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Fakhry C.,Milton nce Jr Head And Neck Center | Andersen K.K.,Danish Cancer Society | Christensen J.,Danish Cancer Society
Cancer Prevention Research | Year: 2015

The incidence of oropharyngeal carcinoma, involving palatine and lingual tonsils, is increasing globally. This significant rise is driven by human papillomavirus. Whether palatine tonsillectomy affects risk of diagnosis with oropharyngeal carcinoma is unknown. The association between tonsillectomy and incidence of oropharyngeal carcinoma was explored in the Danish Cancer Registry. The association between tonsillectomy and oropharyngeal carcinoma was analyzed by time since first registration of tonsillectomy. Tonsillectomy was a time-dependent variable. Individuals were censored for death, emigration, or tonsillectomy within incident year of diagnosis. Incidence rate ratios (RR) were estimated by Poisson regression models and adjusted for confounders. Kaplan-Meier survival analyses were compared by the log-rank test, and HRs were estimated by Cox proportional hazards models. From 1977 to 2012, the incidence of tonsillectomies significantly decreased, whereas the incidence of oropharyngeal carcinoma significantly increased. Tonsillectomy was not associated with risk of oropharyngeal carcinoma or malignancies of other anatomic sites, including base of tongue. However, tonsillectomy significantly reduced risk of diagnosis with tonsil carcinoma [RR, 0.40; 95% confidence interval (CI), 0.22-0.70]. The risk of diagnosis with tonsil carcinoma at age <60 years was significantly decreased (RRadj, 0.15; 95% CI, 0.06-0.41) after tonsillectomy. Tonsillectomy within 1 year of diagnosis with tonsil carcinoma was associated with significantly improved overall survival (HR, 0.53; 95% CI, 0.38-0.74). In conclusion, remote history of tonsillectomy reduces the risk of diagnosis with tonsil carcinoma. These data inform risk and benefit of tonsillectomy, a common procedure and design of secondary prevention trials. ©2015 AACR.


Peng S.,Johns Hopkins Medical Institutions | Lyford-Pike S.,Johns Hopkins Medical Institutions | Akpeng B.,Johns Hopkins Medical Institutions | Wu A.,Johns Hopkins Medical Institutions | And 4 more authors.
Cancer Immunology, Immunotherapy | Year: 2013

Although therapeutic HPV vaccines are able to elicit systemic HPV-specific immunity, clinical responses have not always correlated with levels of vaccine-induced CD8+ T cells in human clinical trials. This observed discrepancy may be attributable to an immunosuppressive tumor microenvironment in which the CD8+ T cells are recruited. Regulatory T cells (Tregs) are cells that can dampen cytotoxic CD8+ T-cell function. Cyclophosphamide (CTX) is a systemic chemotherapeutic agent, which can eradicate immune cells, including inhibitory Tregs. The optimal dose and schedule of CTX administration in combination with immunotherapy to eliminate the Treg population without adversely affecting vaccine-induced T-cell responses is unknown. Therefore, we investigated various dosing and administration schedules of CTX in combination with a therapeutic HPV vaccine in a preclinical tumor model. HPV tumor-bearing mice received either a single preconditioning dose or a daily dose of CTX in combination with the pNGVL4a-CRT/E7(detox) DNA vaccine. Both single and daily dosing of CTX in combination with vaccine had a synergistic antitumor effect as compared to monotherapy alone. The potent antitumor responses were attributed to the reduction in Treg frequency and increased infiltration of HPV16 E7-specific CD8+ T cells, which led to higher ratios of CD8+/Treg and CD8+/CD11b +Gr-1+ myeloid-derived suppressor cells (MDSCs). There was an observed trend toward decreased vaccine-induced CD8+ T-cell frequency with daily dosing of CTX. We recommend a single, preconditioning dose of CTX prior to vaccination due to its efficacy, ease of administration, and reduced cumulative adverse effect on vaccine-induced T cells. © 2012 Springer-Verlag.


