A cross-sectional study of the association of dental health factors with progression and all-cause mortality in men diagnosed with HPV-associated oropharyngeal cancer.

BACKGROUND: Human Papillomavirus-associated oropharyngeal cancer (HPV-OPC) incidence is increasing among men in the United States. Poor dental health has previously been associated with risk of head and neck cancers, oral HPV infection, and persistence but it is not understood whether dental health is associated with outcomes. We sought to determine the association of dental health with progression free survival and overall mortality among men with an HPV-OPC. METHODS: A cross sectional study of men diagnosed with HPV-OPC between 2014-2020 at Moffitt Cancer Center in Tampa, FL was conducted. Dental records were abstracted for assessment of dental fitness prior to cancer treatment. Five dental factors including number of teeth lost, pocket depth, gingival score, loss of attachment, and bone loss were individually examined. Risk factor and outcome data were collected from a patient risk questionnaire and medical record. Using item response theory, an overall dental fitness score from five dental factors was developed in which missing data were multiply imputed. Cox proportional hazards model was used to assess whether dental factors were associated with progression-free survival or overall mortality. RESULTS: Among 206 HPV-OPC cases, median follow-up was 3.4 years (IQR: 2.4-4.4) during which 40 cases involved progression or mortality and 25 deaths occurred. Overall dentition was significantly associated with progression free survival (p = 0.04) and with overall survival (p = 0.03) though findings were not significant after adjustment for age at diagnosis, stage, and smoking history (p = 0.146 and p = 0.120, respectively). A pocket depth of 7 mm or more was associated with overall survival (HR: 5.21; 95% CI: 1.43-19.11) and this remained significant after adjustment for confounding (aHR: 4.14; 95% CI: 1.72-16.26). CONCLUSIONS: Among men diagnosed with an HPV-associated OPC in the US, worse dental health was associated with reduced progression free survival and overall survival, but not after adjustment for confounders. Further studies are needed to examine whether dental health is associated with other prognostic factors and subsequent treatment-related outcomes.

Control of Epstein-Barr Virus (EBV) in the Oral Cavity Is Associated With Persistence of Oral Human Papillomavirus (HPV)16/18 Among Men From the HPV Infection in Men Study.

BACKGROUND: Human papillomavirus (HPV)-related oropharyngeal cancer (OPC) incidence is increasing among men. Biomarkers that can identify oral HPV16/18 infections likely to persist, the obligate precursor for HPV-OPC, are needed. METHODS: We assessed the association between oral Epstein-Barr virus (EBV) and oral HPV16/18 persistence among 63 men in the HPV Infection in Men Study who tested positive for HPV16/18 at the baseline visit. Control of oral coinfections, including EBV, could serve as a biomarker of immune competence and the ability to control oral HPV. RESULTS: Detection of oral EBV was significantly associated with oral HPV16/18 ≥12-month persistence. CONCLUSIONS: Detection of oral EBV deserves evaluation as a biomarker for oral HPV persistence and HPV-related OPC.

Human Papillomavirus 16 Lineage A Variants Associated With Persistent Genital Infections in Men: The HPV Infection in Men (HIM) Study.

BACKGROUND: Human papillomavirus (HPV) 16 non-A lineage variants have higher carcinogenic potential for cervical cancer. HPV-16 variants natural history among males is not established. We evaluated HPV-16 variants prevalence and persistence in the external genitalia of men enrolled in the prospective HPV Infection in Men (HIM) Study. METHODS: The HIM Study included men from the United States, Brazil, and Mexico. HPV-16 variants were distinguished using polymerase chain reaction sequencing. The prevalence of HPV-16 variants was assessed, and associations with infection persistence were estimated. RESULTS: We characterized the HPV-16 variants for 1700 genital swab samples from 753 men and 22 external genital lesions in 17 men. The prevalence of HPV-16 lineages differed by country and marital status (P < .001). Overall, 90.9% of participants harbored lineage A variants. The prevalence of non-A lineages was heterogenous among countries. HPV-16 lineage A variants were associated with a 2.69-fold increased risk of long-term persistent infections compared with non-A lineages. All high-grade penile intraepithelial neoplasia harbored lineage A variants and occurred in the context of long-term persistent infections with the same variants. CONCLUSIONS: The prevalence and persistence of HPV-16 variants observed at the male external genitalia suggest differences in the natural history of these variants between men and women, which may be associated with intrinsic differences in the infected genital epithelia.

