Mutation analysis of second primary tumors in head and neck cancer in Taiwanese patients through next-generation sequencing

Head and neck cancer has poor overall survival. Patients with head and neck cancer more frequently develop second primary tumors than do patients with other cancers, leading to a poor prognosis. In this study, we used next-generation sequencing to analyze and compare mutations between first tumors and second tumors in head and neck cancer. We retrieved tumor tissues collected from 15 patients who were diagnosed twice as having cancer. We used driver gene and trunk mutations to distinguish between recurrent cancer and primary cancer in oral cancer. We observed unique driver gene mutations in three patients with an initial clinical diagnosis of recurrent cancer; hence, we believe that the corresponding patients had primary cancer. Four patients with an initial clinical diagnosis of primary cancer were found to actually have recurrent cancer according to our results. Three (75%) patients with recurrent cancer demonstrated NUP98 mutations. NUP98 mutations may be a new biomarker for diagnosing recurrent oral cancer. Genetic testing can be used to enhance the accuracy of clinical diagnosis.

Treatment Modality and Second Primary Tumors of the Head and Neck

<b><i>Introduction:</i></b> Second primary tumors (SPTs) in head and neck cancer are thought to occur from premalignant lesions that are present at the time of the primary tumor diagnosis. The association of the modality used to treat the primary lesion with SPT occurrence is not clear. <b><i>Objective:</i></b> The aim of the study was to assess the incidence of SPTs in patients with head and neck malignancies, according to treatment modality. <b><i>Methods:</i></b> We conducted a retrospective cohort study. All patients who were treated at Soroka Medical Center between 2000 and 2013 for a head and neck squamous cell carcinoma were assessed. Data analysis included tumor site of the primary and second primary and treatment modality of the primary tumor. In addition, demographics as well as habits were recorded as well. <b><i>Results:</i></b> Of the 184 patients included in the cohort, SPT developed in 31 patients (17%) with a median time to diagnosis of 4.3 years. Smoking was reported in 74% of those with SPT and 78% of those without. The most common site for SPT was the lungs, with 13 cases, 42% of the total SPTs. Among patients who developed an SPT, for 12 of those with an index tumor in the oral cavity or oro-hypopharynx, 8 (67%) developed an SPT in the same location; for 18 of those with an index tumor in the larynx, 11 (61%) developed a SPT in the lungs and bronchi (<i>p</i> = 0.001). On multivariate analysis, the treatment modality used was not found to be associated with the occurrence of SPTs and the radiotherapy showed no protective or harmful effect (HR 0.64 <i>p</i> = 0.24). <b><i>Conclusion:</i></b> Treatment modality used for head and neck cancer does not seem to be associated with the occurrence of SPTs.

Screening for synchronous esophageal second primary tumors in patients with head and neck cancer

Summary Patients with head and neck squamous cell carcinoma (HNSCC) have an increased risk of developing esophageal second primary tumors (ESPTs). We aimed to determine the incidence, stage, and outcome of synchronous ESPTs in patients with HNSCC in a Western population. We performed a prospective, observational, and cohort study. Patients diagnosed with HNSCC in the oropharynx, hypopharynx, any other sub-location in combination with alcohol abuse, or patients with two synchronous HNSCCs, between February 2019 and February 2020 underwent screening esophagogastroduodenoscopy (EGD). ESPT was defined as presence of esophageal squamous cell carcinoma (ESCC) or high grade dysplasia (HGD). Eighty-five patients were included. A lesion suspected for ESPT was detected in 14 of 85 patients, which was pathologically confirmed in five patients (1 ESCC and 4 HGD). The radiotherapy field was extended to the esophagus in two of five patients, HGD was treated with endoscopic resection in three of five patients. None of the ESPTs were detected on MRI and/or CT-scan prior to EGD. Of the remaining nine patients, three had low grade dysplasia on histology whereas the other six patients had benign lesions. Incidence of synchronous ESPT was 5.9% in our cohort of HNSCC patients. All ESPTs were diagnosed at an early stage and treated with curative intent. We recommend that screening for synchronous ESPTs should be considered in a selected group of patients with HNSCC.

Delayed Response After Confirmed Progression (DR) and Other Unique Immunotherapy-Related Treatment Concepts in Cutaneous Squamous Cell Carcinoma

Non-melanoma skin cancers are one of the most common cancers diagnosed worldwide, with the highest incidence in Australia and New Zealand. Systemic treatment of locally advanced and metastatic cutaneous squamous cell carcinomas has been revolutionized by immune checkpoint inhibition with PD-1 blockade. We highlight treatment issues distinct to the management of the disease including expansion of the traditional concept of pseudoprogression and describe delayed responses after immune-specific response criteria confirmed progressive disease with and without clinical deterioration. We term this phenomenon “delayed response after confirmed progression (DR)”. We also discuss the common development of second primary tumors, heterogeneous disease responses, and expanding clinical boundaries for immunotherapy use.

Frequency and Localization of Second Primary Tumors in Patients with Oropharyngeal Carcinoma—The Influence of the Human Papilloma Virus

Purpose: To investigate the frequency, localization, and survival of second primary tumors (SPT) of oropharyngeal squamous cell carcinoma (OPSCC) depending on human papillomavirus (HPV) status. Methods: We performed a retrospective chart analysis of 107 OPSCC patients treated at the Zurich University Hospital from 2001 to 2010. Rate and localization of SPT after an index OPSCC were stratified according to smoking and HPV infection status. Results: In total, 57/91 (63%) included patients showed an HPV-associated OPSCC. Of these, 37/57 (64.9%) patients with an HPV-positive and 32/34 (94.1%) patients with an HPV-negative OPSCC were smokers. The median age at diagnosis of the SPT was 59.54 years (interquartile range 52.7–65.6). In addition, 8/57 (14%) HPV-positive and 13/34 (38.2%) HPV-negative patients developed SPT. The rate of SPT in patients with HPV-positive index tumors was significantly lower than in patients with HPV-negative OPSCC (p-value 0.01). Smokers showed significantly more SPT in the head and neck area than outside. The development of an SPT led to a significantly lower survival time in HPV-negative patients, while it did not significantly affect the survival time of HPV-positive patients. Conclusions: Patients with HPV-positive index tumors had a significantly lower risk of developing SPT than patients with HPV-negative tumors. If SPT developed, survival was significantly shorter in patients with HPV-negative tumors than with HPV-positive tumors.