Oral Human Papillomavirus in Women With High-Grade Cervical Intraepithelial Neoplasia.

OBJECTIVE: This study was designed to investigate the co-prevalence of cervical and oropharyngeal human papillomavirus (HPV) infection in patients with HPV-related high-grade disease of the uterine cervix (high-grade squamous intraepithelial lesion [HSIL]). MATERIALS AND METHODS: In a prospective cohort study, women with abnormal cervical cytology admitted to our colposcopy units received HPV testing of the uterine cervix and the oropharynx via smear. From a subset of patients, oral lavage was collected to compare detection rates of HPV DNA between lavage and swab. Patients with confirmed high-risk HPV (HR-HPV)-positive HSIL of the cervix were further investigated. Sexual behavior and lifestyle factors were documented with a standardized questionnaire. RESULTS: Two hundred thirty-five women were included in the study. Of the 235 women, 135 (57.5%) were cervically HR-HPV positive with histologically confirmed high-grade cervical intraepithelial lesion (median [range] age = 30 [21-45] years). Of these, only 6 (4.4%) also had a positive oral specimen. In 3 (50%) of the 6 cases, the same HPV type was detected in oral and cervical samples (HPV 16, 35, and 45). Oral HPV detection was not higher when combining swab and lavage compared with swab alone. A relation between sexual behavior and oral HPV detection could not be demonstrated. CONCLUSIONS: Oral HPV prevalence in women with cervical HPV infection and HSIL is low. Simultaneous testing of oropharyngeal and cervical HPV infection does not seem promising as future screening strategy.

Epidemiology of laryngeal carcinoma in Germany, 1998-2011.

Constituting 25-30 % of all head and neck cancer cases, laryngeal carcinoma is the most prevalent entity. Major risk factors of laryngeal cancer are smoking and excessive alcohol consumption. This study presents the recent developments in the incidence of laryngeal cancer from 1998 to 2011 in Germany. Laryngeal carcinoma was identified using International Statistical Classification of Diseases and Related Health Problems (ICD10) from German population-based cancer registries. The incidence was provided by the Robert Koch Institute, and the mortality data were derived from German death statistics for further evaluation. Both descriptive and analytical analyses were conducted. From 1998 to 2011, a total of 14,847 laryngeal carcinoma cases were reported, in 13,195 men and 1652 women. Glottic carcinoma represented the main entity, constituting 69 % of male cases and 50 % of female cases. For men, a decline in incidence was observed starting in 2006. The incidence rate for women remained stable for the period of observation. The incidence of laryngeal cancer resembles the development of smoking behaviour in Germany. To maintain the positive trend of the male population and to reduce the incidence in women, it is crucial to continue and to improve the prevention of smoking campaigns in Germany.

Oral HPV prevalence in women positive for cervical HPV infection and their sexual partners: a German screening study.

The incidence of human papillomavirus (HPV) associated oropharyngeal squamous cell cancer (OSCC) is on the rise. With the HPV-positive uterine cervix as a reservoir, HPV-positive OSCC is discussed as a sexually transmitted disease. Mechanisms of HPV transmission to the oral cavity are poorly understood. To gain more insight into HPV-transmission routes, cervically HPV-positive women and their sexual partners are screened for oral HPV infection. Women with cervical dysplasia underwent HPV testing of the uterine cervix and tonsillar region via brush test. In addition, sexual partners received oral HPV testing. Tonsillar brush tests of patients admitted for routine surgery served as the control group. The HPV-PCR (Roche Linear Array Kit) was used to differentiate 37 HPV types. All participants completed a risk-factor questionnaire focusing on sexual habits. 101 women were tested HPV-positive at the cervix. Only 3/101 (3 %) were tested HPV-positive in the oropharynx. In 60/101 (60 %) women the sexual partner could be tested for oral HPV infection: testing was positive in 3/60 (5 %). No oral HPV was detected in the control group. The risk-factor questionnaire revealed significant differences between the female study- and control group in terms of age at first sexual intercourse and smoking habits. The limited data suggest that among sexual partners in Germany, HPV transmission to the oropharynx by oral-genital sex or by autoinoculation is a rare and unlikely event with low HPV concordance. Another explanation for the low oral prevalence could be an independent clearance of HPV from the oropharyngeal site compared to cervix uteri or at different time intervals.

Intensity modulated perioperative HDR brachytherapy for recurrent and/or advanced head and neck metastases.

