Clinical immunotherapeutic approaches for the treatment of head and neck cancer

Head and neck squamous cell carcinoma (HNSCC) is the sixth most common malignancy worldwide, accounting for more than 550,000 cases and 380,000 deaths annually. The primary risk factors associated with HNSCC are tobacco use and alcohol consumption; nevertheless genetic predisposition and oncogenic viruses also play important roles in the development of these malignancies. The current treatments for HNSCC patients include surgery, chemotherapy, radiotherapy, and cetuximab, and combinations of these. However, these treatments are associated with significant toxicity, and many patients are either refractory to the treatment or relapse after a short period. Despite improvements in the treatment of patients with HNSCC, the clinical outcomes of those who have been treated with standard therapies have remained unchanged for over three decades and the 5-year overall survival rate in these patients remains around 40–50%. Therefore, more specific and less toxic therapies are needed in order to improve patient outcomes. The tumour microenvironment of HNSCC is immunosuppressive; therefore immunotherapy strategies that can overcome the immunosuppressive environment and produce long-term tumour immunosurveillance will have a significant therapeutic impact in these patients. This review focuses on the current immunological treatment options under investigation or available for clinical use in patients with HNSCC.     

Salvage surgery for recurrent carcinoma of the oral cavity: assessment of prognostic factors

Salvage surgery is the most acceptable therapeutic option for disease control of loco-regional recurrences in oral cancers. Prognostic factors need to be assessed to select patients for salvage surgery who would benefit the most. This was a single-centre retrospective observational study conducted between 2015 and 2018. A total of 168 patients with recurrent oral cavity carcinoma who underwent salvage surgery were included for analysis. The primary endpoints of the study were to evaluate overall survival (rOS) after salvage surgery and prognostic factors affecting survival. In this study, the median rOS was 18 months and the median disease-free survival (rDFS) was 14 months. Advanced stage (hazard ratio (HR) 2.387, 95% confidence interval (CI) 1.496–3.808; P = 0.001) and multimodality treatment (HR 1.642, 95% CI 1.139–2.367; P = 0.008) in the initial disease, as well as nodal spread (HR 3.794, 95% CI 1.580–9.111; P = 0.008) and perineural invasion (HR 2.167, 95% CI 1.358–3.455; P = 0.001) in the recurrent disease, were found to adversely affect survival after salvage surgery. With thorough assessment of the prognostic factors and appropriate patient selection, survival may be favourable after salvage surgery for recurrent oral cavity carcinoma.     

Specimen‐driven intraoperative assessment of resection margins should be standard of care for oral cancer patients

With an incidence of 350.000 new cases per year, cancer of the oral cavity ranks among the 10 most common solid organ cancers. Most of these cancers are squamous cell carcinomas. Five‐year survival is about 50%. It has been shown that clear resection margins (>5 mm healthy tissue surrounding the resected tumor) have a significant positive effect on locoregional control and survival. It is not uncommon that the resection margins of oral tumors are inadequate. However, when providing the surgeon with intraoperative feedback on the resection margin status, it is expected that obtaining adequate resection margins is improved. In this respect, it has been shown that specimen‐driven intraoperative assessment of resection margins is superior to defect‐driven intraoperative assessment of resection margins. In this concise report, it is described how a specimen‐driven approach can increase the rate of adequate resections of oral cavity squamous cell carcinoma as well as that it is discussed how intraoperative assessment can be further improved with regard to the surgical treatment of oral cavity squamous cell carcinoma.     

Clinical comment of programmed cell death protein 1 immunotherapy for advanced head and neck cancer

程序性细胞死亡蛋白1（PD-1）单抗是近年来恶性肿瘤治疗领域具有里程碑意义的药物,PD-1单抗的出现使免疫治疗迅速成为各种恶性肿瘤治疗的新选择。国外大量临床研究已充分证实其在晚期头颈癌的治疗中具有较传统治疗方案更加显著的疗效,同时具有低于细胞毒性药物的不良反应发生率。近期PD-1单抗类药物进入我国临床应用,改变了传统头颈部恶性肿瘤的治疗模式,免疫治疗已经成为复发/转移晚期头颈癌的一线治疗选择。目前,PD-1单抗类药物通过临床试验对其适应证进行不断拓展,同时也在对其生物标志物进行探索和验证。随着研究不断深入,PD-1单抗类药物的应用将趋于个体化、精准化,与传统疗法的联合应用有待临床进一步大样本多中心随机研究的印证。     

