Oncogenic DNA viruses found in salivary gland tumors.

BACKGROUND: Previous investigations studying the association of DNA viruses with salivary gland tumors (SGTs) have led to conflicting results. The aim of this study was to determine the prevalence of different DNA viruses by using a highly sensitive assay in a multi-center series of over 100 fresh frozen salivary gland samples. METHODS: DNA was isolated from 84 SGTs (80 parotid tumors and 4 submandibular gland tumors) and 28 normal salivary tissue samples from 85 patients in Northeast Italy. Using a highly sensitive type-specific multiplex genotyping assay, we analyzed the samples for the presence of DNA from 62 different viruses including 47 papillomaviruses, 10 polyomaviruses, and 5 herpesviruses. RESULTS: We observed a high prevalence of beta human papillomavirus DNA in malignant tumors. In contrast, polyomavirus DNA was present in benign, malignant, and non-tumor control samples. Most striking was the significant distribution of herpesvirus DNA in the SGT samples, in particular the high prevalence of Epstein-Barr type 1 and type 2 DNA in Warthin's tumor samples. CONCLUSION: Our data provides evidence for the presence of DNA viruses in SGTs. Mechanistic studies are needed to further attribute tumor formation to these viruses.

Low prevalence of HPV-driven head and neck squamous cell carcinoma in North-East Italy.

OBJECTIVES: To investigate the frequency of Human papillomavirus (HPV)-driven head and neck squamous cell carcinoma (HNSCC) among patients living in North-East Italy, by assessing HPV-DNA positivity in all tumors and additional markers whenever possible. MATERIAL AND METHODS: HPV types, viral load, viral RNA, HPV16/18 E6 protein and p16INK4a and pRb expression were determined in primary tumor tissues from 247 HNSCC patients. Tumor-specific HPV seropositivity was analyzed in 102 patients. RESULTS: Tumor HPV-DNA prevalence was 8.5% overall (21/247) and 27% in oropharynx (17/63). HPV16 accounted for 95% of all HPV types found. Among HPV-DNA+ tumors, type-concordant HPV E6*I RNA prevalence was 79%. HPV DNA+ RNA+ tumors showed high viral load, up-regulated p16INK4a, down-regulated pRb and presence of HPV16 E6 protein. Eight cases showed tumor-specific HPV seropositivity, all type-concordant with the tumor. Tumors were defined as HPV-driven when positive for HPV-DNA plus 2 additional HPV transformation-related markers. CONCLUSION: Relative prevalence of HPV-driven tumors (14 HPV16, 1 HPV58) was 6% overall and 20% among oropharyngeal cancers. In the oropharynx the HPV-driven group showed a trend for better survival versus the HPV-negative group. The relative prevalence of HPV-driven oropharyngeal cancer is low in North-East Italy as compared to Western and Northern Europe.

Deep neck infections: a study of 365 cases highlighting recommendations for management and treatment.

The aims of this investigation were to review the clinical behavior of deep neck infections (DNIs) treated in our institution in order to identify the predisposing factors of life-threatening complications and propose valuable recommendations for management and treatment. A total of 365 adult patients with DNIs were retrospectively identified. One-hundred and thirty-nine patients (38.1%) underwent surgical drainage. Overall, 226 patients (61.9%) responded effectively to intravenous antimicrobial therapy only. There were 67 patients (18.4%) developing life-threatening complications. Diabetes mellitus (odd ratio 5.43; P < 0.001) and multiple deep neck spaces involvement (odd ratio 4.92; P < 0.001) were the strongest independent predictors of complications. The mortality rate was 0.3%. Airway obstruction and descending mediastinitis are the most troublesome complications of DNIs. In selected patients, a trial of intravenous antibiotic therapy associated with an intensive computed tomography-based wait-and-watch policy may avoid an unnecessary surgical procedure. However, about one-fourth of patients present significant comorbidities, which may negatively affect the course of the infection. In these cases and in patients with large or multiple spaces infections, a more aggressive surgical strategy is mandatory.

Matched survival analysis in patients with locoregionally advanced resectable oropharyngeal carcinoma: platinum-based induction and concurrent chemoradiotherapy versus primary surgical resection.