Recurrent neck metastases following surgery and full dose adjuvant radiotherapy of squamous cell head and neck cancer remain a clinical challenge. After revision neck dissection and chemotherapy re-irradiation dosage is often limited and survival prognosis deteriorates. Here, adjuvant high-dose rate intensity modulated perioperative brachytherapy (HDR IMBT) offers a second full radiation dose with a limited volume of normal tissue radiation in the neck. In this retrospective study patients were identified who underwent revision surgery and perioperative HDR IMBT for recurrent neck metastases. Survival rates were estimated and the scarce literature on interstitial brachytherapy of the neck was reviewed. From 2006 to 2014, nine patients were treated for recurrent or palliative neck metastases using salvage surgery and HDR IMBT. Eight patients received previous surgery and external beam radiotherapy with or without chemotherapy. Two and five year overall survival was calculated to be 78 and 67 %, respectively. HDR IMBT is a salvage treatment option for selected cases in the neck following surgical revision or last-line treatment strategies. In the literature and this small cohort radiation toxicity and the risk of "carotid blow-out" seemed to be low.

Comparison of PapilloCheck and Linear Array to Detect and Differentiate Human Papillomaviruses in Cervical and Tonsillar Smears from Females with Cervical Intraepithelial Lesions.

A subgroup of oropharyngeal squamous cell carcinomas (OSCCs) are causally linked to infection with high-risk human papillomaviruses (HR-HPVs). To evaluate the prevalence of simultaneous oral HPV infection in females with cervical high-grade squamous intraepithelial lesions (HSIL), tonsillar- and cervical smears were collected simultaneously from 73 patients and analyzed for HPV using two commercial assays, PapilloCheck (Greiner-Bio-One) and Linear Array (Roche). Only 3/73 (4.1%) tonsillar smears were HPV positive (HPV+), with HPV types 16, 35, and 45, respectively, detected by both assays (100% agreement). Concordant results were also found in 60/66 (91%) evaluable cervical smears. Of specimens, positive by both assays, typing results completely coincide in 71% (all types are identical) and partially coincide in 27% (at least one type is identical). Taken together, results of HPV detection and typing by PapilloCheck and Linear Array are highly congruent and confirm the low prevalence of HR-HPV in tonsillar smears of patients with HSIL of the uterine cervix. Our data indicate low prevalence of oropharyngeal HPV infection in patients with high-grade cervical dysplasia. The low detection rate was confirmed by using two different commercial assays with largely consistent results of HPV detection and typing, but with some variation for particular HPV types. Comparative testing of larger numbers is required to identify the HPV types prone to escape detection with particular assays.

The hemicochlea preparation of the guinea pig and other mammalian cochleae.

The hemicochlea and its slice preparation is a novel method that allows access to various cochlear structures without the physical distortion that typically occurs from tissue dehydration during the embedding process. Therefore, the hemicochlea preparation provides an excellent model to study (1) cochlear morphology during cochlear development, (2) malformation caused by genetic defects, (3) changes related to diseases, (4) sensory physiology, (5) cochlear micromechanics, and (6) the expression of proteins by immunohistochemistry. This paper describes in detail the method of slicing hemicochleae for different mammalian species, including mice, rats, gerbils, guinea pigs, pigs, and human temporal bones. Furthermore, guinea pig cochleae are used as an example to provide cochlear dimensions of important anatomical structures. The values obtained in eight guinea pig hemicochleae are compared to published values, and upon review, discrepancies do exist. For example, gelatinous structures, such as the tectorial membrane, appear larger in the hemicochlea when compared to traditional embedding. Dimensions obtained for selected cochlear structures at different locations along the guinea pig cochleae provide an improved basis for cochlear models.

Optical stimulation of the facial nerve: a new monitoring technique?

OBJECTIVES/ HYPOTHESIS: One sequela of skull base surgery is iatrogenic damage to cranial nerves, which can be prevented if the nerve is identified. Devices that stimulate nerves with electric current assist in nerve identification. Contemporary devices have two main limitations: 1) the physical contact of the stimulating electrode and (2) the spread of the current through the tissue. In contrast to electrical stimulation, pulsed infrared optical radiation can be used to safely and selectively stimulate neural tissue and might be valuable for screening. METHODS: The gerbil facial nerve was exposed to 250 microsecond pulses of 2.12 microm radiation delivered via a 600-microm-diameter optical fiber at a repetition rate of 2 Hz. With use of 27 GA, 12-mm intradermal electrodes, muscle action potentials were recorded. Nerve samples were examined for possible tissue damage. RESULTS: Eight facial nerves were stimulated with radiant exposures between 0.71 and 1.77 J/cm, resulting in compound muscle action potentials (CmAPs) that were simultaneously measured at the m. orbicularis oculi, m. levator nasolabialis, and m. orbicularis oris. Resulting CmAP amplitudes were 0.3 to 0.4 mV, 0.15 to 1.4 mV, and 0.3 to 2.3 mV, respectively, depending on the radial location of the optical fiber and the radiant exposure. Individual nerve branches were also stimulated, resulting in CmAP amplitudes between 0.2 and 1.6 mV. Histology revealed tissue damage at radiant exposures of 2.2 J/cm but no apparent damage at radiant exposures of 2.0 J/cm. CONCLUSIONS: The experiments showed that selective muscle action potentials can be evoked optically in the gerbil facial nerve without direct physical contact.

