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Background A subset of HPV-associated oropharyngeal squamous cell carcinoma (HPV-OSCC) patients experience poor clinical outcomes. We explored prognostic risk factors on overall survival (OS) and recurrence free survival (RFS). Methods Patients with incident HPV-OSCC treated at the Johns Hopkins Hospital between 1997– 2008 with available tissue for HPV testing and demographic and clinicopathologic information (N=176) were included. Tissue was tested for HPV by in situ hybridization (ISH) and/or p16 immunohistochemistry (IHC). Demographic and clinicopathologic information was extracted from medical records. Results 90% (157/176) of the OSCC cases were HPV-associated. In the HPV-OSCC patients, we observed a 3- and 5-year OS rate of 93% (95% CI: 88%–98%) and 89% (95% CI: 81%–97%), respectively. Lower survival was observed with older patient age (HR 2.33 per 10-year increase, CI: 1.05–5.16, p=0.038), advanced clinical T-stage (HR 5.78, 95% CI: 1.60–20.8, p=0.007), and current tobacco use (HR 4.38, 95% CI: 1.07–18.0, p=0.04). Disease recurrence was associated with advanced clinical T stage (HR 8.32, 95% CI: 3.06–23, p<0.0001), current/former alcohol use (HR 13, 95% CI: 1.33–120, p=0.03), and unmarried status (HR 3.28, 95% CI: 1.20–9.00, p=0.02).. Patients who remained recurrence-free for 5 years had an 8.6% chance of recurrence by 10 years (one-sided 95% CI upper bound is 19%, p=0.088). Conclusions Prognostic risk factors are identified for HPV-OSCC patients. Observed recurrence rates between 5 and 10 years following definitive therapy needs to be validated in additional studies to determine whether extended cancer surveillance is warranted in this cancer population.

BackgroundNoise-induced hearing loss (NIHL) is the most prevalent form of acquired hearing loss and affects about 40 million US adults. Among the suggested therapeutics tested in rodents, suberoylanilide hydroxamic acid (SAHA) has been shown to be otoprotective from NIHL; however, these results were limited to male mice.MethodsHere we tested the effect of SAHA on the hearing of 10-week-old B6CBAF1/J mice of both sexes, which were exposed to 2 h of octave-band noise (101 dB SPL centered at 11.3 kHz). Hearing was assessed by measuring auditory brainstem responses (ABR) at 8, 16, 24, and 32 kHz, 1 week before, as well as at 24 h and 15–21 days following exposure (baseline, compound threshold shift (CTS) and permanent threshold shift (PTS), respectively), followed by histologic analyses.ResultsWe found significant differences in the CTS and PTS of the control (vehicle injected) mice to noise, where females had a significantly smaller CTS at 16 and 24 kHz (p < 0.0001) and PTS at 16, 24, and 32 kHz (16 and 24 kHz p < 0.001, 32 kHz p < 0.01). This sexual dimorphic effect could not be explained by a differential loss of sensory cells or synapses but was reflected in the amplitude and amplitude progression of wave I of the ABR, which correlates with outer hair cell (OHC) function. Finally, the frequency of the protective effect of SAHA differed significantly between males (PTS, 24 kHz, p = 0.002) and females (PTS, 16 kHz, p = 0.003), and the magnitude of the protection was smaller in females than in males. Importantly, the magnitude of the protection by SAHA was smaller than the effect of sex as a biological factor in the vehicle-injected mice.ConclusionsThese results indicate that female mice are significantly protected from NIHL in comparison to males and that therapeutics for NIHL may have a different effect in males and females. The data highlight the importance of analyzing NIHL experiments from males and females, separately. Finally, these data also raise the possibility of effectors in the estrogen signaling pathway as novel therapeutics for NIHL.Electronic supplementary materialThe online version of this article (10.1186/s13293-018-0171-0) contains supplementary material, which is available to authorized users.

BACKGROUND: Case-control studies from the early 2000s demonstrated that human papillomavirus-related oropharyngeal cancer (HPV-OPC) is a distinct entity associated with number of oral sex partners. Using contemporary data, we investigated novel risk factors (sexual debut behaviors, exposure intensity, and relationship dynamics) and serological markers on odds of HPV-OPC. METHODS: HPV-OPC patients and frequency-matched controls were enrolled in a multicenter study from 2013 to 2018. Participants completed a behavioral survey. Characteristics were compared using a chi-square test for categorical variables and a t test for continuous variables. Adjusted odds ratios (aOR) were calculated using logistic regression. RESULTS: A total of 163 HPV-OPC patients and 345 controls were included. Lifetime number of oral sex partners was associated with significantly increased odds of HPV-OPC (>10 partners: odds ratio [OR], 4.3 [95% CI, 2.8-6.7]). After adjustment for number of oral sex partners and smoking, younger age at first oral sex (<18 vs >20 years: aOR, 1.8 [95% CI, 1.1-3.2]) and oral sex intensity (>5 sex-years: aOR, 2.8 [95% CI, 1.1-7.5]) remained associated with significantly increased odds of HPV-OPC. Type of sexual partner such as older partners when a case was younger (OR, 1.7 [95% CI, 1.1-2.6]) or having a partner who had extramarital sex (OR, 1.6 [95% CI, 1.1-2.4]) was associated with HPV-OPC. Seropositivity for antibodies to HPV16 E6 (OR, 286 [95% CI, 122-670]) and any HPV16 E protein (E1, E2, E6, E7; OR, 163 [95% CI, 70-378]) was associated with increased odds of HPV-OPC. CONCLUSION: Number of oral sex partners remains a strong risk factor for HPV-OPC; however, timing and intensity of oral sex are novel independent risk factors. These behaviors suggest additional nuances of how and why some individuals develop HPV-OPC.

Objective: Inflammatory pseudotumor of the temporal bone is a benign, idiopathic inflammatory process that is locally invasive and a cause of significant morbidity. This study reviews our experience with seven patients and is currently the largest series to date. Study Design: Retrospective review from January 1, 2014 to January 1, 2016. Setting: Single tertiary medical center. Patients: There were five male and two female (n = 7) subjects with a diagnosis of temporal bone inflammatory pseudotumor. The mean age at presentation was 41 years old. The most common presenting symptoms were hearing loss (7/7) and headache (4/7). Four patients demonstrated an inflammatory aural polyp. Two patients experienced facial nerve paralysis. Intervention(s): Seven patients underwent computed tomography and six underwent magnetic resonance imaging. Corticosteroids and antibiotics were the initial treatment of choice. Five patients also underwent surgery. As adjuvant therapy, two patients received Rituximab, one patient received radiation, and one received mycophenolate mofetil. Main Outcome Measure(s): Clinical courses were followed with focus on symptoms, disease recurrence, duration, and treatment. Mean follow-up was 17.8 months. Results: The primary lesions demonstrated T2 hypo-intensity and enhancement as well as diffuse dural thickening on magnetic resonance imaging in five of six patients. Histopathology demonstrated chronic inflammation in the setting of hyalinized fibrosis (7/7). All the patients are currently symptomatically stable. Conclusion: Inflammatory pseudotumor of the temporal bone can cause devastating effects on neurological function and quality of life. Recognition of characteristic imaging and histopathology can expedite appropriate treatment. Patients may require chronic steroid therapy. Adjunctive therapy with radiation and immuno-modulation are currently being explored.