Cochlear implantation for rare Streptococcus suis meningitis with hearing loss.

OBJECTIVES: This study aimed to explore the diagnostic sensitivity of 3D heavily weighted T2-weighted MRI (T2MRI) and high-resolution computed tomography (HRCT) in patients with cochlear fibrosis associated with Streptococcus suis (S. suis) meningitis and the practicality of Cochlear implantation (CI) treatments. METHODS: Between January 2020 and December 2022, we enrolled four patients with rare cochlear S. suis meningitis with associated hearing loss despite aggressive or non-aggressive follow-up antibiotic treatment. Clinical imaging data, surgical performances and post-surgical-electrode impedance were evaluated. RESULTS: Combined with HRCT and T2MRI, the cochlea had varying degrees of fibrosis and ossification in different cases. However, the electrodes were successfully and wholly inserted after intraoperative removal of the ossified and fibrotic foci. Post-surgical electrode impedance values of MP1 + 2 mode were normal in all 4 cases at initial activation. CONCLUSION: In patients with S. suis meningitis and associated cochlear fibrosis, T2MRI examination of the inner ear was more sensitive than HRCT. This research highlights the feasibility of CI treatment in S. suis meningitis patients with severe cochlear fibrosis.

[Research progress in targeted delivery of inner ear using nanocarriers].

Various inner ear diseases such as sensorineural deafness and Meniere's disease bring about problems such as speech communication disorders and decreased work efficiency, which seriously affect the life quality of patients. Due to the special anatomical structure and blood-labyrinth barrier in the inner ear, the current drug administration methods are often unable to achieve satisfactory results. Nanocarriers are the forefront and hot spot of nanotechnology research. In recent years, a lot of research progress has been made in the field of targeted delivery of the inner ear, which is expected to be eventually applied to the treatment of clinical diseases of the inner ear. This review focuses on the advantages, main research achievements and limitations of various nanocarriers in the targeted delivery of the inner ear, hoping to provide new ideas for related research.

Desmoplastic small round cell tumor of bone revealed by 18F-FDG PET/CT: a case report with literature review.

A 50-year-old male presented with neck and shoulder pain. Chest CT and 18F-FDG PET/CT revealed osteolytic bone destruction in the left first rib and thoracic vertebrae with increased FDG uptake. Rib biopsy pathology indicated desmoplastic small round cell tumor (DSRCT).18F-FDG PET/CT can accurately locate the distribution of DSRCT and further guide the location of needle biopsy to assist the DSRCT.

A deep learning approach to the diagnosis of atelectasis and attic retraction pocket in otitis media with effusion using otoscopic images.

BACKGROUND: This study aimed to develop and validate a deep learning (DL) model to identify atelectasis and attic retraction pocket in cases of otitis media with effusion (OME) using multi-center otoscopic images. METHOD: A total of 6393 OME otoscopic images from three centers were used to develop and validate a DL model for detecting atelectasis and attic retraction pocket. A threefold random cross-validation procedure was adopted to divide the dataset into training validation sets on a patient level. A team of otologists was assigned to diagnose and characterize atelectasis and attic retraction pocket in otoscopic images. Receiver operating characteristic (ROC) curves, including area under the ROC curve (AUC), accuracy, sensitivity, and specificity were used to assess the performance of the DL model. Class Activation Mapping (CAM) illustrated the discriminative regions in the otoscopic images. RESULTS: Among all OME otoscopic images, 3564 (55.74%) were identified with attic retraction pocket, and 2460 (38.48%) with atelectasis. The diagnostic DL model of attic retraction pocket and atelectasis achieved a threefold cross-validation accuracy of 89% and 79%, AUC of 0.89 and 0.87, a sensitivity of 0.93 and 0.71, and a specificity of 0.62 and 0.84, respectively. Larger and deeper cases of atelectasis and attic retraction pocket showed greater weight, based on the red color depicted in the heat map of CAM. CONCLUSION: The DL algorithm could be employed to identify atelectasis and attic retraction pocket in otoscopic images of OME, and as a tool to assist in the accurate diagnosis of OME.