Perioperative image-adapted brachytherapy for the treatment of paranasal sinus and nasal cavity malignancies.

PURPOSE: Sinonasal malignancies are a rare group of cancers often associated with late presentation and poor prognosis. In the past, there was little progress regarding survival rate, and often, multimodal treatment regimens are required. The aim of this study was to evaluate the clinical outcome of perioperative image-adapted brachytherapy (IABT) as part of a multidisciplinary treatment regimen for the therapy of sinonasal cancer. METHODS AND MATERIALS: Since 2006, patients with sinonasal cancer at the University Hospital of Schleswig-Holstein Campus Luebeck, Germany, were offered a multimodal treatment concept including head and neck surgery, perioperative IABT with or without external beam radiation therapy, and chemotherapy. In a retrospective study, such patients were analyzed for survival rate, tumor control, and toxicity of the interdisciplinary treatment. RESULTS: Thirty-five consecutive patients were analyzed. The majority of patients (63%) were treated for a primary tumor and 62% presented with tumor Stages III-IV. The mean follow-up time with IABT was 28 months. Overall survival estimate was 72% after 3 years. Disease-specific survival, disease-free survival, and local control rates were 83%, 63%, and 67%, respectively. On univariate analysis, a significant better disease-free survival rate was found in patients treated for primary, but not recurrent, sinonasal cancer (p = 0.006). The overall treatment toxicities were mainly classified Grade I. CONCLUSIONS: Interdisciplinary perioperative IABT is associated with excellent locoregional control and survival rates. IABT is well tolerated and shows low toxicity. Furthermore, visual acuity can be preserved in advanced cases. The implementation of perioperative IABT into multimodal treatment regimens improves the oncologic outcome.

Nanosecond laser pulse stimulation of the inner ear-a wavelength study.

Optical stimulation of the inner ear, the cochlea, is discussed as a possible alternative to conventional cochlear implants with the hypothetical improvement of dynamic range and frequency resolution. In this study nanosecond-pulsed optical stimulation of the hearing and non-hearing inner ear is investigated in vivo over a wide range of optical wavelengths and at different beam delivery locations. Seven anaesthetized guinea pigs were optically stimulated before and after neomycin induced destruction of hair cells. An optical parametric oscillator was tuned to different wavelengths (420 nm-2150 nm, ultraviolet to near-infrared) and delivered 3-5 ns long pulses with 6 µJ pulse energy via a multimode optical fiber located either extracochlearly in front of the intact round window membrane or intracochlearly within the scala tympani. Cochlear responses were measured using registration of compound action potentials (CAPs). With intact hair cells CAP similar to acoustic stimulation were measured at both locations, while the neomycin treated cochleae did not show any response in any case. The CAP amplitudes of the functional cochleae showed a positive correlation to the absorption coefficient of hemoglobin and also to moderate water absorption. A negative correlation of CAP amplitude with a water absorption coefficient greater than 5.5 cm(-1) indicates additional phenomena. We conclude that in our stimulation paradigm with ns-pulses the most dominant stimulation effect is of optoacoustic nature and relates to functional hair cells.

Acoustic events and "optophonic" cochlear responses induced by pulsed near-infrared laser.

Optical stimulation of neural tissue within the cochlea was described as a possible alternative to electrical stimulation. Most optical stimulation was performed with pulsed lasers operating with near-infrared (NIR) light and in thermal confinement. Under these conditions, the coexistence of laser-induced optoacoustic stimulation of the cochlea ("optophony") has not been analyzed yet. This study demonstrates that pulsed 1850-nm laser light used for neural stimulation also results in sound pressure levels up to 62 dB peak-to-peak equivalent sound pressure level (SPL) in air. The sound field was confined to a small volume along the laser beam. In dry nitrogen, laser-induced acoustic events disappeared. Hydrophone measurements demonstrated pressure waves for laser fibers immersed in water. In hearing rats, laser-evoked signals were recorded from the cochlea without targeting neural tissue. The signals showed a two-domain response differing in amplitude and latency functions, as well as sensitivity to white-noise masking. The first component had characteristics of a cochlear microphonic potential, and the second component was characteristic for a compound action potential. The present data demonstrate that laser-evoked acoustic events can stimulate a hearing cochlea. Whenever optical stimulation is used, care must be taken to distinguish between such "optophony" and the true optoneural response.