The Role of External Genital Lesions in Human Immunodeficiency Virus Seroconversion Among Men Participating in a Multinational Study.

BACKGROUND: Studies in women have shown an increased risk of human immunodeficiency virus (HIV) acquisition with prior human papilloma virus (HPV) infection; however, few studies have been conducted among men. Our objective was to assess whether HPV-related external genital lesions (EGLs) increase risk of HIV seroconversion among men. METHODS: A total of 1379 HIV-negative men aged 18 to 70 years from the United States, Mexico, and Brazil were followed for up to 7 years and underwent clinical examination for EGLs and blood draws every 6 months. Human immunodeficiency virus seroconversion was assessed in archived serum. Cox proportional hazards and marginal structural models assessed the association between EGL status and time to HIV seroconversion. RESULTS: Twenty-nine participants HIV seroconverted during follow-up. Older age was associated with a lower hazard of HIV seroconversion. We found no significant difference in the risk of HIV seroconversion between men with and without EGLs (adjusted hazard ratio, 0.94; 95% confidence interval, 0.32-2.74). Stratified analyses focusing on men that have sex with men found no association between EGLs and HIV seroconversion risk (hazards ratio, 0.63; 95% confidence interval, 0.00-1.86). CONCLUSIONS: External genital lesions were not associated with higher risk for HIV seroconversion in this multinational population, although statistical power was limited as there were few HIV seroconversions. Results may differ in populations at higher risk for HIV.

Differences in Factors Associated With High- and Low-Risk Oral Human Papillomavirus Genotypes in Men.

BACKGROUND: Human papillomavirus (HPV) causes oral warts and oropharyngeal cancer (OPC). Human papillomavirus-attributable OPC incidence among men is significantly increasing worldwide, yet few studies have reported oral HPV across multiple countries or examined factors associated with low- and high-risk HPV separately. METHODS: Oral gargles from 3095 men in the multinational HPV Infection in Men (HIM) Study were HPV genotyped. Multivariable models assessed factors independently associated with high-risk and low-risk HPV prevalence. RESULTS: The prevalence of high-risk and low-risk HPV was 6.0% and 2.8%, respectively. Greater number of sexual partners was only associated with high-risk HPV (1.88; 95% confidence interval [CI], 1.22-2.90) prevalence. In multivariable models, residing in Mexico (1.66; 95% CI, 1.15-2.40) and smoking (1.66; 95% CI, 1.13-2.44) were significantly associated with high-risk HPV, and history of consistent gum bleeding (2.16; 95% CI, 1.35-3.45) was significantly associated with low-risk HPV. Gender of the sexual partner did not alter the results for either high- or low-risk HPV endpoints. CONCLUSIONS: Different factors were independently associated with high- and low-risk oral HPV. Oral sexual behaviors were associated with high-risk HPV, and oral health was associated with low-risk HPV. High-risk HPV prevalence differed by country of residence, highlighting the need for additional studies in multiple countries.

Factors Associated With Persistence and Clearance of High-Risk Oral Human Papillomavirus (HPV) Among Participants in the HPV Infection in Men (HIM) Study.

