Xerostomia is the most common late toxicity after head and neck radiation. We demonstrate injection of a hydrogel spacer anteriorly displacing the submandibular gland. This procedure enables reduced ...dose to the displaced submandibular gland in cadaveric models of oropharynx cancer treated with IMRT, with potential implications in reducing xerostomia risk.
Human papillomavirus (HPV) is an etiologic agent for both oropharyngeal and cervical cancers, yet little is known about the interrelationship between oral and cervical HPV infections. Therefore, we ...compared the prevalences and type distributions of oral and cervical HPV infections and evaluated infection concordance in a cross-sectional study within the Women's Interagency HIV Study cohort. Oral rinse and cervical-vaginal lavage samples were concurrently collected from a convenience sample of 172 human immunodeficiency virus (HIV)-positive and 86 HIV-negative women. HPV genomic DNA was detected by PGMY09/11 L1 consensus primer PCR and type specified by reverse line blot hybridization for 37 HPV types and β-globin. Only 26 of the 35 HPV types found to infect the cervix were also found within the oral cavity, and the type distribution for oral HPV infections appeared distinct from that for cervical infections (P < 0.001). Oral HPV infections were less common than cervical infections for both HIV-positive (25.2% versus 76.9%, P < 0.001) and HIV-negative (9.0% versus 44.9%, P < 0.001) women. Oral HPV infections were more common among women with a cervical HPV infection than those without a cervical HPV infection (25.5% versus 7.9%, P = 0.002). The majority of women (207; 93.7%) did not have simultaneous oral and cervical infections by the same HPV type; however, the number of women who did (14; 6.3%) was significantly greater than would be expected by chance (P = 0.0002). Therefore, the oral and cervical reservoirs for HPV infection are likely not entirely independent of one another.
Human papillomavirus-related oropharyngeal carcinoma (HPV-OPC) is increasing in incidence in the United States. Although HPV-OPC has favorable prognosis, 10% to 25% of HPV-OPCs recur. Detection of ...human papillomavirus (HPV) DNA in oral rinses is associated with HPV-OPC, but its potential as a prognostic biomarker is unclear.
To determine whether HPV DNA detection in oral rinses after treatment for HPV-OPC is associated with recurrence and survival.
Prospective cohort study of patients with incident HPV-OPC diagnosed from 2009 to 2013 at 4 academic tertiary referral cancer centers in the United States. Oral rinse samples were collected at diagnosis and after treatment (9, 12, 18, and 24 months after diagnosis), and evaluated for HPV DNA. Among an initial cohort of 157 participants with incident HPV-OPC treated with curative intent, 124 had 1 or more posttreatment oral rinses available and were included in this study.
Disease-free survival (DFS) and overall survival (OS) were estimated by the Kaplan-Meier method, and the association of HPV DNA detection in oral rinses with survival was evaluated using Cox regression analysis.
Oral HPV type 16 (HPV16) DNA was common at diagnosis (67 of 124 participants 54%). In contrast, oral HPV16 DNA was detected in only 6 participants after treatment (5%), including 5 with HPV16 DNA also detected at diagnosis (persistent oral HPV16 DNA). Two-year DFS and OS were 92% (95% CI, 94%-100%) and 98% (95% CI, 93%-99%). Persistent oral HPV16 DNA was associated with worse DFS (hazard ratio, 29.7 95% CI, 9.0-98.2) and OS (hazard ratio, 23.5 95% CI, 4.7-116.9). All 5 participants with persistent oral HPV16 DNA developed recurrent disease, 3 with local disease involvement. In contrast, just 9 of 119 participants (8%) without persistent oral HPV16 DNA developed recurrent disease, only 1 (11%) with local disease involvement. Median (range) time from earliest posttreatment oral HPV16 DNA detection to recurrence was 7.0 (3.7-10.9) months.
Human papillomavirus type 16 DNA in oral rinses is common at diagnosis but rare after treatment for HPV-OPC. Our data suggest that, although infrequent, persistent HPV16 DNA in posttreatment oral rinses is associated with poor prognosis and is a potential tool for long-term tumor surveillance, perhaps more so for local recurrence.