Delayed-onset swelling around the implant after cochlear implantation: a series of 26 patients.

PURPOSE: We aimed to clarify the clinical features of delayed-onset swelling around cochlear implants (CI), and to present our experience on how to avoid and address this problem. METHODS: We performed a retrospective review of all CI cases at our institution between June 2001 and June 2020. Information on postoperative complications of swelling in the receiver area > 3 months after implantation were analyzed, and clinical data sheets were drawn. RESULTS: Twenty-six of 1425 patients (1.82%) with an age at implantation ranging from 1 to 9 years experienced delayed-onset swelling around the implant. Swelling episodes occurred as early as 4 months, and as late as 178 months after implantation (median, 79.7 months). The predisposing factor in 12 cases was unclear, 7 cases were caused by trauma at the implantation site, 5 cases were without predisposing factors, and 2 cases were related to infection. We found the frequency of delayed-onset swelling after cochlear implantation with different incision was statistically insignificant (P = 0.423). Nineteen patients (73.1%) were cured after one treatment, and five patients (19.2%) relapsed. Follow-up examinations at least 18 months after surgery revealed that all patients experienced a complete recovery. CONCLUSIONS: Delayed-onset swelling at the receiver site is a long term but not exactly uncommon complication after cochlear surgery and long-term follow-up is eagerly required. It can recur more than once, causing more complex treatment strategies in clinical practice. Conservative treatment first recommended, while needle aspiration should initially be considered in recurrent cases also when the effusion swelling is > 3 ml.

Zwitterionic Polymer/Polydopamine Coating of Electrode Arrays Reduces Fibrosis and Residual Hearing Loss after Cochlear Implantation.

Since the first surgery 50 years ago, cochlear implantation (CI) is the major treatment for patients with severe sensorineural hearing loss. However, unexpected foreign body reactions (FBRs) after surgery are reported in 90% of CI recipients, resulting in the formation of fibrosis in the cochlea and progressive residual hearing loss. Zwitterion modification is universally used to reduce bio-fouling and suppress FBRs but never for CI. In the present study, a zwitterionic coating is developed, which is composed of poly sulfobetaine methacrylate (PSB) and polydopamine (PDA) for cochlear implants. The PSB-PDA coating shows a series of characters for an ideal anti-FBRs material, including super-hydrophilicity, low protein and cell adsorption, long-term stability, and high biocompatibility. Compared to the uncoated controls, PSB-PDA coating inhibits the activation of macrophages and reduces the release of inflammatory factors (TNF-α, IL-1ß, NO) and fibrosis-related factors (TGF-ß1, α-SMA, collagen I). PSB-PDA coated electrode arrays suppress fibrosis completely and preserve residual hearing significantly in rat CI models. These results suggest that PSB-PDA coating is a novel strategy for anti-fibrosis to improve the outcomes of CI.

Long-Term Release of Dexamethasone With a Polycaprolactone-Coated Electrode Alleviates Fibrosis in Cochlear Implantation.

Cochlear implantation (CI) is the major treatment for severe sensorineural hearing loss. However, the fibrotic tissue forming around the electrodes reduces the treatment effectiveness of CI. Dexamethasone (DEX) is usually applied routinely in perioperative treatment of cochlear implantation (CI), but its diffusion in the inner ear after systemic administration is limited. In the present study, an electrode coated with polycaprolactone (PCL) loaded with dexamethasone was developed with a simple preparation process to maintain the stability of the electrode itself. The DEX-loaded PCL coating has good biocompatibility and does not change the smoothness, flexibility, or compliance of the implant electrode. Stable and effective DEX concentrations were maintained for more than 9 months. Compared with the pristine electrode, decreasing intracochlear fibrosis, protection of hair cells and spiral ganglion cells, and better residual hearing were observed 5 weeks after PCL-DEX electrode implantation. The PCL-DEX electrode has great potential in preventing hearing loss and fibrosis by regulating macrophages and inhibiting the expression of the fibrosis-related factors IL-1ß, TNF-α, IL-4, and TGF-ß1. In conclusion, the PCL-DEX electrode coating shows promising application in CI surgery.

