Genetic signatures of HPV-related and unrelated oropharyngeal carcinoma and their prognostic implications

Source: Clinical Cancer Research 15, 1779, March 1, 200 Author: Jens P. Klussmann et al. Purpose: Patients with human papillomavirus (HPV)-containing oropharyngeal squamous cell carcinomas (OSCC) have a better prognosis than patients with HPV-negative OSCC. This may be attributed to different genetic pathways promoting cancer. Experimental Design: We used comparative genomic hybridization to identify critical genetic changes in 60 selected OSCC, 28 of which were associated with HPV-16 as determined by HPV-specific PCR and fluorescence in situ hybridization analysis and positive p16INK4A immunostaining. The results were correlated with HPV status and clinical data from patients. Results: Two thirds of OSCC harbored gain at 3q26.3-qter irrespective of HPV status. In HPV-negative tumors this alteration was associated with advanced tumor stage (P = 0.013). In comparison with HPV-related OSCC, the HPV-negative tumors harbored: (a) a higher number of chromosomal alterations and amplifications (P = 0.03 and 0.039, respectively); (b) significantly more losses at 3p, 5q, 9p, 15q, and 18q, and gains/amplifications at 11q13 (P = 0.002, 0.03; <0.001, 0.02, 0.004, and 0.001, respectively); and (c) less often 16q losses and Xp gains (P = 0.02 and 0.03). Survival analysis revealed a significantly better disease-free survival for HPV-related OSCC (P = 0.02), whereas chromosome amplification was an unfavorable prognostic indicator for disease-free and overall survival (P = 0.01 and 0.05, respectively). Interestingly, 16q loss, predominantly identified in HPV-related OSCC, was a strong indicator of favorable outcome (overall survival, P = 0.008; disease-free survival, P = 0.01) and none of these patients had a [...]

HPV-16 oncoprotein vaccine protects against head and neck cancer in mice

Source: www.medscape.com Author: staff Immunization with a vaccine that targets the E6 and E7 oncoproteins of human papillomavirus-16 (HPV-16) prevents mice with HPV-16-positive head and neck squamous cell cancers (HNSCCs) from expressing these two oncoproteins by mounting a potent immune response. The vaccine may become part of a treatment regimen, along with surgery, chemotherapy or radiotherapy, in patients with HPV-16-positive HNSCCs, investigators report in the December issue of the Archives of Otolaryngology, Head and Neck Surgery. Dr. John H. Lee and colleagues at the Veterans Administration Medical Center in Iowa City generated an adenoviral recombinant vaccine expressing HPV-16 E6/E7 oncoproteins (adenovirus 5 (Ad5) E6/E7). Mice inoculated with the vaccine "completely cleared E6/E7-expressing tumor cells implanted 2 weeks after immunization." (Dr. Lee is now at the Sanford School of Medicine, University of South Dakota, Sioux Falls.) "A time course of interferon-gamma response showed that E6/E7-specific interferon-gamma production is significantly increased in the first 2 weeks after administration of the vaccine and is substantially maintained for up to 70 days," the investigators report. "At all dosages of vaccine, mice inoculated with Ad5 E6/E7 completely cleared E6/E7-expressing tumor cells implanted 2 weeks after either intratracheal or submucosal inoculation, with significant E6/E7-specific interferon-gamma production," the team reports. "Inoculated mice cleared E6/E7-expressing tumor 70 days after implantation." "In accord with this, our data show that immunization with HPV-16 E6/E7 is an effective method for protecting a host from E6/E7-expressing HNSCCs via generation of a potent immune response," Dr. Lee and colleagues write. "Therapeutic vaccines may [...]

Human Papillomavirus-16 modifies the association between fruit consumption and head and neck squamous cell carcinoma

Source: Cancer Epidemiology Biomarkers & Prevention 17, 3419-3426, December 1, 2008 Author: Mara S. Meyer et al. Human papillomavirus-16 (HPV-16) is a risk factor for head and neck squamous cell carcinoma (HNSCC). HPV-positive cancers have distinct disease cofactors and improved survival following treatment. There is conflicting evidence of a protective association of fruit consumption with HNSCC. As HPV-related disease is clinically distinct, we investigated whether the association between fruit consumption and HNSCC risk was modified by exposure to HPV-16. We studied 270 cases and 493 controls with fruit intake information and known HPV-16 antibody status. Cases were identified at nine Boston-area medical facilities between 1999 and 2003. Controls were randomly selected from the greater population and frequency matched to cases by age, gender, and town of residence. Controlling for age, gender, race, smoking, alcohol, total energy intake, body mass index, and education, the seronegative individuals had a significantly lower risk of HNSCC with increasing total fruit consumption [odds ratio (OR)tertile 2, 0.60; 95% confidence interval (95% CI), 0.38-0.95; ORtertile 3, 0.57; 95% CI, 0.35-0.95] and specifically increasing citrus fruit consumption (ORtertile 2, 0.61; 95% CI, 0.39-0.97; ORtertile 3, 0.59; 95% CI, 0.37-0.96). However, among the seropositive, risk increased with greater fruit consumption (ORtertile 2, 2.27; 95% CI, 0.92-5.58; ORtertile 3, 1.40; 95% CI, 0.55-3.59) and citrus fruit consumption (ORtertile 2, 3.35; 95% CI, 1.36, 8.24; ORtertile 3, 3.15; 95% CI, 1.23-8.08). This interaction was statistically significant (P

2008-12-16T09:32:39-07:00December, 2008|Oral Cancer News|

Does Pretreatment Seropositivity to Human Papillomavirus Have Prognostic Significance for Head and Neck Cancers?

Source: Cancer Epidemiology Biomarkers & Prevention 17, 2087-2096, August 1, 2008 Authors: Elaine M. Smith et al. Background: Human papillomavirus (HPV) is a risk factor for head and neck cancers (HNC), yet HPV-associated tumors have better prognosis than HPV-negative tumors. Methods: We evaluated whether pretreatment presence of antibodies to HPV capsids [virus-like particles (VLP)] or to HPV-16 oncoproteins E6 and E7 was a predictor of HPV-positive HNC and clinical outcomes. Sera from 156 HNC patients were tested for antibodies to HPV-16–derived antigens using ELISA. HPV-16 in tumors was evaluated by PCR and DNA sequencing. Results: HPV-16 antibodies were found in 33% with HPV-16 VLP, 21% with HPV-16 E6, and 21% with E7. HPV-16 was detected in 26% of tumors. There was a strong correlation between detection of HPV-16 tumor DNA and antibodies to HPV-16 E6 or E7 ( = 0.7) but not to HPV-16 VLP ( = 0.4). Multivariate analyses showed significantly better disease-specific survival in seropositive HPV-16 VLP [hazard ratio (HR), 0.4; 95% confidence interval (95% CI), 0.1-0.9], HPV-16 E6 (HR, 0.1; 95% CI, 0.02-0.5), and HPV-16 E7 (HR, 0.3; 95% CI, 0.1-0.9) cases. Less disease recurrence occurred among those with antibodies to both E6 and E7 compared with those negative to both (P = 0.003). There was better disease-specific survival in patients who were E6 positive at baseline and remained positive at follow-up compared with individuals who were E6 negative at both time points (P = 0.03; = 0.9). Conclusions: The presence of antibodies to HPV-16 E6 and [...]

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