BACKGROUND: Human papillomavirus (HPV)-attributable oropharyngeal cancer (HPV-OPC) incidence is increasing in many high-income countries among men. Factors associated with oral HPV persistence, the precursor of HPV-OPC, are unknown. Data from the HPV Infection in Men (HIM) Study, which followed participants >7 years, were utilized to examine rates of persistence and associated factors. METHODS: Oral gargle samples from 3095 HIM study participants were HPV genotyped using the SPF10 PCR-DEIA-LiPA25 assay (DDL Diagnostic Laboratory). Oral HPV persistence for individual and grouped high-risk HPV types among 184 men positive for any high-risk HPV at their oral baseline visit was assessed at 6-month intervals. Factors associated with grouped high-risk HPV/HPV16 persistence were examined using logistic regression. Kaplan-Meier curves were constructed to examine median time to HPV clearance overall, and by selected risk factors. RESULTS: Among the 7 HPV vaccine types, HPV33 had the longest median duration (7.6 months) followed by HPV16 and HPV45 (6.4 months). 10-30% of oral high-risk HPV infections persisted ≥24 months. Six months' persistence of oral high-risk HPV infections was positively associated with age and gingivitis and negatively with lifetime number of sexual partners, while 12 months' persistence was only inversely associated with lifetime number of sexual partners. Oral HPV16 persistence was positively associated with baseline HPV16 L1 antibody status. CONCLUSIONS: Eighteen percent of HPV16 infections persisted beyond 24 months, potentially conferring higher risk of HPV-OPC among these men. Older age appears to be an important factor associated with oral high-risk HPV persistence. More studies among healthy men are required to understand the progression of oral HPV infection to HPV-OPC.

Sequential acquisition of human papillomavirus infection between genital and oral anatomic sites in males.

Oral human papillomavirus (HPV) is associated with increasing rates of HPV-associated oropharyngeal cancer (OPC) in men. Sequential infection from one site to another has been demonstrated at the cervix and anus. Thus, risk of an oral HPV infection after a genital infection of the same type in the HPV infection in men study was investigated. Samples from 3140 men enrolled in a longitudinal cohort were assessed for sequential genital to oral infection with one of nine HPV types (HPV 6, 11, 16, 18, 31, 33, 45, 52 and 58); and then also sequential, same-type oral to genital infection. Incidence rate ratios (IRRs) compared rates of oral HPV among men with and without prior genital infection of the same type. Risk of sequential HPV infections were assessed using Cox proportional hazards model. Incidence of an oral HPV infection was significantly higher among men with a prior genital infection of the same type for any of the 9 HPV types (IRR: 2.3; 95% CI: 1.7-3.0). Hazard ratio of a sequential genital to oral HPV infection was 2.3 (95% CI: 1.7-3.1) and 3.5 (95% CI: 1.9-6.4) for oral to genital infection. Both changed minimally after adjustment for age, country, circumcision, alcohol use, lifetime sexual partners and recent oral sex partners. HPV infections at one site could elevate risk of a subsequent genital or oral HPV infection of the same type in men, emphasizing the importance of vaccination to prevent all HPV infections.

Oral human papillomavirus prevalence and type distribution by country (Brazil, Mexico and the United States) and age among HPV infection in men study participants.

Incidence of human papillomavirus (HPV) attributable oropharyngeal cancers (OPCs) has been increasing globally, especially among men in high-income countries. There is a lack of studies comparing oral HPV prevalence by age and country among healthy men. The purpose of our study was to assess oral HPV prevalence by country and age. Participants of the HPV Infection in Men Study (HIM), a cohort of 3,098 healthy men from São Paulo, Brazil, Cuernavaca, Mexico and Tampa, USA, were studied. Oral HPV prevalence and type distribution were assessed using the SPF10 PCR-DEIA-LiPA25 system. The prevalence of any HPV in Brazil, Mexico and the US was 8.7% (95% CI: 7.1%, 10.4%), 10.0% (95% CI: 8.3%, 12.1%) and 7.6% (95% CI: 5.9%, 9.5%), respectively, while the prevalence of high-risk HPV was 5.3% (95% CI: 4.1%, 6.7%), 7.3% (95% CI: 5.7%, 9.0%) and 5.4% (95% CI: 4.0%, 7.0%), respectively. No significant differences in prevalence of grouped HPV types were observed by country despite significant differences in sexual behaviors. However, the age-specific prevalence of oral HPV differed by country. Brazilian (6.0% [95% CI: 3.4%, 9.7%]) and Mexican (9.2% [95% CI: 5.6%, 14.0%]) participants had peak high-risk HPV prevalence among men aged 41-50 years whereas the US participants had peak prevalence at ages 31-40 years (11.0% [95% CI: 6.4%, 17.3%]). In conclusion, oral HPV prevalence was low with no difference in overall prevalence observed by country. Factors associated with the differences in oral HPV age-patterning by country and sexual orientation require further study.

