Browsing by Subject "Papillomaviridae"
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Item Open Access Association of tumor necrosis factor-alpha promoter variants with risk of HPV-associated oral squamous cell carcinoma.(Molecular cancer, 2013-07-19) Jin, Lei; Sturgis, Erich M; Zhang, Yang; Huang, Zhigang; Song, Xicheng; Li, Chao; Wei, Qingyi; Li, GuojunTumor necrosis factor alpha (TNF-α) plays an important role in inflammation, immunity, and defense against infection and clearance of human papillomavirus (HPV). Thus, genetic variants may modulate individual susceptibility to HPV-associated oral squamous cell carcinoma (OSCC).In this study we genotyped four common single nucleotide polymorphisms (SNPs) in the TNF-α promoter [ -308G > A(rs1800629), -857C > T (rs1799724), -863C > A (rs1800630), and -1031T > C (rs1799964)] and determined HPV16 serology in 325 OSCC cases and 335 matched controls and tumor HPV status in 176 squamous cell carcinomas of the oropharynx (SCCOP) patients. Univariate and multivariable logistic regression models were used to calculate odds ratios (ORs) and 95% confidence intervals (CIs).We found that HPV16 seropositivity alone was associated with an increased risk of OSCC (OR, 3.1; 95% CI, 2.1-4.6), and such risk of HPV16-associated OSCC was modified by each SNP. Patients with both HPV16 seropositivity and variant genotypes for each SNP had the highest risk when using patients with HPV16 seronegativity and a wild-type genotype as a comparison group. Moreover, similar results were observed for the combined risk genotypes of four variants and all such significant associations were more pronounced in several subgroups, particularly in SCCOP patients and never smokers. Notably, the combined risk genotypes of four variants were also significantly associated with tumor HPV-positive SCCOP.Taken together, these results suggest that TNF-α SNPs may individually or, more likely, jointly affect individual susceptibility to HPV16-associated OSCC, particularly SCCOP and never smokers. Validation of our findings is warranted.Item Open Access Epigenome-wide methylation and progression to high-grade cervical intraepithelial neoplasia (CIN2+): a prospective cohort study in the United States.(BMC cancer, 2023-11) Bukowski, Alexandra; Hoyo, Cathrine; Vielot, Nadja A; Graff, Misa; Kosorok, Michael R; Brewster, Wendy R; Maguire, Rachel L; Murphy, Susan K; Nedjai, Belinda; Ladoukakis, Efthymios; North, Kari E; Smith, Jennifer SBackground
Methylation levels may be associated with and serve as markers to predict risk of progression of precancerous cervical lesions. We conducted an epigenome-wide association study (EWAS) of CpG methylation and progression to high-grade cervical intraepithelial neoplasia (CIN2 +) following an abnormal screening test.Methods
A prospective US cohort of 289 colposcopy patients with normal or CIN1 enrollment histology was assessed. Baseline cervical sample DNA was analyzed using Illumina HumanMethylation 450K (n = 76) or EPIC 850K (n = 213) arrays. Participants returned at provider-recommended intervals and were followed up to 5 years via medical records. We assessed continuous CpG M values for 9 cervical cancer-associated genes and time-to-progression to CIN2+. We estimated CpG-specific time-to-event ratios (TTER) and hazard ratios using adjusted, interval-censored Weibull accelerated failure time models. We also conducted an exploratory EWAS to identify novel CpGs with false discovery rate (FDR) < 0.05.Results
At enrollment, median age was 29.2 years; 64.0% were high-risk HPV-positive, and 54.3% were non-white. During follow-up (median 24.4 months), 15 participants progressed to CIN2+. Greater methylation levels were associated with a shorter time-to-CIN2+ for CADM1 cg03505501 (TTER = 0.28; 95%CI 0.12, 0.63; FDR = 0.03) and RARB Cluster 1 (TTER = 0.46; 95% CI 0.29, 0.71; FDR = 0.01). There was evidence of similar trends for DAPK1 cg14286732, PAX1 cg07213060, and PAX1 Cluster 1. The EWAS detected 336 novel progression-associated CpGs, including those located in CpG islands associated with genes FGF22, TOX, COL18A1, GPM6A, XAB2, TIMP2, GSPT1, NR4A2, and APBB1IP.Conclusions