OBJECTIVES/GOALS: The effect of immunosuppressive metabolites on anti-tumor immunity in human papillomavirus (HPV)-associated vs carcinogen-driven head and neck cancer is unknown. The objective of ...this study is to define the extent to which metabolites impair this response and identify novel metabolic targets for enhancing anti-tumor immunity. METHODS/STUDY POPULATION: HPV-associated and carcinogen-driven head and neck squamous cell carcinoma specimens were frozen following surgical excision, and tumor sections were cut onto glass slides. Slides were coated in alpha-cyano-4-hydroxy-cinnamic acid (CHCA) matrix and subjected to mass spectrometry imaging using matrix-assisted laser desorption ionization (MALDI) on a Bruker SolariX XR 12T Hybrid QqFT-ICR mass spectrometer run in positive mode. Slides were then stained for immunohistochemistry (IHC) using markers of CD8 T cells, macrophages (CD163), B cells (CD20), and tumor cells (panCK). Mass spectrometry imaging and IHC spatially resolved data will be co-registered and metabolite intensity in regions of interest (cell types) quantified. RESULTS/ANTICIPATED RESULTS: A total of seven HPV-associated (three metastatic lymph nodes and four primary tumors) and six carcinogen-driven (primary tumors) HNSC specimens were subjected to MALDI and IHC. Metabolites significantly enriched in HPV-associated HNSC relative to carcinogen-driven HNSC include 2,3-diphosphoglyceric acid, xanthine, 2,3,5-Trichloromaleylacetate, and indole-3-carboxyaldehyde. Metabolites significantly enriched in carcinogen-driven HNSC relative to HPV-associated HNSC include hesperetin 3'-O-sulfate, hypoxanthine, phosphorylcholine, and L-homocysteine sulfonic acid. In ongoing analyses, we anticipate identifying a relationship between CD8+ T cell enriched vs depleted regions and immunosuppressive metabolites (e.g., kynurenine, adenosine monophosphate). DISCUSSION/SIGNIFICANCE: Defining the extent to which CD8+ T cells interact with the metabolic milieu of the microenvironment will provide a foundation for metabolic Precision Medicine. Strategically targeting metabolic pathways to enhance the anti-tumor immune response will be leveraged for the design and implementation of immune modulatory metabolic therapy.
The incidence of human papillomavirus (HPV)-associated head and neck cancers is rising, particularly among men. Whether observed epidemiological differences in sex are explained by differences in ...sexual exposure and/or by immune response is unclear. In this cross-sectional, multi-institutional study, seroprevalence of antibodies to HPV L1 capsid antigen was compared by patient characteristics among 374 adult patients without cancer. A significantly higher seroprevalence was observed among women compared with men for HPV16 (OR = 2.96, 95% CI = 1.21-7.21) and HPV18 (OR = 2.84, 95% CI = 1.06-7.60) L1 antibodies. This difference persisted for HPV16 after controlling for lifetime and recent sexual behavior. After controlling for sex, HPV16 and HPV18 L1 seroprevalence was also significantly associated with higher number of lifetime (HPV16 OR = 1.05, 95% CI = 1.01-1.08; HPV18 OR = 1.04, 95% CI = 1.01-1.08) and recent (HPV16 OR = 1.54, 95% CI = 1.15-2.07; HPV18 OR = 1.40, 95% CI = 1.07-1.82) oral but not vaginal sexual partners. These findings potentially suggest a more robust immune response to HPV16/18 among women compared with men that may not be explained by differences in number of sexual partners, and thereby presumably HPV exposure. The independent association of HPV16/18 L1 seroprevalence with higher number of oral sexual partners suggests a possible role for site of mucosal exposure in the HPV immune response.
HIV has been shown to increase the likelihood of oral HPV infection. In this study, we evaluated the risk of oral HPV in HIV infected patients compared with HIV-negative controls.
101 healthy adult ...volunteers (HIV-) and 245 adults living with HIV infection (HIV+) were recruited from 5 academic medical centers. Questionnaires and saliva samples were obtained every 3–8 months over a period of 2 years (2015–2017). DNA was isolated from the saliva samples and tested for 18 high- and low-risk genotypes.
