study entry was examined by real-time polymerase chain reaction; persistent infection was defined as HPV18 infection at 2 consecutive examinations. RESULTS: There was a significant association between HLA-DRB1*0403 allele and high HPV18 viral load (>1000 copies in 50 ng of total DNA) at study entry (odds ratio [OR], 7.2; 95% confidence interval [CI], 2.0-25.2). After adjustment for age and viral load at study entry, haplotype HLA-DRB1*0405-DQA1*0301-DQB1*0302 was significantly associated with persistent HPV18 infection (OR, 13.3; 95% CI, 1.7-105.9). HLA-DRB1*0403 allele was also associated with a significantly increased risk of high-grade squamous intraepithelial lesion or cancer, showing a multivariate-adjusted hazard ratio (95% CI) of 18.1 (2.6-128.5). CONCLUSIONS: HLA-DRB1*0403 allele and HLA-DRB1*0405-DQA1*0301-DQB1*0302 haplotype may play important roles in determination of high viral load and persistent infection of HPV18 and subsequent cervical neoplasia risk.

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Section: Discussionmentioning

confidence: 99%

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confidence: 99%

Associations of human leukocyte antigen class II genotypes with human papillomavirus 18 infection and cervical intraepithelial neoplasia risk

Chuang

Chen

et al. 2011

Cancer

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“…For the sake of analytic efficiency we restricted HLA genotyping to women who met one of two conditions: (i) women who participated in the study for at least 3 visits, or (ii) women who had a persistent infection with the same HPV type for 2 consecutive visits (27). HLA alleles were typed from purified DNA obtained from cervical specimens collected at enrollment, using PCR amplification of sequence-specific primers for HLA-B (27,28).…”

Section: Hla Genotypingmentioning

confidence: 99%

“…HLA alleles were typed from purified DNA obtained from cervical specimens collected at enrollment, using PCR amplification of sequence-specific primers for HLA-B (27,28). These HLA types were chosen a priori based on consistent published evidence to support their role in susceptibility to both HPV infection (27)(28)(29)(30) and cervical cancer (24,26,31,32).…”

Section: Hla Genotypingmentioning

confidence: 99%

“…Through their role in antigen presentation, HLA molecules are thought to be critically involved in cell-mediated immune recognition and viral clearance (25,26), and as such, there is strong biologic plausibility for the HLA system to be involved in the acquisition of HPV coinfections. Indeed, although HLA alleles have been implicated in HPV acquisition (27)(28)(29), persistence (28,30), and carcinogenic progression (24,26,31,32), no studies to date have looked at the impact of specific HLA alleles on the risk of developing HPV coinfections.…”

Section: Introductionmentioning

confidence: 99%

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

Smith

Tellier

Roger

et al. 2014

Cancer Epidemiology, Biomarkers &Amp; Prevention

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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 ¼ 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

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Cervical cancer in Indian women reveals contrasting association among common sub-family of HLA class I alleles

et al. 2014

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We studied the relationship between human leukocyte antigen (HLA) class I alleles and cervical cancer among Indian women. Seventy-five cervical cancer cases were compared with 175 noncancer controls. Cervical biopsy tissue specimen from cancer cases and cervical swab specimen from controls were collected for HPV detection and typing. Blood was taken for HLA typing by PCR-SSOP method. The impact of HLA class I alleles on cervical cancer risk was evaluated using StatCalc program (Epi Info version 6.0.4. CDC Atlanta, GA, USA), and confirmed with Bonferroni correction. Results revealed HLA-B*37, HLA-B*58 were associated significantly with increased risk while HLA-B*40 with decreased risk for cervical cancer. At high-resolution analysis after Bonferroni correction, HLA-B*37:01 allele was associated with increased risk, whereas HLA-B*40:06 was with decreased risk for cervical cancer. HLA-B*37:01 and HLA-B*40:06 belong to the same superfamily of HLA-B44. In silico analysis revealed different binding affinities of HLA-B*37:01 and HLA-B*40:06 for the epitopes predicted for E6 and L1 proteins of HPV16. The higher binding affinity of epitopes to B*40:06, as revealed by docking studies, supports the hypothesis that this allele is able to present the antigenic peptides more efficiently than B*37:01 and thereby can protect the carriers from the risk of cervical cancer. Thus, there is a clear indication that HLA plays an important role in the development of cervical cancer in HPV-infected women. Identification of these factors in high-risk HPV-infected women may help in reducing the cervical cancer burden in India.

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

Abstract: The results of this study support the hypothesis that certain HLA class II polymorphisms mediate genetic susceptibility to the acquisition of HPV infection.

Cited by 34 publications

References 24 publications

Associations of human leukocyte antigen class II genotypes with human papillomavirus 18 infection and cervical intraepithelial neoplasia risk

Associations of human leukocyte antigen class II genotypes with human papillomavirus 18 infection and cervical intraepithelial neoplasia risk

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

Cervical cancer in Indian women reveals contrasting association among common sub-family of HLA class I alleles

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