Using prospective time-to-event data, we detected associations between CADM1-, DAPK1-, PAX1-, and RARB-related CpGs and cervical disease progression, and we identified novel progression-associated CpGs.Impact
Methylation levels at novel CpG sites may help identify individuals with ≤CIN1 histology at higher risk of progression to CIN2+ and inform risk-based cervical cancer screening guidelines.Item Open Access HPV genotypes and cervical intraepithelial neoplasia in a multiethnic cohort in the southeastern USA.(Cancer causes & control : CCC, 2014-08) Vidal, Adriana C; Smith, Jennifer S; Valea, Fidel; Bentley, Rex; Gradison, Maggie; Yarnall, Kimberly SH; Ford, Anne; Overcash, Francine; Grant, Kathy; Murphy, Susan K; Hoyo, CathrinePurpose
For poorly understood reasons, invasive cervical cancer (ICC) incidence and mortality rates are higher in women of African descent. Oncogenic human papillomavirus (HPV) genotypes distribution may vary between European American (EA) and African-American (AA) women and may contribute to differences in ICC incidence. The current study aimed at disentangling differences in HPV distribution among AA and EA women.Methods
Five-hundred and seventy-two women were enrolled at the time of colposcopic evaluation following an abnormal liquid-based cytology screen. HPV infections were detected using HPV linear array, and chi-squared tests and linear regression models were used to compare HPV genotypes across racial/ethnic groups by CIN status.Results
Of the 572 participants, 494 (86 %) had detectable HPV; 245 (43 %) had no CIN lesion, 239 (42 %) had CIN1, and 88 (15 %) had CIN2/3. Seventy-three percent of all women were infected with multiple HPV genotypes. After adjusting for race, age, parity, income, oral contraception use, and current smoking, AAs were two times less likely to harbor HPV 16/18 (OR 0.48, 95 % CI 0.21-0.94, p = 0.03) when all women were considered. This association remained unchanged when only women with CIN2/3 lesions were examined (OR 0.22, 95 % CI 0.05-0.95, p = 0.04). The most frequent high-risk HPV genotypes detected among EAs were 16, 18, 56, 39, and 66, while HPV genotypes 33, 35, 45, 58, and 68 were the most frequent ones detected in AAs.Conclusions
Our data suggest that while HPV 16/18 are the most common genotypes among EA women with CIN, AAs may harbor different genotypes.Item Open Access Human Papillomavirus Awareness in Haiti: Preparing for a National HPV Vaccination Program.(J Pediatr Adolesc Gynecol, 2017-02) Boggan, J; Gichane, MW; Calo, WM; McCarthy, SH; Walmer, KA; Brewer, NTSTUDY OBJECTIVE: Cervical cancer morbidity and mortality are pressing public health issues that affect women in Haiti. To inform efforts to develop a human papillomavirus (HPV) vaccination program in Haiti, we sought to understand HPV awareness and willingness to get HPV vaccination in Haiti. DESIGN, SETTING, AND PARTICIPANTS: We interviewed a convenience sample of 475 women and men in 2 clinical settings in Port-au-Prince and Léogâne, Haiti between April and July 2014. INTERVENTIONS AND MAIN OUTCOME MEASURES: HPV awareness and willingness to get HPV vaccine for daughters. RESULTS: Few participants (27%, 130/475) had heard of HPV. Awareness of HPV was higher among respondents with a previous sexually transmitted infection compared with those without a previous sexually transmitted infection (odds ratio, 2.38; 95% confidence interval, 1.10-5.13). Adults who had heard of genital warts were also more likely to be aware of HPV compared with those who had not (odds ratio, 4.37; 95% confidence interval, 2.59-7.38). Only 10% (24/250) of parents had previously heard of HPV vaccine; however, after researchers explained the purpose of the vaccine, nearly all (96%, 240/250) said they would be willing to get HPV vaccine for their daughters if it were available. CONCLUSION: Despite low awareness of HPV in Haiti, interest in HPV vaccination was nearly universal in our study of health care-seeking adults. This high acceptability suggests that HPV vaccination programs instituted in Haiti would be well received.Item Open Access Interspecies Papillomavirus Type Infection and a Novel Papillomavirus Type in Red Ruffed Lemurs (Varecia rubra).