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Cancers of the head and neck region often present with nodal involvement. There is a long-standing convention within the community of head and neck radiation oncology to irradiate both sides of the neck electively in almost all cases to include both macroscopic and microscopic disease extension (so called elective nodal volume). International guidelines for the selection and delineation of the elective lymph nodes were published in the early 2000s and were updated recently. However, diagnostic imaging techniques have improved the accuracy and reliability of nodal staging and as a result, small metastases that used to remain undetected and were thus in the past included in the elective nodal volume, will now be included in high-dose volumes. Furthermore, the elective nodal areas are situated close to the parotid glands, the submandibular glands and the swallowing muscles. Therefore, irradiation of a smaller, more selected volume of the elective nodes could reduce treatment-related toxicity. Several researchers consider the current bilateral elective neck irradiation strategies an overtreatment and show growing interest in a unilateral nodal irradiation in selected patients. The aim of this article is to give an overview of the current evidence about the indications and benefits of unilateral nodal irradiation and the use of SPECT/CT-guided nodal irradiation in squamous cell carcinomas of the head and neck., (© 2021 Wiley Periodicals LLC.)

Introduction: Our purpose is to review the role radiotherapy (RT) in the treatment of glottic squamous cell carcinoma (SCC)., Methods: A concise review of the pertinent literature., Results: RT cure rates are Tis- T1N0, 90% to 95%; T2N0, 70% to 80%; low-volume T3-T4a, 65% to 70%. Concomitant cisplatin is given for T3-T4a SCCs. Severe complications occur in 1% to 2% for Tis-T2N0 and 10% for T3-T4a SCCs. Patients with high-volume T3-T4 SCCs undergo total laryngectomy, neck dissection, and postoperative RT. Those with positive margins and/or extranodal extension receive concomitant cisplatin. The likelihood of local-regional control at 5 years is 85% to 90%. Severe complications occur in 5% to 10%., Conclusions: RT is a good treatment option for patients with Tis-T2N0 and low-volume T3-T4a glottic SCCs. Patients with higher volume T3-T4 cancers are best treated with surgery and postoperative RT., (© 2020 Wiley Periodicals LLC.)

HPV-related (HPV+) oropharyngeal cancer (OPC) has a better prognosis compared to HPV unrelated (HPV-) OPC. This review summarizes and discusses several of the controversies regarding the management of HPV+ OPC, including the mechanism of its treatment sensitivity, modern surgical techniques, chemotherapy regimens, and treatment de-intensification protocols. We also discuss and reconsider potential adverse prognostic factors such as tumor EGFR expression, tumor hypoxia, and patient smoking history, as well as the significance of retropharyngeal adenopathy. Finally, we discuss elective nodal treatment of uninvolved lymph node stations. While this review does not exhaust all controversies related to the management of HPV+ OPC, it aims to highlight some of the most clinically relevant ones.

Background: This study provides Australian data on the characteristics of human papillomavirus (HPV)-related oropharyngeal squamous cell carcinoma (SCC) over the last 2 decades., Methods: The HPV status of 515 patients with oropharyngeal SCC diagnosed between 1987 and 2010 was determined by HPV E6-targeted multiplex real time polymerase chain reaction assay (PCR) and p16 immunohistochemistry., Results: The HPV positivity rate increased from 20.2% (1987-1995) to 63.5% (2006-2010). Among HPV-positive oropharyngeal SCC over the study period, the median age increased from 55.4 years to 59.8 years (p = .004) and there was a trend of an increasing proportion of never smokers (19.2% to 34.0%). The use of radiation therapy (RT) in patients with HPV-positive oropharyngeal cancer increased from 26.9% to 68.1% (p = .007) and we also observed a trend of improved outcomes., Conclusion: Our data show a rising prevalence of HPV-positive oropharyngeal SCC in Australia over the last 2 decades. These patients with HPV-positive oropharyngeal SCC are now presenting at an older age and about one third have never smoked., (© 2015 Wiley Periodicals, Inc.)