Methylation of HPV 16 and EPB41L3 in oral gargles: Associations with oropharyngeal cancer detection and tumor characteristics.

Oropharyngeal cancer (OPC) incidence is increasing significantly among men and often requires intensive therapy causing significant morbidity. Early detection of OPC is needed, when monotherapy can be safely delivered with less treatment-associated morbidity, while maintaining high cure rates. We conducted a study of 101 pretreatment male OPC cases matched 1:1 to 101 disease-free controls for age and smoking history. Oral gargles were collected from cases and controls with additional biopsies or aspirates from cases. The HPV SPF10 -LiPA25 PCR assay was utilized for HPV genotyping. Methylation of three CpG sites (438, 427 and 425) in the EPB41L3 gene and methylation status of the L1 (6,367, 6,389), L2 (4,257, 4,262, 4,266, 4,269, 4,275, 4,282) and E2 (3,412, 3,415, 3,417, 3,433, 3,436) CpG sites of HPV 16 positive specimens was assessed by pyrosequencing. Significant correlations were observed between tumor and oral specimens for all methylation biomarkers (p < 0.01). EPB41L3 and HPV 16 L1, L2 and E2 methylation were significantly (p < 0.0001) higher among cases than controls, regardless of early vs. late disease. When HPV 16 genes and EPB41L3 methylation status were combined in a logistic regression analysis, a sensitivity of 70.3% and a specificity of 90.9% were observed for the detection of OPC from an oral gargle. Our data suggest that methylation biomarkers measured in oral gargles may have utility in identifying OPC early. Future studies are needed to replicate these findings and to inform additional biomarkers that can maximize specificity and sensitivity for early OPC detection.

Genital Wart Recurrence Among Men Residing in Brazil, Mexico, and the United States.

BACKGROUND: Genital wart (GW) incidence is high among men. The percentage and rate at which subsequent GW events occur are understudied. The purpose of this study was to describe the rate of subsequent GWs, associated human papillomavirus (HPV) types, and time to subsequent GW event among unvaccinated men. METHODS: The study was nested within a multinational prospective HPV natural history study of men aged 18-70 years in the United States, Mexico, and Brazil, examined every 6 months for a median follow-up of 50.4 months. Subsequent GW events were defined as GWs detected after ≥16 weeks of the prior event. RESULTS: Forty-four percent of men experienced ≥1 GW following the initial episode. Men with ≥2 subsequent events were at highest risk of continued GW experiences, with as high as 10 postinitial GW events. The incidence rate of each subsequent GW increased with increasing events (incidence of first subsequent event was 13.1 vs 36.6/1000 person-months for the fourth event). The proportion of GWs among HPV-6 and/or -11-positive patients remained constant across events. Approximately 63%-69% were positive for ≥1 of the 9-valent HPV vaccine types. CONCLUSIONS: These data highlight the high burden of GWs among men across the lifespan and the need for vaccination to prevent multiple GW episodes.

HPV-6 Molecular Variants Association With the Development of Genital Warts in Men: The HIM Study.

