Clinical characteristics and outcomes of oropharyngeal carcinoma related to high-risk non-human papillomavirus16 viral subtypes.

BACKGROUND: The majority of human papillomavirus (HPV)-related oropharyngeal carcinomas (OPCs) are associated with HPV genotype 16; however, OPC can be associated with other high-risk non-HPV16 genotypes. METHODS: This was a retrospective analysis of patients with high-risk non-HPV16 OPC treated at a single tertiary institution. Sociodemographic and clinical information was obtained by chart review. HPV genotype was determined by polymerase chain reaction (PCR). Baseline data and outcomes were compared between HPV16 and high-risk non-HPV16 groups. RESULTS: High-risk non-HPV16 genotypes accounted for 9% of HPV-related OPC. Of the 27 total high-risk non-HPV16 OPCs, HPV35 was most prevalent (48%). High-risk non-HPV16 OPC presented at a slightly higher age (p = .021) and higher clinical T classification (p = .008) compared to HPV16 OPC, but there was no significant survival difference. CONCLUSION: Clinical characteristics of high-risk non-HPV16 OPC were largely consistent with those of HPV16 OPC. Additional multi-institutional studies will be required to demonstrate conclusively that the favorable prognosis of patients with HPV16 applies to all high-risk HPV types. © 2016 Wiley Periodicals, Inc. Head Neck 38: 1330-1337, 2016.

Operative margin control with high-resolution optical microendoscopy for head and neck squamous cell carcinoma.

OBJECTIVES/HYPOTHESIS: High-resolution microendoscopy (HRME) provides real-time visualization of the mucosal surface in the upper aerodigestive tract. This technology allows noninvasive discrimination of benign and neoplastic epithelium and has potential applications for intraoperative margin detection. STUDY DESIGN: Single institution, prospective, feasibility trial (phase I) of in vivo optical imaging. METHODS: The study was conducted on patients with squamous cell carcinoma of the upper aerodigestive tract. High-resolution microendoscopy images obtained during surgery were correlated with histopathologic diagnosis to determine the ability of HRME to differentiate between benign and malignant mucosa. Blinded reviewers evaluated HRME images and made determinations of the status of the mucosa. Accuracy, sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and interrater agreement between multiple raters were calculated to determine the accuracy of HRME imaging. RESULTS: The mean accuracy of reviewers in differentiating neoplastic or benign mucosa was 95.1% (95% confidence interval [CI], 94%-96%). Sensitivity and specificity were 96% (95% CI, 94%-99%) and 95% (95 % CI, 90%-99%), respectively. The NPV was 98% (95% CI, 97%-99%), and PPV was 91% (95% CI, 85%-98%). The Fleiss kappa statistic for interrater reliability was 0.81, with a standard error of 0.014 and a 95% CI (0.78-0.84). CONCLUSION: High-resolution microendoscopy allows real-time discrimination between benign and neoplastic mucosa. High levels of sensitivity and specificity can be obtained with this technology when interrogating mucosal surfaces. Despite several technical limitations, HRME shows promise as a technique for intraoperative margin control and platform for molecular imaging technologies. LEVEL OF EVIDENCE: 3b.

Feasibility of transoral robotic-assisted high-resolution microendoscopic imaging of oropharyngeal squamous cell carcinoma.

BACKGROUND: Transoral robotic-assisted oncologic surgery of the head and neck offers promising functional results. Nonetheless, the efficacy of oncologic surgery remains critically dependent on obtaining negative margins. We aimed to integrate a miniaturized high-resolution fiber-optic microendoscope (HRME), which provides real-time histological assessment, with the da Vinci robotic system (Intuitive Surgical, Sunnyvale, CA). METHODS: Three patients undergoing transoral robotic surgery (TORS) were prospectively enrolled in this study. Optical imaging of the oropharynx was performed intraoperatively with the robotic-assisted HRME. RESULTS: All patients underwent the procedure successfully with no complications. The HRME was successfully integrated with the da Vinci robotic system. Several sites of the oropharynx and associated malignancy were imaged, which correlated with the standard histopathological analysis. CONCLUSION: Transoral robotic-assisted HRME imaging of the oropharynx is a safe and technically feasible approach, providing a real-time histological assessment and may serve as a valuable aid in oncologic surgery.