(Viruses, 2023-12) Paietta, Elise N; Kraberger, Simona; Regney, Melanie; Custer, Joy M; Ehmke, Erin; Yoder, Anne D; Varsani, ArvindThe Papillomaviridae are a family of vertebrate-infecting viruses of oncogenic potential generally thought to be host species- and tissue-specific. Despite their phylogenetic relatedness to humans, there is a scarcity of data on papillomaviruses (PVs) in speciose non-human primate lineages, particularly the lemuriform primates. Varecia variegata (black-and-white ruffed lemurs) and Varecia rubra (red ruffed lemurs), two closely related species comprising the Varecia genus, are critically endangered with large global captive populations. Varecia variegata papillomavirus (VavPV) types -1 and -2, the first PVs in lemurs with a fully identified genome, were previously characterized from captive V. variegata saliva. To build upon this discovery, saliva samples were collected from captive V. rubra with the following aims: (1) to identify PVs shared between V. variegata and V. rubra and (2) to characterize novel PVs in V. rubra to better understand PV diversity in the lemuriform primates. Three complete PV genomes were determined from V. rubra samples. Two of these PV genomes share 98% L1 nucleotide identity with VavPV2, denoting interspecies infection of V. rubra by VavPV2. This work represents the first reported case of interspecies PV infection amongst the strepsirrhine primates. The third PV genome shares <68% L1 nucleotide identity with that of all PVs. Thus, it represents a new PV species and has been named Varecia rubra papillomavirus 1 (VarPV1). VavPV1, VavPV2, and VarPV1 form a new clade within the Papillomaviridae family, likely representing a novel genus. Future work diversifying sample collection (i.e., lemur host species from multiple genera, sample type, geographic location, and wild populations) is likely to uncover a world of diverse lemur PVs.Item Open Access Vaginal Self-Sampling for Human Papillomavirus Infection as a Primary Cervical Cancer Screening Tool in a Haitian Population.(Sex Transm Dis, 2015-11) Boggan, Joel C; Walmer, David K; Henderson, Gregory; Chakhtoura, Nahida; McCarthy, Schatzi H; Beauvais, Harry J; Smith, Jennifer SBACKGROUND: Human papillomavirus (HPV) testing as primary cervical cancer screening has not been studied in Caribbean women. We tested vaginal self-collection versus physician cervical sampling in a population of Haitian women. METHODS: Participants were screened for high-risk HPV with self-performed vaginal and clinician-collected cervical samples using Hybrid Capture 2 assays (Qiagen, Gaithersburg, MD). Women positive by either method then underwent colposcopy with biopsy of all visible lesions. Sensitivity and positive predictive value were calculated for each sample method compared with biopsy results, with κ statistics performed for agreement. McNemar tests were performed for differences in sensitivity at ≥cervical intraepithelial neoplasia (CIN)-I and ≥CIN-II. RESULTS: Of 1845 women screened, 446 (24.3%) were HPV positive by either method, including 105 (5.7%) only by vaginal swab and 53 (2.9%) only by cervical swab. Vaginal and cervical samples were 91.4% concordant (κ = 0.73 [95% confidence interval, 0.69-0.77], P < 0.001). Overall, 133 HPV-positive women (29.9%) had CIN-I, whereas 32 (7.2%) had ≥CIN-II. The sensitivity of vaginal swabs was similar to cervical swabs for detecting ≥CIN-I (89.1% vs. 87.9%, respectively; P = 0.75) lesions and ≥CIN-II disease (87.5% vs. 96.9%, P = 0.18). Eighteen of 19 cases of CIN-III and invasive cancer were found by both methods. CONCLUSIONS: Human papillomavirus screening via self-collected vaginal swabs or physician-collected cervical swabs are feasible options in this Haitian population. The agreement between cervical and vaginal samples was high, suggesting that vaginal sample-only algorithms for screening could be effective for improving screening rates in this underscreened population.