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.

SARS-CoV-2 antibody response duration and neutralization following natural infection.

Background: The role of the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) neutralizing antibody response from natural infection and vaccination, and the potential determinants of this response are poorly understood. Characterizing this antibody response and the factors associated with neutralization can help inform future prevention efforts and improve clinical outcomes in those infected. Objectives: The goals of this study were to prospectively evaluate SARS-CoV-2 antibody levels and the neutralizing antibody responses among naturally infected adults and to determine demographic and behavioral factors independently associated with these responses. Methods: Serum was collected from seropositive individuals at baseline, four-weeks, and three-months following their first study visit to be evaluated for antibody levels. Detection of neutralizing antibodies was performed at baseline. Participant demographic and behavioral information was collected via web questionnaire prior to their first visit. Results: At baseline, higher antibody levels were associated with better neutralization capacity, with 83% of participants having detectable neutralizing antibodies. We found an age-dependent effect on antibody level and neutralization capacity with participants over 65 years having significantly higher levels. Ethnicity, heart disease, autoimmune disease, and COVID symptoms were associated with higher antibody levels, but not with increased neutralization capacity. Work environment during the pandemic correlated with increased neutralization capacity, while kidney or liver disease and traveling out of state after February 2020 correlated with decreased neutralization capacity, however neither correlated with antibody levels. Conclusions: Our data show that natural infection by SARS-CoV-2 can induce a humoral response reflected by high antibody levels and neutralization capacity.

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.

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.

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.

SARS-CoV-2 Period Seroprevalence and Related Factors, Hillsborough County, Florida, USA, October 2020-March 2021.

Estimating the actual extent of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic is challenging because virus test positivity data undercount the actual number and proportion of persons infected. SARS-CoV-2 seroprevalence is a marker of past SARS-CoV-2 infection regardless of presence or severity of symptoms and therefore is a robust biomarker of infection period prevalence. We estimated SARS-CoV-2 seroprevalence among residents of Hillsborough County, Florida, USA, to determine factors independently associated with SARS-CoV-2 antibody status overall and among asymptomatic antibody-positive persons. Among 867 participants, SARS-CoV-2 period prevalence (October 2020-March 2021) was 19.5% (asymptomatic seroprevalence was 8%). Seroprevalence was 2-fold higher than reported SARS-CoV-2 virus test positivity. Factors related to social distancing (e.g., essential worker status, not practicing social distancing, contact with a virus-positive person, and length of contact exposure time) were consistently associated with seroprevalence but did not differ by time since suspected or known infection (<6 months vs. >6 months).