Transoral robotic excision of ectopic lingual thyroid: Case series and literature review.

BACKGROUND: Surgical excision of an ectopic lingual thyroid has traditionally been associated with significant morbidity and has therefore been reserved for patients with severe obstructive symptoms or suspected malignancy. Transoral robotic surgery (TORS) has provided a minimally invasive approach to completely and safely excise ectopic lingual thyroid. METHODS: Three index cases were identified from the detailed clinical database of TORS patients. A systematic review of the management of ectopic lingual thyroid in the English literature was performed. RESULTS: TORS-assisted excision of a lingual thyroid gland was successfully performed in 3 patients with excellent functional outcomes CONCLUSION: TORS-assisted excision of an ectopic lingual thyroid is a safe and feasible treatment modality with minimal morbidity, and, in experienced hands, should be offered as a valid treatment for this pathology.

Chemoradiotherapy-induced upregulation of PD-1 antagonizes immunity to HPV-related oropharyngeal cancer.

While viral antigens in human papillomavirus (HPV)-related oropharyngeal cancer (HPVOPC) are attractive targets for immunotherapy, the effects of existing standard-of-care therapies on immune responses to HPV are poorly understood. We serially sampled blood from patients with stage III-IV oropharyngeal cancer undergoing concomitant chemoradiotherapy with or without induction chemotherapy. Circulating immunocytes including CD4(+) and CD8(+) T cells, regulatory T cells (Treg), and myeloid-derived suppressor cells (MDSC) were profiled by flow cytometry. Antigen-specific T-cell responses were measured in response to HPV16 E6 and E7 peptide pools. The role of PD-1 signaling in treatment-related immunosuppression was functionally defined by performing HPV-specific T-cell assays in the presence of blocking antibody. While HPV-specific T-cell responses were present in 13 of 18 patients before treatment, 10 of 13 patients lost these responses within 3 months after chemoradiotherapy. Chemoradiotherapy decreased circulating T cells and markedly elevated MDSCs. PD-1 expression on CD4(+) T cells increased by nearly 2.5-fold after chemoradiotherapy, and ex vivo culture with PD-1-blocking antibody enhanced HPV-specific T-cell responses in 8 of 18 samples tested. Chemoradiotherapy suppresses circulating immune responses in patients with HPVOPC by unfavorably altering effector:suppressor immunocyte ratios and upregulating PD-1 expression on CD4(+) T cells. These data strongly support testing of PD-1-blocking agents in combination with standard-of-care chemoradiotherapy for HPVOPC.

The role of inflammation in head and neck cancer.

Cancer-related inflammation is considered the "seventh hallmark of cancer"; numerous studies demonstrate that tumors develop and progress within inflammatory diseases. Central to the development of cancer are genetic changes that endow these cancer cells with many of the hallmarks of cancer, such as self-sufficient growth and resistance to anti-growth and pro-death signals. However, while the genetic changes that occur within cancer cells themselves, such as activated oncogenes or dysfunctional tumor suppressors, are responsible for many aspects of cancer development, they are not sufficient. Tumor promotion and progression are dependent on ancillary processes involving cells of the tumor environment that are not necessarily cancerous themselves. Infiltration of immune cells facilitates tumor development through the production of factors that promote carcinogenesis and by enabling tumors to evade the host immune response. Small molecules including cytokines, chemokines, and growth factors play key roles in both inflammation and cancer by promoting proliferation, angiogenesis, and carcinogenesis and by recruiting immune cells. The extracellular matrix is altered in inflammation and provides structural support to developing tumors. Hypoxia is a common state in cancers and inflamed tissues which causes DNA damage and induces tumorigenic factors. Finally, tissue vasculature is a vital part of its microenvironment, supplying oxygen, nutrients, and growth factors to rapidly dividing cells and providing a mechanism for metastatic spread. This review will discuss the reflexive relationship between cancer and inflammation with particular focus on how by considering the role of inflammation in physiologic processes such as the maintenance of tissue homeostasis and repair may provide a logical framework for understanding the connection between the inflammatory response and cancer. The cells and molecules outlined here represent potential targets for the treatment of head and neck cancer.