Abstract. HPV involvement in head and neck (HN) cancer is still under active investigation. Fresh frozen and archival clinical samples from 115 patients affected by HN carcinomas were analysed by PCR-based methods and direct sequencing. HPV types, intra-type variants, physical status, viral load and viral transcript presence were determined. HPV positivity was correlated with the main clinical-pathological features, including smoker and drinker status, and the clinical outcome. Twenty-one tumours were HPV positive (18.3%) with HPV16 being the most frequent type (n=14) followed by HPV6 (n=4), HPV33, HPV35, and HPV58 (n=1, each type). Tonsil carcinomas contained more high-risk HPV types (6/8; 75%) than all other sites (p=0.0004). HPV16 genome was integrated in all analysed tumours, as pure integrated form or mixed with concomitant episomal forms (4 cases). The viral load showed a wide variability (range, 0.7-485 copies per cell) with the highest value detected in a larynx tumour and the lowest one in a case of cancer of the oral cavity. In 9 HPVpositive samples where mRNA was available, transcripts of viral early oncogenes originating by integrated, episomal or mixed forms of the viral genome were found. A statistically significant correlation was evidenced between HPV and tumour differentiation, being the virus more associated with tumour grade G3/G4. Multivariate Cox regression analysis revealed that lymph-node and grade status were significant independent factors for a worse disease-free survival and overall survival, whereas the HPV status was associated with a better overall survival (OR, 0.33; 95% CI, 0.13-0.81; p=0.01). Taken together these results indicate that distinct pathological mechanisms for the malignant transformation in each single HN subsite should be taken in account; HPV molecular analyses should be considered a valid tool to distinguish subsets of oropharyngeal tumours and HPV presence could be useful for the prognostic assessment of HNSCC. IntroductionTumours of the oral cavity and pharynx have been estimated at 643,000 cases for 2002, with 349,000 deaths (1). The incidence of these cancers is traditionally found to be very high in some areas of the world (e.g., France and South India), but in the last decade other areas (e.g., Eastern Europe and Japan) reported an increasing incidence of head and neck (HN) squamous cell carcinomas (SCC) (2). HN cancer constitutes one of the most difficult pathologies to eradicate. Recurrences are frequent and about a half of patients die (1). The heterogeneity of treatment response and the lack of prognostic factors could be the main causes of the adverse clinical outcome. Moreover, the behaviour variability of each individual tumour has also emphasized the difficulties of managing these tumours.Life habits such as the intake of toxic agents present in tobacco smoke, alcohol drink and betel chewing, or poor hygiene remain major risk factors for these tumours. However, the fraction of HN cancers attributable to these risk factors is close to 80-90%, while the...

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The aim of the present study was to confirm the hypothesis that the cochlear efferent system is involved in the mechanisms underlying the "toughening" effect at high frequencies. The toughening effect is defined as a progressive threshold shift reduction when repeated exposures to the same noise are applied. Vestibular neurectomy was performed through a posterior cranial fossa approach in six healthy pigmented guinea pigs, and it assured the interruption of both crossed and uncrossed olivocochlear bundles to one ear only, before their entrance in the internal auditory meatus. The animals were then implanted with permanent electrodes for the electrocochleographic findings. Ten days after the operation the animals were exposed to octave-band toughening noise, centered at 4 kHz, at 85-dB SPL, for 10 consecutive days, 6 hours on/18 hours off. The hearing threshold was registered before and at the end of each exposure session. The behavior of the hearing threshold in the operated ears was then compared to that of the controlateral, nonoperated ears. Complete recovery from TS in the control ear began after four days of exposure, whereas in the operated ear hearing loss increased to day 7 (55 dB), with only a partial reduction (45 dB) beyond ten days of exposure. The results of the present study clearly demonstrated that sectioning of the OCB in guinea pigs causes persistent hearing loss during noise-exposure conditioning, in comparison to the contralateral, nonoperated ear. Thus, one can assume that the lack of decrease of TS during intermittent noise exposure could be due to the loss of the protective effect of the efferent fibers, perhaps mediated by the lateral OC neurons that synapse beneath the IHCs.

Using laser Doppler flowmetry, cochlear blood flow was assessed in Mongolian gerbils exposed to noise. Anesthetized animals were surgically implanted with permanent electrodes and then exposed for 10 consecutive days (6 h on/18 h off) to an octave band noise centered at 4 kHz (85 dB SPL). The auditory brainstem responses and the blood flow in the basal turn of the cochlea were compared with those of gerbils not exposed to noise. The exposed animals developed an initial threshold shift, followed by a progressive reduction in threshold shift up to complete recovery at the end of the test. In the exposed animals, a reduction in the cochlear blood flow during the first 4 days of exposure was observed, which was then followed by a progressive increase up to the end of the test. The results of this study exclude a possible role of the microvasculature of the lateral cochlear wall in determining the resistance to 4 kHz frequency noise exposure.

Using laser Doppler flowmetry, cochlear blood flow was assessed in Mongolian gerbils exposed to noise. Anesthetized animals were surgically implanted with permanent electrodes and then exposed for 10 consecutive days (6 h on/18 h off) to an octave band noise centered at 4 kHz (85 dB SPL). The auditory brainstem responses and the blood flow in the basal turn of the cochlea were compared with those of gerbils not exposed to noise. The exposed animals developed an initial threshold shift, followed by a progressive reduction in threshold shift up to complete recovery at the end of the test. In the exposed animals, a reduction in the cochlear blood flow during the first 4 days of exposure was observed, which was then followed by a progressive increase up to the end of the test. The results of this study exclude a possible role of the microvasculature of the lateral cochlear wall in determining the resistance to 4 kHz frequency noise exposure.