Background: Human papillomavirus type 6 (HPV-6) and HPV-11 are the etiological agents of approximately 90% of genital warts (GWs). The impact of HPV-6 genetic heterogeneity on persistence and progression to GWs remains undetermined. Methods: HPV Infection in Men (HIM) Study participants who had HPV-6 genital swabs and/or GWs preceded by a viable normal genital swab were analyzed. Variants characterization was performed by polymerase chain reaction sequencing and samples classified within lineages (A, B) and sublineages (B1, B2, B3, B4, B5). Country- and age-specific analyses were conducted for individual variants; odds ratios and 95% confidence intervals for the risk of GWs according to HPV-6 variants were calculated. Results: B3 variants were most prevalent. HPV-6 variants distribution differed between countries and case status. HPV-6 B1 variants prevalence was increased in GWs and genital swabs of cases compared to controls. There was difference in B1 and B3 variants detection in GW and the preceding genital swab. We observed significant association of HPV-6 B1 variants detection with GW development. Conclusions: HPV-6 B1 variants are more prevalent in genital swabs that precede GW development, and confer an increased risk for GW. Further research is warranted to understand the possible involvement of B1 variants in the progression to clinically relevant lesions.

HPV-11 variability, persistence and progression to genital warts in men: the HIM study.

HPV-11 and HPV-6 are the etiological agents of about 90 % of genital warts (GWs). The intra-typic variability of HPV-11 and its association with infection persistence and GW development remains undetermined. Here, HPV infection in men (HIM) participants who had an HPV-11 genital swab and/or GW, preceded or not by a normal skin genital swab were analysed. Genomic variants were characterized by PCR-sequencing and classified within lineages (A, B) and sublineages (A1, A2, A3, A4). HPV-11 A2 variants were the most frequently detected in the genital swab samples from controls and in both genital swabs and GW samples from cases. The same HPV-11 variant was detected in the GW sample and its preceding genital swab. There was a lack of association between any particular HPV-11 variant and the increased risk for GW development.

Human papillomavirus virus (HPV) genotype- and age-specific analyses of external genital lesions among men in the HPV Infection in Men (HIM) Study.

BACKGROUND: Human papillomavirus (HPV) causes external genital lesions (EGLs) in men, including condyloma and penile intraepithelial neoplasia (PeIN). We sought to determine the incidence of pathologically confirmed EGLs, by lesion type, among men in different age groups and to evaluate the HPV types that were associated with EGL development. METHODS: HPV Infection in Men (HIM) study participants who contributed ≥2 visits from 2009-2013 were included in the biopsy cohort. Genotyping by an HPV line-probe assay was performed on all pathologically confirmed EGLs. Age-specific analyses were conducted for incident EGLs, with Kaplan-Meier estimation of cumulative incidence. RESULTS: This biopsy cohort included 2754 men (median follow-up duration, 12.4 months [interquartile range, 6.9-19.2 months]). EGLs (n = 377) were pathologically confirmed in 228 men, 198 of whom had incident EGLs. The cumulative incidence of any EGL was highest among men <45 years old and, for condyloma, decreased significantly over time with age. The genotype-specific incidence of EGL varied by pathological diagnoses, with high- and low-risk genotypes found in 15.6% and 73.2% of EGLs, respectively. Condyloma primarily contained HPV 6 or 11. While PeIN lesions primarily contained HPV 16, 1 PeIN III lesion was positive for HPV 6 only. CONCLUSION: Low- and high-risk HPV genotypes contribute to the EGL burden. Men remain susceptible to HPV-related EGLs throughout the life span, making it necessary to ensure the longevity of immune protection against the most common causative HPV genotypes.

Role of histological findings and pathologic diagnosis for detection of human papillomavirus infection in men.

