The causal role of human papillomaviruses (HPV) in squamous cell carcinogenesis of tonsillar cancers (TSCC) depends on the activity of the viral oncoproteins E6 and E7, leading to inactivation of the cellular tumor suppressor p53 and the retinoblastoma gene product pRb. Because of the negative feedback mechanisms, the pRb inactivation causes an increase of the inhibitor of the cyclin-dependent kinases p16 INK4a . In 39 TSCC specimens, genotyping based on the amplification of HPV DNA was carried out using PCR by applying HPV type-specific oligonucleotides. Subsequently, amplicons were hybridised with fluorescence-labeled complementary probes using the Southern blot technology. For HPV E6/E7 mRNA expression, Northern hybridization and RT-PCR were performed, and for p16 INK4a detection, immunohistochemistry was performed. With 21/39 (53%) HPV-positives, the detection rate is within the range that can be expected in TSCC. The E6/E7 oncogene mRNA was detectable in 11 cases, 10 of which showed positive signals after p16 INK4a staining. Albeit the small study group was investigated, the correlation of the HPV DNA status with the p16 INK4a expression was of statistical significance (p 5 0.02). Kaplan-Meier estimations revealed better survival outcome for patients with HPV-positive tumors with detectable E6/E7 mRNA and p16 INK4a overexpression (p 5 0.02, median observation time 29 months). As mRNA expression tests are not routinely available in many clinical diagnostic laboratories, and based on the high correlation of p16 INK4a staining with HPV E6/E7 mRNA expression, in conclusion we suggest for a deeper exploration for the use of p16 INK4a as a surrogate marker with the potential to impact the standard of care of HPV DNA-positive head and neck carcinomas.Malignant tumors of the upper aerodigestive tract account for $7% of all cancers worldwide, 1 with squamous cell carcinomas (SCCs) constituting the largest portion among the different tumor entities. 2 Even though a majority of SCCs of the head and neck (HNSCC) seems associated to etiologic factors as carcinogenetic substances in tobacco smoke and alcohol, 3 an increase of especially younger patients without reported misuse of these environmental factors in history has been recognized. 4 Therefore, an increase in knowledge of other factors such as the infection with human papillomaviruses (HPV) promoting carcinogenesis in especially the latter patient group gains in importance.Epidemiologic data demonstrate HPV DNA prevalences of about 20-30% concerning all anatomical tumor sites of the head and neck region, 4-6 with the SCC of the Waldeyer's tonsillar (squamous cell carcinogenesis of tonsillar cancers, TSCC) ring showing an HPV DNA-positive rate of up to 60% as particularly predestined for an infection with HPV. 4,5,7 Recent data from Sweden describe HPV DNA infections in tonsillar carcinomas in even up to 85% of the investigated patients. 8 HPV DNA-positive HNSCCs, again with accentuation of those derived from the Waldeyer's tonsillar ring, are considered as being ...

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The impact of smoking on survival in patients with squamous cell carcinoma of the head and neck is well established, despite some conflicting data in the literature. However, data on alterations of smoking habit following cancer diagnosis is sparse. In the present study, the effect of reduction of smoking compared with cessation on the course of disease was studied. Data from 643 patients with HNSCC from the tumor documentation registry of the Department of Otorhinolaryngology, Head and Neck Surgery of the Christian-Albrechts-University Kiel were collected and statistically analyzed, looking at pre- and post-treatment smoking habit and survival. Alteration of smoking at the first diagnosis of HNSCC led to a significantly beneficial effect on survival outcomes compared with continued smoking, without significant differences between reduction and cessation of smoking. Detailed analysis revealed that this effect was solely dependent on patients treated by surgery only. Lifelong non-smokers exhibited a significant survival advantage compared with active and former smokers, with no difference in survival between these last two groups. The positive influence of altered smoking habit following first time diagnosis on disease-specific survival paralleled the negative direct effect of active smoking on therapy, which is predominantly attributed to peritumoral tissue hypoxia leading to impaired efficacy of radiochemotherapy (RCT). In the present study cohort, the positive effect of smoking habit alterations were primarily observed in patients treated by surgery only instead of RCT, possibly due to fewer perioperative complications. These findings indicated that patients should be encouraged to at least minimize smoking following cancer diagnosis. Furthermore, for survival estimates and therapy planning, former smokers should be considered as active smokers.

IntroductionTransoral laser microsurgery (TLM) is an accepted and effective treatment strategy for supraglottic carcinomas. Early supraglottic carcinoma has excellent outcomes independently of the treatment approach. The role of TLM for the treatment of locally advanced tumors is debated. Particularly, the functional outcomes after TLM have to be proven by functional assessment of large cohorts of patients. This study analyzes the oncologic and functional outcomes after TLM for supraglottic carcinomas.Patients and methodsNinety-one patients with pT1-pT4a supraglottic carcinomas treated between January 2002 and December 2012 were analyzed. Distribution of tumors (UICC 2010) was 11 patients with pT1, 31 patients with pT2, 36 patients with pT3, and 13 patients with pT4a tumors. Node status was positive in 40 (43.6%) patients; 61 (67.1%) patients had stage III or IVa disease. Local control and survival were estimated using the Kaplan–Meier method. For the assessment of functional outcomes, the MD Anderson Dysphagia Inventory (MDADI), the Voice Handicap Index-10 (VHI-10), and the performance status scale for head and neck cancer [Performance Status Scale for Head and Neck (PSS-HN)] were used.ResultsThe median age was 62 years (range, 33–88 years). Fourteen (15.4%) patients developed a local or locoregional recurrence. The 5-year local control rate and 5-year ultimate local control rate were 72 and 92%, respectively. The 5-year overall survival rate was 63%. Twelve (13.2%) patients needed temporary tracheostomy. Sixty-eight (74.0%) patients had a nasogastric feeding tube post-operatively. At 1-year post-operative follow-up, only three patients were PEG dependent. The median VHI-10 score was 35, the median MDADI composite score was 80, and the median score of the domain “normalcy of diet” in the PSS-HN was 91.ConclusionThe oncologic outcomes are comparable to the results of open surgery for early and advanced supraglottic carcinomas. Functional swallowing outcome is superior to open surgery and to concomitant chemoradiation. Patients treated with TLM perceive low levels of voice- and swallowing-related quality of life impairment.