Background Oropharyngeal squamous-cell carcinomas caused by human papillomavirus (HPV) are associated with favorable survival, but the independent prognostic significance of tumor HPV status remains unknown. Methods We performed a retrospective analysis of the association between tumor HPV status and survival among patients with stage III or IV oropharyngeal squamous-cell carcinoma who were enrolled in a randomized trial comparing accelerated-fractionation radiotherapy (with acceleration by means of concomitant boost radiotherapy) with standard-fractionation radiotherapy, each combined with cisplatin therapy, in patients with squamous-cell carcinoma of the head and neck. Proportional-hazards models were used to compare the risk of death among patients with HPV-positive cancer and those with HPV-negative cancer. Results The median follow-up period was 4.8 years. The 3-year rate of overall survival was similar in the group receiving accelerated-fractionation radiotherapy and the group receiving standard-fractionation radiotherapy (70.3% vs. 64.3%; P = 0.18; hazard ratio for death with accelerated-fractionation radiotherapy, 0.90; 95% confidence interval [CI], 0.72 to 1.13), as were the rates of high-grade acute and late toxic events. A total of 63.8% of patients with oropharyngeal cancer (206 of 323) had HPV-positive tumors; these patients had better 3-year rates of overall survival (82.4%, vs. 57.1% among patients with HPV-negative tumors; P<0.001 by the log-rank test) and, after adjustment for age, race, tumor and nodal stage, tobacco exposure, and treatment assignment, had a 58% reduction in the risk of death (hazard ratio, 0.42; 95% CI, 0.27 to 0.66). The risk of death significantly increased with each additional packyear of tobacco smoking. Using recursive-partitioning analysis, we classified our patients as having a low, intermediate, or high risk of death on the basis of four factors: HPV status, pack-years of tobacco smoking, tumor stage, and nodal stage. Conclusions Tumor HPV status is a strong and independent prognostic factor for survival among patients with oropharyngeal cancer. (ClinicalTrials.gov number, NCT00047008.)

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Human Papillomavirus and Survival of Patients with Oropharyngeal Cancer

Purpose Recent increases in incidence and survival of oropharyngeal cancers in the United States have been attributed to human papillomavirus (HPV) infection, but empirical evidence is lacking. Patients and Methods HPV status was determined for all 271 oropharyngeal cancers (1984-2004) collected by the three population-based cancer registries in the Surveillance, Epidemiology, and End Results (SEER) Residual Tissue Repositories Program by using polymerase chain reaction and genotyping (Inno-LiPA), HPV16 viral load, and HPV16 mRNA expression. Trends in HPV prevalence across four calendar periods were estimated by using logistic regression. Observed HPV prevalence was reweighted to all oropharyngeal cancers within the cancer registries to account for nonrandom selection and to calculate incidence trends. Survival of HPV-positive and HPV-negative patients was compared by using Kaplan-Meier and multivariable Cox regression analyses. Results HPV prevalence in oropharyngeal cancers significantly increased over ...

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Human Papillomavirus and Rising Oropharyngeal Cancer Incidence in the United States

An overview of the self-organizing map algorithm, on which the papers in this issue are based, is presented in this article.

The Self-Organizing Map

Background The improved prognosis for patients with human papillomavirus (HPV) – positive head and neck squamous cell carcinoma (HNSCC) relative to HPV-negative HNSCC observed in retrospective analyses remains to be confirmed in a prospective clinical trial. Methods We prospectively evaluated the association of tumor HPV status with therapeutic response and survival among 96 patients with stage III or IV HNSCC of the oropharynx or larynx who participated in an Eastern Cooperative Oncology Group (ECOG) phase II trial and who received two cycles of induction chemotherapy with intravenous paclitaxel and carboplatin followed by concomitant weekly intravenous paclitaxel and standard fractionation radiation therapy. The presence or absence of HPV oncogenic types in tumors was determined by multiplex polymerase chain reaction (PCR) and in situ hybridization. Two-year overall and progression-free survival for HPV-positive and HPV-negative patients were estimated by Kaplan – Meier analysis. The relative hazard of mortality and progression for HPV-positive vs HPV-negative patients after adjustment for age, ECOG performance status, stage, and other covariables was estimated by use of a multivariable Cox proportional hazards model. All statistical tests were two-sided. Results Genomic DNA of oncogenic HPV types 16, 33, or 35 was located within tumor cell nuclei of 40% (95% confidence interval [CI] = 30% to 50%) of patients with HNSCC of the oropharynx or larynx by in situ hybridization and PCR. Compared with patients with HPV-negative tumors, patients with HPV-positive tumors had higher response rates after induction chemotherapy (82% vs 55%, difference = 27%, 95% CI = 9.3% to 44.7%, P = .01) and after chemoradiation treatment (84% vs 57%, difference = 27%, 95% CI = 9.7% to 44.3%, P = .007). After a median follow-up of 39.1 months, patients with HPV-positive tumors had improved overall survival (2-year overall survival = 95% [95% CI = 87% to 100%] vs 62% [95% CI = 49% to 74%], difference = 33%, 95% CI = 18.6% to 47.4%, P = .005, log-rank test) and, after adjustment for age, tumor stage, and ECOG performance status, lower risks of progression (hazard ratio [HR] = 0.27, 95% CI = 0.10 to 0.75), and death from any cause (HR = 0.36, 95% CI = 0.15 to 0.85) than those with HPV-negative tumors. Conclusion For patients with HNSCC of the oropharynx, tumor HPV status is strongly associated with therapeutic response and survival.