Low-Intensity Ultrasound Causes Direct Excitation of Auditory Cortical Neurons.

Cochlear implantation is the first-line treatment for severe and profound hearing loss in children and adults. However, deaf patients with cochlear malformations or with cochlear nerve deficiencies are ineligible for cochlear implants. Meanwhile, the limited spatial selectivity and high risk of invasive craniotomy restrict the wide application of auditory brainstem implants. A noninvasive alternative strategy for safe and effective neuronal stimulation is urgently needed to address this issue. Because of its advantage in neural modulation over electrical stimulation, low-intensity ultrasound (US) is considered a safe modality for eliciting neural activity in the central auditory system. Although the neural modulation ability of low-intensity US has been demonstrated in the human primary somatosensory cortex and primary visual cortex, whether low-intensity US can directly activate auditory cortical neurons is still a topic of debate. To clarify the direct effects on auditory neurons, in the present study, we employed low-intensity US to stimulate auditory cortical neurons in vitro. Our data show that both low-frequency (0.8 MHz) and high-frequency (>27 MHz) US stimulation can elicit the inward current and action potentials in cultured neurons. c-Fos staining results indicate that low-intensity US is efficient for stimulating most neurons. Our study suggests that low-intensity US can excite auditory cortical neurons directly, implying that US-induced neural modulation can be a potential approach for activating the auditory cortex of deaf patients.

Preparation, characterization and application research of a sustained dexamethasone releasing electrode coating for cochlear implantation.

Cochlear inflammatory response after cochlear implantation (CI) is an important mechanism for implantation trauma and hearing loss. The hearing loss was also caused by damage to auditory hair cells (HCs), whereas ion homeostasis within the cochlea can ensure survival of HCs. In our study, pure hyaluronic acid (HA) was crosslinked with 1, 4-butanediol diglycidyl ether (BDDE) and the successful preparation of the cross-linked hydrogel (CHA) was confirmed by rheological characteristics and FTIR spectra. Artificial perilymph (APL) was prepared to simulate the ion homeostasis microenvironment within scala tympani of human cochlear, and served as the major component of artificial perilymph soaked CHA (APL-CHA). The conductivity experiment indicated that APL-CHA is more suitable to the requirements of the electrical conductivity in scala tympani. The electrode coating process found that the extrusion coating method have advantages of controllable adhesive capacity of APL-CHA, uniform coating thickness and smooth surface as compared to common method. Due to CI surgery application requirement, optimization of coating process was selected as follows: extrusion coating method, degree of 3.6 vol%, pinhole diameter of 32G (110 µm), pressure of 200 ±â€¯15.81 Psi. Controlled dexamethasone 21-phosphate sodium salt (DSP) release of 20 days could be demonstrated using the hydrogel filled reservoir via a validated HPLC method. The morphological structure of CHA showed different sizes of porous structure among APL-CHA provided structural basis for drug delivery. L929 fibroblasts culture and Spiral Ganglion Neuron Explants culture results revealed that APL-CHA possesses fine biological compatibility. APL-CHA shows a promising application in CI surgery and has great potential in preventing hearing loss with well simulation of ion homeostasis within the cochlear, local DSP delivery for target anti-inflammatory, approximate conductivity within the scala tympani and optimization of electrode coating process.

Label-free hyperspectral imaging and quantification methods for surgical margin assessment of tissue specimens of cancer patients.