PURPOSE: The outcome of a prospective case series of 47 patients with newly diagnosed resectable locoregionally advanced oropharyngeal squamous cell carcinoma treated with platinum-based induction-concurrent chemoradiotherapy (IC/CCRT) was compared with the outcome of 47 matched historical control patients treated with surgery and postoperative RT. METHODS AND MATERIALS: A total of 47 control patients with locoregionally advanced oropharyngeal squamous cell carcinoma were identified from review of a prospectively compiled comprehensive computerized head-and-neck cancer database and were matched with a prospective case series of patients undergoing IC/CCRT by disease stage, nodal status, gender, and age (± 5 years). The IC/CCRT regimen consisted of one cycle of induction chemotherapy followed by conventionally fractionated RT to a total dose of 66-70 Gy concomitantly with two cycles of chemotherapy. Each cycle of chemotherapy consisted of cisplatinum, 100 mg/m(2), and a continuous infusion of 5-fluorouracil, 1,000 mg/m(2)/d for 5 days. The survival analysis was performed using Kaplan-Meier estimates. Matched-pair survival was compared using the Cox proportional hazards model. RESULTS: No significant difference was found in the overall survival or progression-free survival rates between the two groups. The matched analysis of survival did not show a statistically significant greater hazard ratio for overall death (hazard ratio, 1.35; 95% confidence interval, 0.65-2.80; p = .415) or progression (hazard ratio, 1.44; 95% confidence interval, 0.72-2.87; p = .301) for patients undergoing IC/CCRT. CONCLUSION: Although the sample size was small and not randomized, this matched-pair comparison between a prospective case series and a historical cohort treated at the same institution showed that the efficacy of IC/CCRT with salvage surgery is as good as primary surgical resection and postoperative RT.

Long-term quality of life after treatment for locally advanced oropharyngeal carcinoma: surgery and postoperative radiotherapy versus concurrent chemoradiation.

The aim of this study was to evaluate the long-term quality of life (QoL) in survivors with oropharyngeal carcinoma (OC) treated with surgery and postoperative radiotherapy (PORT) versus concurrent chemoradiation (CRT) using the European Organization for Research and Treatment of Cancer QoL Questionnaires. The study group consisted of 57 patients. The scores for physical (P=0.043) and social (P=0.036) functioning were significantly more favorable in the chemoradiation group. Surgical patients showed statistically higher problems with fatigue (P=0.047), pain (P=0.027), swallowing (P=0.042), social eating (P=0.038) and social contact (P=0.002). CRT group reported significantly greater problems with teeth (P=0.049), open mouth (P=0.036), dry mouth (P=0.022) and sticky saliva (P=0.044). The global QoL score was higher in CRT group (P=0.027). These results support an organ preservation approach with CRT in patients with advanced OC. However, considering the absence of randomized trial comparing outcomes after surgical versus nonsurgical approaches, severe xerostomia following CRT, the higher postoperative morbidity in the setting of salvage surgery, future prospective clinical trials on greater samples of patients are needed to confirm our conclusions.

HPV-16 E6 L83V variant in squamous cell carcinomas of the upper aerodigestive tract.

PURPOSE: The aim of this prospective case series study was to determine the prevalence of HPV-DNA, analyze the E6 mRNA expression, identify intra-type variation in the E6 oncogene in upper aerodigestive tract (UADT) squamous cell carcinoma (SCC), and correlate the presence of HPV-DNA with several clinical parameters and outcome. METHODS: Frozen samples of UADT-SCC were analyzed for the presence and characterization of HPV-DNA and RNA sequences by means of polymerase chain reaction (PCR), reverse transcriptase-PCR, and direct sequencing of amplified products. RESULTS: HPV-DNA sequences were detected in 10% of the tumors, all of which were typed as HPV-16. Positivity for HPV-16 E6/E7 mRNA was observed in five of the eight HPV-positive tumors (62.5%). The HPV-16 E6 L83V variant was present in five cases. Multivariate analysis identified a history of absence of smoking (P = 0.009) as a predictor of HPV-positive tumor. No significant differences in overall and disease free survival curves were observed between patients with HPV-positive tumors and patients with tumors without detectable HPV-DNA. CONCLUSION: Our findings support the etiological participation of HPV-16 in a subset of UADT-SCCs from patients lacking traditional risk factors. The potential prognostic significance of HPV-16 E6 L83V variant in HPV-16 positive UADT-SCCs should be more extensively investigated.