Oral HPV was detected in 23% of HIV + vs. 10% of HIV- participants (p < 0.0001). Men had a higher oral HPV prevalence than women (27% vs. 15% HIV+, p = 0.03, 16% vs. 5% HIV-, p = 0.01). Risk factors among HIV + participants included more lifetime deep kissing and oral sex partners, and history of AIDS. Persistent oral HPV was detected in 23% of HIV + vs. 5% of HIV- participants (p < 0.001). Among 8 HIV + participants with CD4 counts <200 cell/μL none had cleared their HPV infection during the study.
Risk of oral HPV infection and persistence was significantly higher in HIV + adults with a history of poorly controlled HIV, which may put them at increased risk of HPV-associated cancer.
Incidence of human papillomavirus (HPV)-related oropharyngeal cancer is increasing. There is interest in identifying healthy individuals most at risk for development of oropharyngeal cancer to inform ...screening strategies.
All data are from 2009 to 2014, including 13 089 people ages 20–69 in the National Health and Nutrition Examination Survey (NHANES), oropharyngeal cancer cases from the Surveillance, Epidemiology, and End Results (SEER 18) registries (representing ∼28% of the US population), and oropharyngeal cancer mortality from National Center for Health Statistics (NCHS). Primary study outcomes are (i) prevalence of oncogenic HPV DNA in an oral rinse and gargle sample, and (ii) incident oropharyngeal squamous cell cancer.
Oncogenic oral HPV DNA is detected in 3.5% of all adults age 20–69 years; however, the lifetime risk of oropharyngeal cancer is low (37 per 10 000). Among men 50–59 years old, 8.1% have an oncogenic oral HPV infection, 2.1% have an oral HPV16 infection, yet only 0.7% will ‘ever’ develop oropharyngeal cancer in their lifetime. Oncogenic oral HPV prevalence was higher in men than women, and increased with number of lifetime oral sexual partners and tobacco use. Men who currently smoked and had ≥5 lifetime oral sexual partners had ‘elevated risk’ (prevalence = 14.9%). Men with only one of these risk factors (i.e. either smoked and had 2–4 partners or did not smoke and had ≥5 partners) had ‘medium risk’ (7.3%). Regardless of what other risk factors participants had, oncogenic oral HPV prevalence was ‘low’ among those with only ≤1 lifetime oral sexual partner (women = 0.7% and men = 1.7%).
Screening based upon oncogenic oral HPV detection would be challenging. Most groups have low oncogenic oral HPV prevalence. In addition to the large numbers of individuals who would need to be screened to identify prevalent oncogenic oral HPV, the lifetime risk of developing oropharyngeal caner among those with infection remains low.
Abstract Purpose The purpose of this study was to determine the incidence of and risk factors for pharyngocutaneous fistula in patients undergoing total laryngectomy at a single institution. ...Materials and methods The records of 59 patients undergoing primary or salvage total laryngectomy at our institution from 2001 to 2012 were retrospectively reviewed. Data collected included patient, tumor and treatment characteristics, and surgical technique. Risk factors were analyzed for association with pharyngocutaneous fistula formation. Results Twenty patients (34%) developed fistulas. Preoperative tracheostomy (OR 4.1; 95% CI 1.3–13 p = 0.02) and low postoperative hemoglobin (OR 9.1; 95% CI 1.1–78 p = 0.04) were associated with fistula development. Regarding surgical technique, primary sutured closure of the total laryngectomy defect had the lowest fistula rate (11%). In comparison, primary stapled closure and pectoralis onlay flap over primary closure had nonsignificantly increased fistula rates (43%, OR 6.0; 95% CI 1.0–37.3 p = 0.06 and 25%, OR 2.7; 95% CI 0.4–23.9 p = 0.38, respectively). Pectoralis flap incorporated into the suture line had a significantly increased fistula rate (50%, OR 7.1; 95% CI 1.4–46 p = 0.02). After stratification for salvage status, patient comorbidities were associated with fistula in non-salvage cases whereas disease-related characteristics were associated with fistula in salvage cases. Fistula development was associated with increased length of hospital stay ( p < 0.001) and increased time before oral diet initiation ( p < 0.001). Conclusions Pharyngocutaneous fistula is a common complication of total laryngectomy. Preoperative tracheostomy, postoperative hemoglobin, and surgical technique are important in determining the risk of fistula.
PDF