Hyperspectral imaging (HSI) is a relatively new modality in medicine and can have many potential applications. In this study, we developed label-free hyperspectral imaging for tumor margin assessment. HSI data, hypercube (x,y,λ), consists of a series of images of the same field of view that are acquired at different wavelengths. Every pixel in the hypercube has an optical spectrum. We collected surgical tissue specimens from 16 human subjects who underwent head and neck (H&N) cancer surgery. We acquired both HSI, autofluorescence images, and fluorescence images with 2-NBDG and proflavine from the specimens. Digitized histologic slides were examined by an H&N pathologist. We developed image preprocessing and classification methods for HSI data and differentiate cancer from benign tissue. The hyperspectral imaging and classification method was able to distinguish between cancer and normal tissue from oral cavity with an average accuracy of 90±8%, sensitivity of 89±9%, and specificity of 91±6%. This study suggests that label-free hyperspectral imaging has great potential for surgical margin assessment in tissue specimens of H&N cancer patients. Further development of the imaging technology and quantification methods is warranted for its application in image-guided surgery.

Prognostic biomarkers in patients with human immunodeficiency virus-positive disease with head and neck squamous cell carcinoma.

BACKGROUND: We examined the prognostic value of a panel of biomarkers in patients with squamous cell carcinoma of the head and neck (SCCHN) who were human immunodeficiency virus (HIV) positive (HIV-positive head and neck cancer) and HIV negative (HIV-negative head and neck cancer). METHODS: Tissue microarrays (TMAs) were constructed using tumors from 41 disease site-matched and age-matched HIV-positive head and neck cancer cases and 44 HIV-negative head and neck cancer controls. Expression of tumor biomarkers was assessed by immunohistochemistry (IHC) and correlations examined with clinical variables. RESULTS: Expression levels of the studied oncogenic and inflammatory tumor biomarkers were not differentially regulated by HIV status. Among patients with HIV-positive head and neck cancer, laryngeal disease site (P = .003) and Clavien-Dindo classification IV (CD4) counts <200 cells/µL (P = .01) were associated with poor prognosis. Multivariate analysis showed that p16 positivity was associated with improved overall survival (OS; P < .001) whereas increased expression of transforming growth factor-beta (TGF-ß) was associated with poor clinical outcome (P = .001). CONCLUSION: Disease site has significant effect on the expression of biomarkers. Expression of tumor TGF-ß could be a valuable addition to the conventional risk stratification equation for improving head and neck cancer disease management strategies.

Label-free reflectance hyperspectral imaging for tumor margin assessment: a pilot study on surgical specimens of cancer patients.

A label-free, hyperspectral imaging (HSI) approach has been proposed for tumor margin assessment. HSI data, i.e., hypercube (x,y,λ), consist of a series of high-resolution images of the same field of view that are acquired at different wavelengths. Every pixel on an HSI image has an optical spectrum. In this pilot clinical study, a pipeline of a machine-learning-based quantification method for HSI data was implemented and evaluated in patient specimens. Spectral features from HSI data were used for the classification of cancer and normal tissue. Surgical tissue specimens were collected from 16 human patients who underwent head and neck (H&N) cancer surgery. HSI, autofluorescence images, and fluorescence images with 2-deoxy-2-[(7-nitro-2,1,3-benzoxadiazol-4-yl)amino]-D-glucose (2-NBDG) and proflavine were acquired from each specimen. Digitized histologic slides were examined by an H&N pathologist. The HSI and classification method were able to distinguish between cancer and normal tissue from the oral cavity with an average accuracy of 90%±8%, sensitivity of 89%±9%, and specificity of 91%±6%. For tissue specimens from the thyroid, the method achieved an average accuracy of 94%±6%, sensitivity of 94%±6%, and specificity of 95%±6%. HSI outperformed autofluorescence imaging or fluorescence imaging with vital dye (2-NBDG or proflavine). This study demonstrated the feasibility of label-free, HSI for tumor margin assessment in surgical tissue specimens of H&N cancer patients. Further development of the HSI technology is warranted for its application in image-guided surgery.

Detection of Head and Neck Cancer in Surgical Specimens Using Quantitative Hyperspectral Imaging.