Early HPV infection in males is difficult to detect clinically and pathologically. This study assessed histopathology in diagnosing male genital HPV. External genital lesions (n = 352) were biopsied, diagnosed by a dermatopathologist, and HPV genotyped. A subset (n = 167) was diagnosed independently by a second dermatopathologist and also re-evaluated in detail, tabulating the presence of a set of histopathologic characteristics related to HPV infection. Cases that received discrepant diagnoses or HPV-related diagnoses were evaluated by a third dermatopathologist (n = 163). Across dermatopathologists, three-way concordance was fair (k = 0.30). Pairwise concordance for condyloma was fair to good (k = 0.30-0.67) and poor to moderate for penile intraepithelial neoplasia (k = -0.05 to 0.42). Diagnoses were 44-47% sensitive and 65-72% specific for HPV 6/11-containing lesions, and 20-37% sensitive and 98-99% specific for HPV 16/18. Presence of HPV 6/11 was 75-79% sensitive and 35% specific for predicting pathologic diagnosis of condyloma. For diagnosis of penile intraepithelial neoplasia, HPV 16/18 was 95-96% specific but only 40-64% sensitive. Rounded papillomatosis, hypergranulosis, and dilated vessels were significantly (P < 0.05) associated with HPV 6/11. Dysplasia was significantly (P = 0.001) associated with HPV 16/18. Dermatopathologists' diagnoses of early male genital HPV-related lesions appear discordant with low sensitivity, while genotyping may overestimate clinically significant HPV-related disease. Rounded papillomatosis, hypergranulosis, and dilated vessels may help establish diagnosis of early condyloma.

Anal human papillomavirus (HPV) disagreement by Linear Array compared to SPF10 PCR-DEIA-LiPA25 system in young sexual minority men.

Introduction: Young sexual minority men (SMM) bear the greatest burden of anal human papillomavirus (HPV) infections. We assessed anal HPV genotype discordance between the Linear Array (LA) and SPF10 PCR-DEIA-LiPA25 (LiPA25). Methods: Discordance was assessed between LA and LiPA25 using self-collected anal swabs from 120 SMM aged 18-29 who were recruited in 2014-2016. Multiple-type infection was explored as a potential confounder of testing agreement, along with clinical and behavioral factors such as HIV status, syphilis status, incarceration history, health insurance coverage, having 3 or more sex partners in the past 6 months, and co-infection with HPV-16. Results: Significant discordance was found for HPV-6, -11, -16, -31, -42, -54, and -59. Exploratory analyses suggest higher prevalence of genotype discordance in those living with HIV, those with 3 or more sex partners, and those who were positive for 4 or more HPV types. Conclusions: Our results highlight the importance of HPV detection methods which may inform different interpretations of research assessing anal HPV natural history among SMM at highest risk for HPV.

Safety and immunogenicity of a third dose of mRNA-1273 vaccine among cancer patients.

BACKGROUND: Compared to the general population, cancer patients are at higher risk of morbidity and mortality following SARS-CoV-2 infection. The immune response to a two-dose regimen of mRNA vaccines in cancer patients is generally lower than in immunocompetent individuals. Booster doses may meaningfully augment immune response in this population. We conducted an observational study with the primary objective of determining the immunogenicity of vaccine dose three (100 µg) of mRNA-1273 among cancer patients and a secondary objective of evaluating safety at 14 and 28 days. METHODS: The mRNA-1273 vaccine was administered ∼7 to 9 months after administering two vaccine doses (i.e., the primary series). Immune responses (enzyme-linked immunosorbent assay [ELISA]) were assessed 28 days post-dose three. Adverse events were collected at days 14 (± 5) and 28 (+5) post-dose three. Fisher exact or X2 tests were used to compare SARS-CoV-2 antibody positivity rates, and paired t-tests were used to compare SARS-CoV-2 antibody geometric mean titers (GMTs) across different time intervals. RESULTS: Among 284 adults diagnosed with solid tumors or hematologic malignancies, dose three of mRNA-1273 increased the percentage of patients seropositive for SARS-CoV-2 antibody from 81.7% pre-dose three to 94.4% 28 days post-dose three. GMTs increased 19.0-fold (15.8-22.8). Patients with lymphoid cancers or solid tumors had the lowest and highest antibody titers post-dose three, respectively. Antibody responses after dose three were reduced among those who received anti-CD20 antibody treatment, had lower total lymphocyte counts and received anticancer therapy within 3 months. Among patients seronegative for SARS-CoV-2 antibody pre-dose three, 69.2% seroconverted after dose three. A majority (70.4%) experienced mostly mild, transient adverse reactions within 14 days of dose three, whereas severe treatment-emergent events within 28 days were very rare (<2%). CONCLUSION: Dose three of the mRNA-1273 vaccine was well-tolerated and augmented SARS-CoV-2 seropositivity in cancer patients, especially those who did not seroconvert post-dose two or whose GMTs significantly waned post-dose two. Lymphoid cancer patients experienced lower humoral responses to dose three of the mRNA-1273 vaccine, suggesting that timely access to boosters is important for this population.