Background: The optimal cumulative dose and timing of cisplatin administration in various concurrent chemoradiotherapy protocols for nonmetastatic head and neck squamous cell carcinoma (HNSCC) has not been determined., Methods: The absolute survival benefit at 5 years of concurrent chemoradiotherapy protocols versus radiotherapy alone observed in prospective randomized trials reporting on the use of cisplatin monochemotherapy for nonnasopharyngeal HNSCC was extracted. In the case of nonrandomized studies, the outcome results at 2 years were compared between groups of patients receiving different cumulative cisplatin doses., Results: Eleven randomized trials and 7 nonrandomized studies were identified. In 6 definitive radiotherapy phase III trials, a statistically significant association (p = .027) between cumulative cisplatin dose, independent of the schedule, and overall survival benefit was observed for higher doses., Conclusion: Results support the conclusion that the cumulative dose of cisplatin in concurrent chemoradiation protocols for HNSCC has a significant positive correlation with survival. © 2015 Wiley Periodicals, Inc. Head Neck 38: E2151-E2158, 2016., (© 2015 Wiley Periodicals, Inc.)

It is now clear that the two separate entitles of tonsillar cancer, HPV induced and non-HPV induced (smoking induced), have significantly different presenting stage and outcomes. A significant proportion of patients with human papillomavirus positive tonsillar cancer have had exposure to smoking. We examined the combined effect of human papillomavirus and smoking on the outcomes and determined whether smoking can modify the beneficial effect of human papillomavirus. A total of 403 patients from nine centers were followed up for recurrence or death for a median of 38 months. Determinants of the rate of loco-regional recurrence, death from tonsillar cancer and overall survival were modeled using Cox regression. Smoking status was a significant predictor of overall survival (p = 0.04). There were nonstatistically significant trends favoring never smokers for loco-regional recurrence and disease specific survival. In addition, there was no statistically significant interactions between smoking and human papillomavirus (p-values for the interaction were 0.26 for loco-regional recurrence, 0.97 for disease specific survival and 0.73 for overall survival). The effect of smoking on loco-regional recurrence and disease specific survival outcomes was not statistically significant, nor was there significant evidence that the effect of smoking status on these outcomes was modified by HPV status. Irrespective of HPV status, however, smokers did have poorer overall survival than never-smokers, presumably due to effects of smoking that are unrelated to the primary cancer., (Copyright © 2012 UICC.)

Objectives: Second primary tumors (SPTs) have been implicated in poor overall survival (OS) of head and neck squamous cell carcinomas (HNSCCs). Confusion remains regarding their actual incidence and prognostic impact. This study assessed the incidence of SPTs; the SPT diagnostic time lag; the impact on OS; and the mean annual risk., Methods: Nine hundred eighty seven consecutive patients treated for primary larynx SCC (1967-2004) were analyzed in this study. 96.3% and 91.4% of patients reached a minimum follow-up period of 3 and 5 years., Results: Two hundred eight (21.1%) patients were diagnosed with SPTs. One hundred forty three (14.5%) patients developed upper aero-digestive tract (UAD)-SPTs, 83 (8.4%) were HNSCCs, 56 (5.7%) were lung, and 4 (0.41%) were esophageal-SPTs. Survival analysis demonstrated clear superior OS rates for the UAD-SPT (P < 0.008) and HNSCC-SPT (P < 0.001) groups. A comparison of survival of subgroups showed lung/esophagus to have a poorer survival when compared to all other subgroups. OS after diagnosis of an SPT was poorer when compared with no-SPT group (P < 0.001). The mean annual risk of developing UAD-SPTs was 2.4%., Conclusion: These results suggest that HNSCC-SPT should not be viewed as an adverse prognostic factor. Reclassifications of UAD-SPTs into HNSCC-SPT and non-HNSCC-SPT better reflects their clinical behavior and prognosis.

Oral Squamous Cell Carcinoma (OSCC) remains a public health scourge. Radiotherapy (RT) is a major treatment modality and has been implicated in possible formation of Second Primary Tumours (SPT). In a single centre retrospective study of 370 patients with OSCCs (1967-2004) associations between RT, diagnosis of SPTs, median SPT diagnostic time lag, Disease Free Survival (DFS) and overall survival (OS) were analysed. Sixty-eight (18.4%) patients developed metachronous SPTs. Two hundred and twenty patients (59.3%) underwent some form of RT whilst 151 (40.7%) patients were not exposed to RT. No significant increased incidence of SPTs was demonstrated in the RT group. No significant difference in SPT diagnostic time lag was noted amongst the groups. This study suggests that RT is neither a risk for SPT induction nor increases the relative diagnostic time delay of upper aero-digestive tract SPTs.