Purpose: This study intends to investigate the feasibility of using hyperspectral imaging (HSI) to detect and delineate cancers in fresh, surgical specimens of patients with head and neck cancers.Experimental Design: A clinical study was conducted in order to collect and image fresh, surgical specimens from patients (N = 36) with head and neck cancers undergoing surgical resection. A set of machine-learning tools were developed to quantify hyperspectral images of the resected tissue in order to detect and delineate cancerous regions which were validated by histopathologic diagnosis. More than two million reflectance spectral signatures were obtained by HSI and analyzed using machine-learning methods. The detection results of HSI were compared with autofluorescence imaging and fluorescence imaging of two vital-dyes of the same specimens.Results: Quantitative HSI differentiated cancerous tissue from normal tissue in ex vivo surgical specimens with a sensitivity and specificity of 91% and 91%, respectively, and which was more accurate than autofluorescence imaging (P < 0.05) or fluorescence imaging of 2-NBDG (P < 0.05) and proflavine (P < 0.05). The proposed quantification tools also generated cancer probability maps with the tumor border demarcated and which could provide real-time guidance for surgeons regarding optimal tumor resection.Conclusions: This study highlights the feasibility of using quantitative HSI as a diagnostic tool to delineate the cancer boundaries in surgical specimens, and which could be translated into the clinic application with the hope of improving clinical outcomes in the future. Clin Cancer Res; 23(18); 5426-36. ©2017 AACR.

Tumor margin assessment of surgical tissue specimen of cancer patients using label-free hyperspectral imaging.

We are developing label-free hyperspectral imaging (HSI) for tumor margin assessment. HSI data, hypercube (x,y,λ), consists of a series of high-resolution images of the same field of view that are acquired at different wavelengths. Every pixel on the HSI image has an optical spectrum. We developed preprocessing and classification methods for HSI data. We used spectral features from HSI data for the classification of cancer and benign tissue. We collected surgical tissue specimens from 16 human patients who underwent head and neck (H&N) cancer surgery. We acquired both HSI, autofluorescence images, and fluorescence images with 2-NBDG and proflavine from the specimens. Digitized histologic slides were examined by an H&N pathologist. The hyperspectral imaging and classification method was able to distinguish between cancer and normal tissue from oral cavity with an average accuracy of 90±8%, sensitivity of 89±9%, and specificity of 91±6%. For tissue specimens from the thyroid, the method achieved an average accuracy of 94±6%, sensitivity of 94±6%, and specificity of 95±6%. Hyperspectral imaging outperformed autofluorescence imaging or fluorescence imaging with vital dye (2-NBDG or proflavine). This study suggests that label-free hyperspectral imaging has great potential for tumor margin assessment in surgical tissue specimens of H&N cancer patients. Further development of the hyperspectral imaging technology is warranted for its application in image-guided surgery.

HER3 Targeting Sensitizes HNSCC to Cetuximab by Reducing HER3 Activity and HER2/HER3 Dimerization: Evidence from Cell Line and Patient-Derived Xenograft Models.