Oral Human Papillomavirus Prevalence and Genotyping Among a Healthy Adult Population in the US.

Importance: In the US, oropharyngeal cancer, predominantly caused by high-risk (HR) human papillomavirus (HPV) infection, is the most frequent HPV-associated cancer, surpassing cervical cancer. However, little is known about oral HPV prevalence and genotype distribution in the general population. Objective: To assess oral HPV prevalence and factors associated with HR and low-risk infection in a general US population. Design, Setting, and Participants: PROGRESS (Prevalence of Oral HPV Infection, a Global Assessment) was a cross-sectional observational study conducted between November 2021 and March 2022 in 43 dental offices in the US (24 urban, 13 urban cluster, and 6 rural sites), spanning 21 states. Eligible participants were aged 18 to 60 years, visiting dental clinics for routine dental examination. Dental clinics used targeted sampling to recruit equal distributions of men and women and across age groups. Exposure: Participants provided an oral gargle specimen for HPV DNA and genotyping and completed behavioral questionnaires, and dentists reported oral health status. Detection of HPV DNA and genotyping was performed using the SPF10/DEIA/LiPA25 system at a central laboratory. Main Outcome: Oral HPV prevalence. Results: Of the 3196 participants enrolled, mean (SD) age was 39.6 (12.1) years, and 55.5% were women. Oral HPV prevalence was 6.6% (95% CI, 5.7%-7.4%) for any HPV genotype, and 2.0% (95% CI, 1.5%-2.5%), 0.7% (95% CI, 0.4%-1.0%), and 1.5% (95% CI, 1.1%-1.9%) for HR, HPV-16, and 9-valent-HPV vaccine types, respectively. Among HPV-positive participants, HPV-16 was the most prevalent genotype (12.4% among men and 8.6% among women). Prevalence of HPV was higher in men than women and highest among men aged 51 to 60 years (16.8%, 6.8%, and 2.1% for any HPV, HR HPV, and HPV-16, respectively). Factors associated with HR oral infection included being male (adjusted odds ratio [AOR], 3.1; 95% CI, 1.2-8.5), being aged 51 to 60 years (AOR, 3.3; 95% CI, 1.5-7.3), having 26 or more lifetime male sex partners (AOR, 6.5; 95% CI, 2.3-18.7), and having 6 to 25 lifetime female oral sex partners (AOR, 3.4; 95% CI, 1.3-8.7). Conclusions and Relevance: In this cross-sectional study, oral HPV burden was highest among older men who may be at higher risk of developing oropharyngeal cancer. In addition to male sex and older age, HR oral HPV infection was also associated with sexual behaviors, including increasing number of male sex partners and female oral sex partners.

Neutralizing Antibody Response following a Third Dose of the mRNA-1273 Vaccine among Cancer Patients.