Radiotherapy-induced oral morbidities in head and neck cancer patients

The cumulative effect of radiation and the extent of related morbidities on oral tissues are enormous and increase over time. The numerous radiation-related side effects have a strong, negative influence on the oral functions and are responsible for a drastic reduction in the oral-health-related quality of life of the cancer survivors. In a significant deviation to the earlier approach of advising extraction of all remaining teeth before RT, the concept of preserving a maximum number of teeth in a state of health and for better oral functions postcancer cure has been globally accepted and is adhered to. The effects of radiation and their impact on the general well-being of the patients underscore the relevance of understanding the sequelae of radiation therapy on healthy oral tissues, preexisting oral diseases and their progression, impact on oral treatment needs, limitations in performing the indicated treatment, and shortcoming in treatment outcomes. It is vital for the professionals involved in head and neck cancer care to follow a well-devised referral system for oral care before and after RT and educate patients for a life-long follow-up     

Prognostic value of lymph node count from selective neck dissection in oral squamous cell carcinoma

Unlike the levels of anatomical exploration, there is no consensus on the extent of lymph node dissection, or lymph node count (LNC), during selective neck dissection (SND). The aim of this study was to validate the prognostic impact of LNC on survival and to determine an optimal LNC cut-off value for SND. A retrospective investigation identified 78 patients with a diagnosis of oral squamous cell carcinoma (OSCC) who underwent SND (levels I–III or levels I–IV). LNC and clinicopathological variables were analyzed for any association with survival in Cox proportional hazards models. Based on the receiver operating characteristic curve, a cut-off value of 19 lymph nodes was found to predict overall survival (OS) (area under the curve 0.732, sensitivity 67.8%, specificity 75.0%; P = 0.026) and disease-specific survival (DSS) (area under the curve 0.762, sensitivity 68.1%, specificity 77.8%; P = 0.011). On Cox regression, LNC (≥19 vs. <19) was the only independent predictor of OS (hazard ratio 5.29, 95% confidence interval 1.39–20.05; P = 0.014) and DSS (hazard ratio 6.76, 95% confidence interval 1.40–32.77; P = 0.018). Similar results were obtained in the pathologically lymph node-negative subgroup (n = 66). Based on the study findings, SND should include 19 or more lymph nodes for a survival benefit.     

Performance and survival outcomes of defect-driven versus specimen-driven method of frozen section intraoperative margin assessment in oral cancers

Margin status is one of the most important prognostic factors in oral cancers. Intraoperative frozen section (FS) can be performed to ensure a margin-negative resection, however the method of FS assessment is debatable. The aim of this study was to compare the defect-driven (DDA) versus specimen-driven (SDA) approach for intraoperative assessment of tumour margins in oral cancer resections and their impact on loco-regional recurrence and survival. The primary study endpoint was margin status determined from the final histopathological examination report. Secondary endpoints were disease recurrence and survival. This retrospective cohort study compared the two methods of FS in terms of their performance and survival outcomes. All oral squamous cell carcinoma patients who underwent surgery as the primary treatment from January 2018 to February 2019 were included. The involved margin rate was slightly lower with SDA than DDA (7.5% vs 11.8%), however the difference was not statistically significant. The recurrence rate was higher with DDA (19/51, 37.2%) than SDA (14/53, 26.4%), although this was not statistically significant. Local recurrence-free survival (DDA 62% vs SDA 75%; P = 0.653) and overall survival (DDA 76% vs SDA 78%; P = 0.300) at 18 months of follow-up were comparable. There was no significant difference in sensitivity or specificity of intraoperative FS for margin assessment between SDA and DDA. The type of intraoperative FS technique used did not affect loco-regional recurrence or overall survival.     

Raman spectroscopy in oral cavity and oropharyngeal cancer: a systematic review

Due to the high incidence of head and neck cancer and under-diagnosis in the early stages, non-invasive and highly accurate diagnostic tests are required for cancer detection. Recent advances in Raman spectroscopy techniques have yielded promising sensitivity and specificity results in the evaluation of cancer. The aim of this study was to investigate the potential value of Raman spectroscopy in oral cavity and oropharyngeal cancer diagnosis based on currently available scientific papers. A search of the PubMed database was performed using a specific strategy and according to the PRISMA guidelines. Raman spectroscopy achieved a maximum accuracy of 98% in cancer detection, while accuracy was 97.24% for tumour grading evaluation, 95% for cancer treatment assessment, and 77% for the detection of cancer recurrence. Moreover, early-stage cancer can be identified by Raman spectroscopy investigation of liquid biopsy samples. An in vivo technique with direct mucosa examination by fibre-optic Raman spectroscopy obtained a maximum accuracy of 94% in cancer diagnosis. The most prominent markers of the presence of malignancy were an increase in Raman signal intensity for proteins, nucleic acids, and water and a decrease for lipids. These cancer discriminants were detected in both fingerprint and high wavenumber regions. In conclusion, Raman spectroscopy is a promising tool for oral cavity and oropharyngeal cancer screening.     