PURPOSE: Our previous work suggested that HER3 inhibition sensitizes head and neck squamous cell carcinoma (HNSCC) to EGFR inhibition with cetuximab. This study aimed to define the role of HER3 in cetuximab resistance and the antitumor mechanisms of EGFR/HER3 dual targeting in HNSCC. EXPERIMENTAL DESIGN: We treated cetuximab-resistant HNSCC UMSCC1-C and parental UMSCC1-P cell lines with anti-EGFR antibody cetuximab, anti-HER3 antibody MM-121, and their combination. We assessed activities of HER2, HER3, and downstream signaling pathways by Western blotting and cell growth by sulforhodamine B (SRB) and colony formation assays. HER3-specific shRNA was used to confirm the role of HER3 in cetuximab response. The combined efficacy and alterations in biomarkers were evaluated in UMSCC1-C xenograft and patient-derived xenograft (PDX) models. RESULTS: Cetuximab treatment induced HER3 activation and HER2/HER3 dimerization in HNSCC cell lines. Combined treatment with cetuximab and MM-121 blocked EGFR and HER3 activities and inhibited the PI3K/AKT and ERK signaling pathways and HNSCC cell growth more effectively than each antibody alone. HER3 knockdown reduced HER2 activation and resensitized cells to cetuximab. Cetuximab-resistant xenografts and PDX models revealed greater efficacy of dual EGFR and HER3 inhibition compared with single antibodies. In PDX tissue samples, cetuximab induced HER3 expression and MM-121 reduced AKT activity. CONCLUSIONS: Clinically relevant PDX models demonstrate that dual targeting of EGFR and HER3 is superior to EGFR targeting alone in HNSCC. Our study illustrates the upregulation of HER3 by cetuximab as one mechanism underlying resistance to EGFR inhibition in HNSCC, supporting further clinical investigations using multiple targeting strategies in patients who have failed cetuximab-based therapy. Clin Cancer Res; 23(3); 677-86. ©2016 AACR.

Hyperspectral Imaging of Neoplastic Progression in a Mouse Model of Oral Carcinogenesis.

Hyperspectral imaging (HSI) is an emerging modality for medical applications and holds great potential for noninvasive early detection of cancer. It has been reported that early cancer detection can improve the survival and quality of life of head and neck cancer patients. In this paper, we explored the possibility of differentiating between premalignant lesions and healthy tongue tissue using hyperspectral imaging in a chemical induced oral cancer animal model. We proposed a novel classification algorithm for cancer detection using hyperspectral images. The method detected the dysplastic tissue with an average area under the curve (AUC) of 0.89. The hyperspectral imaging and classification technique may provide a new tool for oral cancer detection.

Quantitative Diagnosis of Tongue Cancer from Histological Images in an Animal Model.

We developed a chemically-induced oral cancer animal model and a computer aided method for tongue cancer diagnosis. The animal model allows us to monitor the progress of the lesions over time. Tongue tissue dissected from mice was sent for histological processing. Representative areas of hematoxylin and eosin (H&E) stained tissue from tongue sections were captured for classifying tumor and non-tumor tissue. The image set used in this paper consisted of 214 color images (114 tumor and 100 normal tissue samples). A total of 738 color, texture, morphometry and topology features were extracted from the histological images. The combination of image features from epithelium tissue and its constituent nuclei and cytoplasm has been demonstrated to improve the classification results. With ten iteration nested cross validation, the method achieved an average sensitivity of 96.5% and a specificity of 99% for tongue cancer detection. The next step of this research is to apply this approach to human tissue for computer aided diagnosis of tongue cancer.

Biomarker quantification by multiplexed quantum dot technology for predicting lymph node metastasis and prognosis in head and neck cancer.

PURPOSE: To predict lymph node metastasis and prognosis in head and neck squamous cell carcinoma (HNSCC). RESULTS: The combination of membranous E-cadherin and membranous epidermal growth factor receptor (EGFR) quantified by QD technology with age, gender, and grade had greater predictive power than any of the single biomarkers or the two combined biomarkers quantified by conventional immunohistochemistry (IHC). The predictive power of this model was validated in another independent sample set; the predictive sensitivity of this model for LNM was 87.5%, with specificity up to 97.4%, and accuracy 92.9%. Furthermore, a higher membranous E-cadherin level was significantly correlated with better overall and disease-free survival (OS, DFS; P = 0.002, 0.033, respectively), while lower cytoplasmic vimentin and membranous EGFR levels were significantly correlated with better OS (P = 0.016 and 0.021, respectively). The combined biomarkers showed a stronger prognostic value for OS and DFS than any of the single biomarkers. METHODS: Multiplexed quantum dots (QDs) were used to simultaneously label E-cadherin, vimentin, and EGFR with ß-actin as an internal control. Primary tissue samples from 97 HNSCC patients, 49 with and 48 without LNM were included in the training set. Levels of membranous E-cadherin, cytoplasmic vimentin, and membranous EGFR were quantified by InForm software and correlated with clinical characteristics. CONCLUSIONS: Multiplexed subcellular QD quantification of EGFR and E-cadherin is a potential strategy for the prediction of LNM, DFS, and OS of HNSCC patients.

