The inactivation of the tumor suppressor gene p16 plays an important role in the development of malignant tumors. p16 loss can result from point mutations, loss of heterozygosity (LOH) or methylation of the promoter region. A total of 67 samples of tumor tissue from squamous cell carcinoma of the oral cavity, the pharynx and the larynx were analyzed for an inactivation of p16. The results of the molecular-biological investigations were correlated with the known clinical prognostic parameters after a follow-up period of approximately 3 years. Methylation of the promoter region and LOH were the main mechanisms of p16 inactivation. Point mutations presented as rare events. An inactivation of p16 did not have any statistical influence on tumor prognosis. Patients with a p16 gene inactivated by promoter methylation appeared to have a slightly lower tendency for local and regional recurrences. The inactivation of the tumor suppressor gene p16 plays a role in the carcinogenesis of head and neck cancer.

The p16INK4A (CDKN2A/MTS1) putative tumor suppressor gene encodes a cyclin dependent kinase inhibitor which plays an important role in the regulation of the G1/S phase cell cycle checkpoint. A high frequency of various p16 gene alterations were consequently observed in many primary tumors. P16 can be inactivated by different mechanisms: i) homozygous deletion, ii) methylation of the promoter region or iii) point mutation. In order to investigate p16 alterations in head and neck cancer (HNC) we analyzed 70 primary tumors of the larynx, pharynx and oral cavity including their corresponding normal mucosa for mutation inactivation by direct sequencing exon 2. We detected only one so far undescribed transversion G to T at position 322 (Asp108Tyr) and a known polymorphism (Ala148Thr) in five cases. The methylation status of the p16 promoter region was analyzed by an improved highly sensitive methylation-specific PCR protocol. P16 methylation inactivation was found in 16 of 55 cases (29%). Our data indicate that p16 point mutations in HNC are less frequent, but inactivation by methylation of the promoter region could be involved in genesis and progression of HNC.

Fiberoptic tracheo-bronchoscopy is the most commonly used procedure for percutaneous dilational tracheotomy (PDT). However, PDT can be associated with major complications, including death. Furthermore it is unclear, whether the tracheal ring fractures may contribute to the development of tracheal stenosis after PDT nor whether tracheal ring fractures can be prevented by using a rigid endoscope for this procedure. The purpose of this study was to evaluate the feasibility of and the incidence of complications for PDT using the rigid tracheotomy endoscope (TED). In a prospective multicenter observational study from 2006 to 2010, 180 adult patients in intensive care and those scheduled for ear, nose and throat surgery underwent PDT using TED. Data collection was performed using a structured protocol. The patients were observed according to PDT phase (phase 1: puncture, phase 2: dilatation and phase 3: cannula insertion). The descriptive data are given as the number (percent) of cases and the mean ± standard deviation (SD) where appropriate. The relationships between dichotomous and categorical parameters were analyzed using the chi-square test. P values ≤ 0.05 were considered significant. PDT was performed in 179 patients. The procedure time was 14.8 ± 6.2 (mean ± SD) minutes. Pneumothorax or procedure-related lethal complications did not occur. Other adverse events included tracheal ring fractures (17.1%), desaturations (6.8%), special incidents (6.2%), bleeding (5.5%), anesthesia complications (4.5%) and posterior tracheal wall injuries (1.1%). The use of TED in PDT is feasible, and the incidence of complications and adverse events was comparable with that of PDT using the flexible endoscope. Tracheal ring fractures in PDT cannot be avoided by the use of a rigid endoscope. With TED, the airway always remains open thus the use of jet ventilation via the TED during PDT is possible.