Wnt pathway in oral cancer: A review update

The Wnt signalling pathway involves in the pathogenesis of human diseases and one of the pathways that contribute to embryogenic development. Studies about the Wnt pathway have unfolded its regulation in many cancer cell mechanisms such as cell survival, migration, polarity, and cell multiplication. Moreover, the Wnt pathway has a significant role in cell fate determination and self-renewal in stem cells. Oral cancer shares significant concern among clinicians and researchers. However, there are only a few studies done on oral cancer and its correlation with the Wnt pathway. The expression of Wnt gene members in many malignancy diseases which included oral cancer has proven a high inverse correlation with malignancy diseases and malignancy progression. Metastasis which predominantly occurred through the lymphatic system has been the principal cause of mortality in oral cancer and affected to cancer stage, main tumour site, cancer cell differentiation and cancer cell adhesion potency. With intention of contributing to oral pathology and oral medicine research and knowledge advancement, particularly in the oral cancer area, this article presents current findings regarding the Wnt pathway and its multiple mechanisms associated with the treatment of oral carcinogenesis through Wnt pathway signalling.     

Review of outcomes of 500 consecutive cases of non-melanoma skin cancer of the head and neck managed in an oral and maxillofacial surgical unit in a District General Hospital

We provide a non-melanoma skin cancer (NMSC) service for skin cancers of the head and neck in the south-west of England. We hypothesised that certain anatomical sites such as the nose and eyelid would have a higher incidence of close or involved margins than others, and that the choice of repair might influence the excised margins. We therefore retrospectively analysed the data of 500 consecutive NMSC that were operated on in the oral and maxillofacial surgery unit of Taunton and Somerset NHS Trust. The database reports were crosschecked against the Trust’s own pathology reporting system to ensure that they were accurate. Data collected included clinical and personal details of patients, anatomical sites, type of reconstruction, histopathological diagnosis, excision margins, and complications. Of the 500 patients reviewed 362 (72%) were basal cell carcinomas (BCC) and 138 (28%) squamous cell carcinomas (SCC). The outcomes of 243 patients treated by primary closure, 134 treated by reconstruction with local flaps, and 123 treated by skin grafts, were reviewed with particular attention paid to the anatomical site and excision margins. There was an overall incomplete excision rate of 10.8% (n = 54) and 29 patients developed complications (5.8%). We confirmed that rates of close or incomplete margins are more likely in certain anatomical sites such as the nose, forehead, and ear. The rate of involved margins was unaffected by choice of surgical technique.     

Hyalinizing clear cell carcinoma of salivary gland origin in the head and neck: clinical and histopathological analysis

Hyalinizing clear cell carcinoma (HCCC) is an extremely rare neoplasm of salivary gland origin with a low-grade indolent nature. It is difficult to distinguish from other malignant salivary gland tumours. Clinical outcomes following surgery are generally reported as good. The aim of this study was to further determine the features of HCCC. This study was approved by Medical ethics review of affiliated hospital of jiangsu university. Fourteen new cases of HCCC are reported. The clinical and histopathological data of these 14 cases were analysed alongside those of 141 cases identified in a systematic review of the literature (up to 2016). Demographic data, histopathological findings, clinical presentation, primary treatment, and outcomes were extracted. Histologically, HCCC tumour cells had a clear cell morphology with hyalinized stroma. Immunohistochemical results were positive for cytokeratins and EMA, but negative for SMA, S100, vimentin, and calponin. Twelve of the 14 patients showed EWSR1 translocation. Local nodal metastasis on presentation was present in 17.3% and the overall recurrence rate was 17.7% in the total population (N = 155), compared with 35.7% and 21.4%, respectively, in the new cases alone. Focal necrosis and local metastasis were identified as possibly associated with recurrence. The overall prognosis was good: only 3.8% of patients died of the disease. HCCC is less indolent than was previously thought, but overall the prognosis is good. Risk factors for recurrence may include focal necrosis and local metastasis at presentation. The best treatment for patients with HCCC is wide local excision combined with regional lymph node dissection.