Cancer patients are at an increased risk of morbidity and mortality from SARS-CoV-2 infection and have a decreased immune response to vaccination. We conducted a study measuring both the neutralizing and total antibodies in cancer patients following a third dose of the mRNA-1273 COVID-19 vaccine. Immune responses were measured with an enzyme-linked immunosorbent assay (ELISA) and neutralization assays. Kruskal-Wallis tests were used to evaluate the association between patient characteristics and neutralization geometric mean titers (GMTs), and paired t-tests were used to compare the GMTs between different timepoints. Spearman correlation coefficients were calculated to determine the correlation between total antibody and neutralization GMTs. Among 238 adults diagnosed with cancer, a third dose of mRNA-1273 resulted in a 37-fold increase in neutralization GMT 28 days post-vaccination and maintained a 14.6-fold increase at 6 months. Patients with solid tumors or lymphoid cancer had the highest and lowest neutralization GMTs, respectively, at both 28 days and 6 months post-dose 3. While total antibody GMTs in lymphoid patients continued to increase, other cancer types showed decreases in titers between 28 days and 6 months post-dose 3. A strong correlation (p < 0.001) was found between total antibody and neutralization GMTs. The third dose of mRNA-1273 was able to elicit a robust neutralizing antibody response in cancer patients, which remained for 6 months after administration. Lymphoid cancer patients can benefit most from this third dose, as it was shown to continue to increase total antibody GMTs 6 months after vaccination.

Race and prevalence of human papillomavirus infection among men residing in Brazil, Mexico and the United States.

Human papillomavirus (HPV) causes anal, penile and oropharyngeal cancers in men. Genital HPV prevalence in men appears to vary by world region with men residing in Asia having among the lowest prevalence. Unfortunately, there is little information on prevalence of HPV infection in men by race. The purpose of this study was to examine HPV prevalence by race across three countries. 3,909 men ages 18-70 years enrolled in an ongoing prospective cohort study of the natural history of HPV in men (The HIM Study) were included in the analysis. Participants completed risk factor questionnaires and samples were taken from the penile epithelium and scrotum for HPV detection. HPV testing of the combined DNA extract was conducted using PCR and genotyping. Asian/Pacific Islanders had the lowest HPV prevalence of 42.2% compared to Blacks (66.2%), and Whites (71.5%). The Asian/Pacific Islander race was strongly protective in univariate analysis (prevalence ratio (PR) = 0.59; 95% confidence interval (CI): 0.48-0.74) and multivariate analysis for any HPV infection (PR = 0.65; 95% CI: 0.52-0.8). Stratified analysis by lifetime number of female partners also showed strong inverse associations with the Asian/Pacific Islander race. We consistently observed the lowest prevalence of HPV infection among Asian/Pacific Islanders with moderate inverse associations even after various adjustments for potential confounding factors. Unmeasured behavioral factors, sexual mixing with low risk women, and/or race-specific differences in the frequency of germline variations among immune regulating genes may underlie these associations. Further studies among Asian populations that incorporate measures of immuno-genetics are needed to understand this phenomenon.

Methylation of HPV16 and EPB41L3 in oral gargles and the detection of early and late oropharyngeal cancer.

As oropharyngeal cancer (OPC) associated with human papillomavirus (HPV) increases in men, the need for a screening test to diagnose OPC early is crucial. While HPV-associated OPC has a favorable prognosis, recurrence is likely, and metastatic OPC is often incurable regardless of HPV status. Our previous study of pretreatment, male OPC cases (n = 101) and age- and smoking-matched controls (n = 101) found methylation of the host EPB41L3 tumor suppressor gene and HPV16 in the oral gargle was correlated with these biomarkers in the tumor. Methylation of these genes in the oral gargle was significantly (p < 0.0001) higher among cases compared to controls. To further study the utility of HPV16/EPB41L3 methylation, we expanded the sample size and specifically increased the number of early OPC cases (T1-T2, N0-N1; small tumors with a single ipsilateral node <3 cm) to evaluate these biomarkers in early and late OPC. This study included 228 OPC cases, 92 of which were early cases and frequency matched to 142 healthy controls. In logistic regression, the AUC for HPV16/EPB41L3 methylation for all OPC cases was 0.82. Among early and late OPC cases, the AUC was 0.78 and 0.85, respectively. For early cases, 76% sensitivity was achieved, replicating results from our prior study, with a specificity of 65%, indicating room for improvement. The ability of HPV16/EPB41L3 methylation to distinguish OPC from healthy controls highlights its utility as a potential biomarker for OPC. However, the inability to predict early OPC better than late stage OPC indicates the need for additional biomarkers to improve screening performance.