Background: Field cancerization is a feature of HNSCCs. No biological marker in the index tumor has correlated with second primary tumor (SPTs) development. Changes in MDM-2 and epidermal growth factor receptor (EGFR) expression are known to be early neoplastic changes in HNSCC. EGFR expression is correlated with clinical outcomes. This study has assessed the predictive correlation of MDM-2 and EGFR protein expression with clinicopathological parameters and occurrence of SPTs in HNSCC., Methods: Using immunohistochemistry, 106 patients who were treated for primary laryngeal squamous cell carcinoma were investigated for expression of MDM-2 and EGFR., Results: Positive expression of MDM-2 and EGFR was found in 51 of 106 (48.1%) and 82 of 106 (77.4%) cases, respectively. EGFR expression was found to correlate with diagnosis of new primary tumors (P = 0.003), disease-free survival (P = 0.008), as well as overall survival (P = 0.003). MDM-2 expression correlated with nodal relapse (P = 0.03)., Conclusions: SPTs relate to poor prognosis in HNSCC, indicating that closer clinical surveillance of this patient group would be beneficial. Examination of the expression of EGFR by the primary tumor could have potential clinical benefits because this study suggests that it may become a vital biomarker for patients who are most at risk of developing SPTs.

Aims: Larynx cancer is the most common form of head and neck squamous cell carcinoma (HNSCC). Radiotherapy is a major treatment modality and is implicated in the possible formation of second primary tumours (SPT). The aims of this retrospective study were to establish the incidence of SPTs and their correlation with previous radiotherapy and to establish overall survival and the SPT diagnostic time lag from the index tumour according to subtype as well as radiotherapy status., Materials and Methods: In a retrospective study of 987 patients with larynx SCCs (1967-2004) associations between radiotherapy, diagnosis of SPTs, median SPT diagnostic time lag, disease-free survival and overall survival were analysed., Results: In total, 184 (18.6%) patients developed metachronous SPTs with an overall survival of 93.0 (standard error 6.8 months). One hundred and seventy (92.4%) underwent radiotherapy, whereas 14 (7.6%) patients were not exposed to radiotherapy. No significant increased incidence of SPT was shown in the radiotherapy group. A statistically non-significant increase in SPT diagnostic time lag trend was noted for both HNSCC SPTs (radiotherapy vs non-radiotherapy; 76.0 [standard error 6.7] vs 50.0 [standard error 23.0]) and lung SPTs (45.0 [standard error 12.1] vs 24.0 [standard error 4.9]) months., Conclusion: This study suggests that radiotherapy is not a risk for SPT induction; it may, however, neutralise a proportion of cancerised fields in the lung and head and neck areas without any significant benefit on overall survival.

Background: Field cancerization is a feature of head and neck squamous cell carcinoma. No biological marker in the index tumour has been correlated to the development of second primary tumours (SPT). Cyclin A1 is a cell cycle regulator and a downstream target of p53. This study assessed predictive correlation of cyclin A1 and mut-p53 with clinicopathological parameters and occurrence of (SPT) in the head and neck., Methods: Using immunohistochemistry 106 patients treated for primary laryngeal squamous cell carcinoma were investigated for expression of cyclin A1 and mut-p53., Results: Expression of cyclin A1 and mut-p53 were noted in 83 of 106 (78.3%) and 25 of 106 (23.6%) patients. There was a weak but significant correlation between mut-p53 and cyclin A1 (r = 0.301, P = 0.002) expression. During the follow-up period (median 41.0 months (range 1-205 months)), 21 of 106 (19.8%) patients developed an SPT. There was no statistically significant correlation between the markers investigated and disease recurrence, SPT diagnosis or clinicopathological parameters., Conclusion: Second primary tumours are an intriguing problem in treatment of HNSCC and a predictive marker identifying those greatest at risk would be a leap forward.