Improved Survival of Patients With Human Papillomavirus–Positive Head and Neck Squamous Cell Carcinoma in a Prospective Clinical Trial

Epstein-Barr virus.

Survival of head and neck cancer (HNC) patients has not dramatically improved over the last 30 years, despite the advances in surgical techniques, chemotherapeutic agents and radiotherapy treatment planning and definition. Different studies in molecular biology of HNC have been carried out, providing useful results for clinical application. HNC usually includes malignant tumors arising from mucosa of the upper aerodigestive tract, from nasopharynx to larynx/trachea, while salivary gland and thyroid cancers are less frequently listed in this classification. In this review, we chose to provide a comprehensive review of the role of biological agents in head and neck subsites. Molecular characteristics and treatment-relevant signaling pathways will be briefly discussed along with the results of the more recent clinical studies that include biological agents.

Biological agents in head and neck cancer

e17530Background: Immunotherapy (IT) provides advantages in a small proportion of recurrent / metastatic head and neck squamous cell carcinoma (RM HNSCC) patients (pts). Predictive biomarkers are s...

Clinical prognostic factors in patients with recurrent or metastatic carcinoma of the head and neck treated with immune checkpoints therapies.

Background

Human papilloma virus oral infection can be related to several factors including HIV infection, cigarette smoking, marijuana consumption and number of sexual partners. We conducted a study on oral HPV prevalence and clearance among the hosts of the San Patrignano community, a population considered at “high-risk” for HPV due to their previous habits.



Methods

From March 2007 to September 2010 all subjects were submitted to oropharyngeal brushing and saliva collection at baseline, after 6, 12 and 48 months (for subjects HPV positive at baseline). Samples were analyzed to detect HPV DNA and virus genotypes. The correlation between HPV prevalence and demographic, behavioral or immunological characteristics was assessed.



Results

Among 194 subjects, 30 (15%) were HPV positive with 25 (13%) high-risk (HR)-HPV at baseline brushing. At 12 months HPV infection was cleared in all cases. However at 48 months HPV was newly detected in 33% of subjects. A correlation between time spent in the community and increase in the ratio of “low-risk” (LR) HPV and HR-HPV was observed. HPV infection was not associated with age, gender, HIV status, HCV, alcohol and/or drug exposure, number of years spent in community, sex with drug-addicts and condom use. Only AIDS under antiretroviral treatment was inversely correlated with the risk of infection.



Conclusions

At 1 year a complete HPV clearance was observed which could be related to adoption of healthier lifestyles of participants. New HPV infections were detected even in the absence of the recognized and declared risky behavioral factors, suggesting a re-expression from a latent infection.

Oral prevalence and clearance of oncogenic human papilloma virus in a rehabilitation community for substance abusers in Italy: a case of behavioral correction?

Biological agents in head and neck cancer.

6046 Background: Recent meta-analysis showed better event free survival in LANPC with induction CT. In head and neck cancer, docetaxel, cisplatin and 5 FU (TPF) induction chemotherapy led to survival gain over cisplatin and 5FU alone. We studied feasibility and activity of TPF induction CT followed by cCTRT in LANPC. Methods: From October 2004 to May 2008, 45 pts with LANPC were treated at our Institution with 2 to 4 cycles (median 3) of induction TPF (docetaxel 75 mg/sm and cisplatin 75 mg/sm on day 1, and 5-FU 750 mg/sm/day ci for 96 hrs. Prophylactic ciprofloxacin was administered for 10 days each cycle, while use of G-CSF was not allowed. Following CT, pts received full doses radiotherapy (RT) concurrent with cisplatin 100 mg/sm q 21 days. Intensity modulated radiotherapy (IMRT) was delivered to 34 pts (76%). All but two pts had non-keratinizing carcinoma. Stage IV pts were 60%, stage III 34%, and 6% stage II. T4 was present in 24% and N3 disease was diagnosed in 42% of the pts. Results: TPF was well ...

Laura D. Locati

Papers

Biological agents in head and neck cancer

Clinical prognostic factors in patients with recurrent or metastatic carcinoma of the head and neck treated with immune checkpoints therapies.

Oral prevalence and clearance of oncogenic human papilloma virus in a rehabilitation community for substance abusers in Italy: a case of behavioral correction?

Biological agents in head and neck cancer.

TPF induction chemotherapy (CT) followed by concomitant cisplatin/radiotherapy (cCTRT) in locally advanced nasopharyngeal cancer (LANPC)