Preparation and performance of a pH-sensitive cisplatin-loaded magnetic nanomedicine that targets tumor cells via folate receptor mediation.

The present study aimed to prepare cisplatin (CDDP)-loaded magnetic nanoparticles (MNPs), which target folate receptors via a pH-sensitive release system (FA­PEG­NH­N=MNPs­CDDP). This is of interest for the development of intelligent drug delivery systems that target tumors of the head and neck. The chemical coprecipitation method was used to prepare ferroferric oxide MNPs. These were modified with aldehyde sodium alginate complexed with the chemotherapeutic agent, CDDP on the surface of the nanoparticles. Double hydrazine­poly(ethylene glycol; PEG) was also prepared by attaching the carboxyl group of hydrazine­folate on one side of the double hydrazine­PEG, obtaining folate­hydrazine­PEG­diazenyl. This binds the aldehyde group of sodium alginic acid on the MNP to enclose CDDP, in order that it is sequestered within the carrier. This method obtained a pH­sensitive, FA­modified CDDP­loaded MNP (FA­PEG­NH­N=MNPs­CDDP), which acts as an intelligent tumor targeting drug delivery system. The mean size of the MNPs was ~10.2±1.5 nm, the mean hydrodynamic diameter detected by laser particle sizing instruments was 176.6±1.1 nm, and the ζ­potential was ­20.91±1.76 mV. The CDDP content was 0.773 mg/ml, the iron content was ~1.908 mg/ml and the maximum saturation magnetization was 16.3±0.2 emu/g. The current study produced a pH­sensitive FA­modified CDDP­loaded MNP that is stable and exhibits magnetic responsiveness, which releases CDDP in a low pH environment.

A novel prediction model for human papillomavirus-associated oropharyngeal squamous cell carcinoma using p16 and subcellular ß-catenin expression.

BACKGROUND: p16 overexpression is a highly sensitive yet moderately specific biomarker for predicting human papillomavirus (HPV)-associated oropharyngeal squamous cell carcinoma (OPSCC). Nuclear ß-catenin translocation has been linked to HPV-positive OPSCC. However, whether the strategy of combining ß-catenin with p16 can better predict HPV-associated OPSCC remains unknown. METHODS: We evaluated the expression of p16 and ß-catenin (nuclear and membrane) by immunohistochemistry staining in 101 OPSCC tissues and HPV status by HPV DNA in situ hybridization. Logistic regression models were used to evaluate single or multiple biomarkers for HPV prediction. The prediction power, sensitivity, and specificity were determined by receiver operating characteristic (ROC) analyses. RESULTS: Our data showed that upon univariate analysis, p16 and nuclear ß-catenin were positively correlated with HPV status, while membrane ß-catenin was inversely correlated with HPV status (P < 0.01). p16 showed the highest HPV predictive power, with area under the curve (AUC) of 0.9074 compared to 0.6762 for nuclear ß-catenin and 0.7635 for membrane ß-catenin, respectively, indicating differential accuracies for HPV prediction. Multivariable analysis showed that p16 was significantly correlated with HPV, while nuclear and membrane ß-catenin showed marginal significance. The three-biomarker model was similarly sensitive (98.9% vs. 100%) but more specific (88.9% vs. 81%) than p16 alone, which also showed a good predictive value for overall (P = 0.0002) survival and disease-free (P = 0.0158) survival. CONCLUSION: Our study suggests a novel model of combining p16 and subcellular ß-catenin for prediction of HPV-associatred OPSCC, and this finding deserves further validation.