Aims: To evaluate a single centre's experience with subglottic laryngeal carcinoma., Materials and Methods: The laryngeal cancer database at the Prince of Wales Hospital was sourced to define a sub-population of patients presenting with primary subglottic carcinoma. Excluded from the analysis were patients having a glottic origin for their carcinoma and secondarily involving the subglottis., Results: Of 969 patients with newly diagnosed laryngeal cancer, 10 (1%) had subglottic origin. T stage was six T2 and four T3, all were N0. A total laryngectomy was carried out in five patients, four of whom had postoperative radiotherapy, a hemilaryngectomy in one patient and definitive radiotherapy in four patients. There was only one local failure, who could not be salvaged, and one patient died locally controlled with metastatic disease. Thus, local control was achieved in nine of 10 patients., Conclusion: Although an infrequent sub-population, subglottic carcinoma has a high likelihood of being locally controlled.

Perineural invasion resulting in leptomeningeal carcinomatosis is a rare, but well-recognized phenomenon in head and neck carcinomas. We report the rare case of a patient with a squamous cell carcinoma of the lip resulting in leptomeningeal carcinomatosis and review the relevant published work. A 51-year-old man presented with progressive facial paraesthesia after treatment for a recurrent squamous cell carcinoma of the lower lip. Cavernous sinus involvement was confirmed on MRI and he received stereotactic radiotherapy. He subsequently developed progressive lower limb neurological signs. An MRI showed multiple enhancing leptomeningeal nodules in the cervical and lumbar spine consistent with leptomeningeal carcinomatosis. Whole spine radiotherapy and dexamethasone resulted in short-term stabilization of symptoms only and he rapidly succumbed to progressive neurological disease. To our knowledge, this is the first published report of a squamous cell carcinoma of the lip resulting in leptomeningeal disease of the cauda equina. It illustrates the potential aggressive natural history of squamous cell carcinomas with perineural invasion.

The purpose of the present paper was to review the results of treating early (stages T1-2N0) glottic, squamous cell carcinoma by radiotherapy in the Department of Radiation Oncology, Prince of Wales Hospital, Sydney. A retrospective review was carried out of all patients seen in the department from 1967 to 1994, inclusive. To be eligible, patients had to have newly diagnosed cancer and to have been treated with curative intent by radiotherapy alone. Three hundred and sixty-nine patients satisfied the eligibility requirements. The mean follow-up time was 12.2 years (maximum: 28 years). At 5 years the actuarial local control rate was 80% (84% for stage T1 and 72% for T2). The ultimate local control rate was 96%. The overall survival rates at 5 and 10 years were 73% and 52%, respectively. The risk of nodal recurrence was much higher after persisting disease or local recurrence. Our results confirm the high cure rates achieved with this modality of treatment and are comparable with those reported in the literature.

Purpose: To retrospectively assess a protocol of split-course accelerated radiation therapy (SCAT) for selected head and neck cancers., Methods and Materials: SCAT consisted of 1.8 Gy per fraction administered twice daily with a minimum gap between fractions of 6 h. The treatment protocol prescribed an initial 16 fractions followed by a planned 5 to 12 day break, and then a further 20 to 22 fractions for a total dose ranging from 64.8 to 72 Gy delivered in 5 to 6 weeks., Results: Twenty-eight patients received SCAT for histologically confirmed head and neck cancer between January 1987 and August 1991. All patients were followed up until December 1, 1993. The mean potential follow-up time was 4.2 years (range: 2.9-6.2 years). All patients completed the treatment protocol. Thirteen tumors were laryngeal in origin, eight hypopharyngeal, four paranasal sinus, and three oropharyngeal. There were no Stage I, three Stage II, nine Stage III, and 12 Stage IV tumors. Four tumors were not staged (two paranasal sinus cancers and two surgical recurrences). Early and late toxicities were moderate to severe. Confluent mucositis was experienced by 27 of the 28 patients (96%). One patient required a prolonged midtreatment break of 24 days. Nine patients (32%) required narcotic analgesia for pain relief. Eleven patients (39%) required hospitalization for nasogastric feeding or pain control. The median length of hospital stay was 14 days (range 7-98 days). The actuarial rate of severe late toxicity at 3 years was 47% (standard error (SE) = 13%). A complete tumor response was achieved in 86% of patients. The actuarial local control rate at 3 years was 43% (SE = 11%) and the actuarial survival rate at 3 years was 25% (SE = 8%)., Conclusion: Given the encouraging complete response rate and local control for such advanced tumors, SCAT for locoregionally advanced tumors merits further investigation. However, because of the significant late toxicity observed, the total dose, interfraction interval, and fractionation technique used should be reconsidered.