Liu J.,University of Pittsburgh | Ferris R.L.,University of Pittsburgh | Ha P.K.,Milton nce Jr Head And Neck Center
Head and Neck | Year: 2012

Background. Adenoid cystic carcinoma (ACC) is an unusual salivary gland malignancy that remains poorly understood. Standard treatment, including surgery with postoperative radiation therapy, has attained reasonable local control rates, but the propensity for distant metastases has limited any improvement in survival over time. Our understanding of the molecular mechanisms driving ACC is quite rudimentary, due to the infrequent nature of its occurrence. Methods. An extensive literature review was performed on salivary gland ACCs and basic science research findings. Results. This review highlights many findings that are emerging about the carcinogenesis of ACC including cytogenetics, tumor suppressor genes, oncogenes, epigenetic alterations, mitochondrial alterations, and biomarker studies. Conclusion. Although there have been many discoveries, much still remains unknown about this rare malignancy. © 2011 Wiley Periodicals, Inc.


Guo T.,Johns Hopkins Medical Institutions | Rettig E.,Johns Hopkins Medical Institutions | Fakhry C.,Johns Hopkins Medical Institutions | Fakhry C.,Milton nce Jr Head And Neck Center
Oral Oncology | Year: 2016

Objectives: Human papillomavirus (HPV)-positive tumor status is associated with improved prognosis after disease recurrence in oropharyngeal squamous cell carcinoma (OPSCC). In this study the potential role of survival bias in the relationship between HPV tumor status and the timing of recurrence was evaluated, given conflicting evidence in the literature. Materials & methods: A secondary analysis was performed on a previously published retrospective two institution study of recurrent OPSCC with known HPV tumor status. Patients were categorized as "early" (surviving "24 months) or "late" survivors (P24 months). Timing of first recurrence and overall survival were analyzed using Kaplan-Meier and cox proportional hazard methods. Two-sided p-values >0.05 were considered significant. Results: In total 101 patients met criteria including 81 late and 20 early survivors. HPV-positive tumor status was associated with longer time to recurrence in late survivors (median 21.8 vs. 13.8 months, p = 0.028). Late survivors had later recurrences in HPV-positive (p > 0.001) and HPV-negative patients (p = 0.0096), as well as in both locoregional (p > 0.0001) and distant metastatic recurrence (p > 0.0001). In multivariate analysis, both HPV-positive tumor status (adjusted HR [aHR] 0.48, p = 0.006) and survival beyond 24 months (aHR 0.21, p " 0.001) were associated with later recurrence. When stratified, HPV tumor status was only associated with later recurrence in late survivors (aHR 0.47, p = 0.015). Conclusions: Late survivorship was associated with late recurrence for both HPV-positive and HPVnegative patients. Stratification by survival illustrates how survival bias links late survivorship with late recurrences and contributes to our understanding of the impact of HPV tumor status on the timing of recurrence. © 2015 Elsevier Ltd. All rights reserved.


Shikani A.H.,Otolaryngology Head and Neck Surgery | Shikani A.H.,Johns Hopkins Hospital | Dietrich-Burns K.,Milton nce Jr Head And Neck Center
International Forum of Allergy and Rhinology | Year: 2012

Background: The objective of this work was to obtain a controlled subjective and objective in vivo clinical comparison of the Passy-Muir, Shiley, and Ball speaking valves. Methods: Ten patients free of laryngeal pathology but dependent on tracheotomy for respiration were tested with each of the speaking valves. Olfaction was assessed for each patient using the University of Pennsylvania Smell Identification Test (UPSIT). Acoustic and perceptual analyses included subjective assessments, noninstrumental objective assessments (including maximum phonation time, and S:Z ratio), and instrumental objective assessments (including fundamental frequency:maximum phonation range, vocal intensity, perturbation, naturalness, and turbulence). Oxygen saturation was assessed by pulse oximetry. Results: There was a highly significant statistical difference in olfaction and speech naturalness, in favor of the Ball valve (The Airway Company, Forest Hill, MD). The Ball valve's speech parameters were generally better than with the Passy-Muir and Shiley valves, including maximum phonation, S:Z ratio, jitter, noise, and turbulence, although the differences were not statistically significant. There were no differences among the valves in oxygen saturation levels. Conclusion: This study illustrates that olfaction and certain speech parameters, most noticeably speech naturalness, are significantly improved with the Ball valve as compared to the Passy-Muir and Shiley valves. © 2012 ARS-AAOA, LLC. Copyright © 2012 American Rhinologic Society-American Academy of Otolaryngic Allergy, LLC.

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