Metastatic Oropharyngeal Squamous Cell Carcinoma Research Articles

8791 A Case of Hyperfunctioning Thyroid Nodules Evaluated for Thyroid Metastasis in the Setting of Oropharyngeal Squamous Cell Carcinoma

Abstract Disclosure: M. Alashoor: None. J. Gogineni: None. A. Bakar: None. Introduction: Identifying and evaluating hyperfunctioning thyroid nodules in the setting of metastatic head and neck cancers represents a diagnostic challenge that may result in inaccurate identification of perithyroidal lymph node metastasis as malignant or metastatic thyroid nodules with standard workup. Case presentation: A 72-year-old male with a history of stage IV metastatic oropharyngeal squamous cell carcinoma, metastasized to the lymph nodes, lungs, mediastinum, and bilateral iliac bones. He was diagnosed two years ago and received chemotherapy, maintenance immunotherapy with pembrolizumab, and targeted palliative radiation therapy, with good clinical response. Restaging PET-CT two years later revealed local progression. During his workup, he was noted to have persistently abnormal thyroid function test with low TSH (0.03​​µIU/mL, n 0.3-5.33), normal free T4 (0.97ng/dL, n 0.60 - 1.40), mildly elevated free T3 (3.91pg/mL, n 2.5-3.9), negative thyrotropin receptor antibodies levels, negative TSI, negative TPO antibody, noted evidence of subclinical hyperthyroidism consistent over the past year. Radioactive iodine uptake demonstrated multinodular gland, mildly elevated 24-hour uptake of 28% consistent with hyperthyroidism, with decreased activity in the left lobe. Thyroid ultrasound revealed multiple probable malignant thyroid nodules, a 1.8 cm TI-RADS 5 lesion of the deep margin of the lower pole of the right lobe, and a 1.6 cm TI-RADS 5 lesion of the upper pole on the right lobe. He was treated with methimazole 5 mg. Further workup with fine needle aspiration demonstrated the right upper lobe nodule sample was positive for squamous cell carcinoma, findings suspicious for metastasis. He subsequently proceeded with radical tonsillectomy, right neck dissection, and right hemithyroidectomy. Surgical pathology results noted, right neck metastatic HPV-associated squamous cell carcinoma involving the lymph nodes with extranodal extension, right oropharyngeal HPV-mediated squamous cell carcinoma. The thyroid gland biopsy was significant for incidental papillary microcarcinoma 2mm, thyroid follicular nodular disease, without evidence of squamous cell carcinoma or metastatic infiltration. Post-hemithyroidectomy, his thyroid function normalized, and methimazole was discontinued. Conclusion: Thyroid metastasis from head and neck cancers represent a rare entity. In patients with a history of malignancy, evaluation of new thyroid masses remains crucial. While FNA is a sensitive method for detecting thyroid metastases, inaccuracies may occur, impacting the identification of thyroid nodules in the presence of local metastatic lymphadenopathy. Identifying squamous cell carcinoma in the thyroid can significantly influence the treatment plan of patients with metastatic carcinomas, therefore careful consideration must be undertaken on evaluation. Presentation: 6/1/2024

Primary Site Surgery in Distantly Metastatic Oropharyngeal Squamous Cell Carcinoma.

Determine if intensive local therapy (i.e., local surgery or radiation) has a survival benefit for patients presenting with distantly metastatic oropharyngeal squamous cell carcinoma (OPSCC). Retrospective population-based cohort study of patients in the National Cancer Database presenting with distantly metastatic OPSCC. Overall survival (OS) was compared for patients receiving systemic therapy alone or in combination with local surgery or curative dose radiation, controlling for various clinicodemographic factors. Between 2010 and 2015, 627 patients presented with newly diagnosed, metastatic OPSCC and an initial treatment course including systemic chemotherapy. Multivariable analysis demonstrated that local radiation therapy was independently associated with improved OS (OR 0.64, CI [0.51-0.81]); local surgery was not independently associated with improved OS (OR 0.99, CI [0.65-1.53]). Higher T stages were associated with worse OS (OR 1.69, CI [1.14-2.50] for T3 and OR 1.77, CI [1.22-2.58] for T4 compared to T1). HPV-positive (HPV+) tumors were associated with improved OS compared to HPV- (OR 0.79, CI [0.64-0.97]). Multiagent chemotherapy was associated with improved OS compared to single-agent (OR 0.78, CI [0.62-1.00]). The best survival for the entire cohort and for HPV+ patients was for radiation with systemic therapy and the worst survival for systemic therapy alone. Curative dose local radiotherapy in addition to systemic therapy is associated with improved OS compared to systemic therapy alone in patients presenting with distantly metastatic OPSCC. There is not a significant survival benefit for local surgery in addition to systemic therapy in this patient population, regardless of HPV status. 3 Laryngoscope, 134:2243-2251, 2024.

Accuracy and Interobserver Agreement in High-Risk HPV RNA Chromogenic In-situ Hybridization on Cell Blocks from Metastatic Oropharyngeal Squamous Cell Carcinoma

Accuracy and Interobserver Agreement in High-Risk HPV RNA Chromogenic In-situ Hybridization on Cell Blocks from Metastatic Oropharyngeal Squamous Cell Carcinoma

Distinct Outcomes of Oropharyngeal Squamous Cell Carcinoma Patients after Distant Failure According to p16 Status: Implication in Therapeutic Options.

Introduction: Recent modifications in the epidemiology of oropharyngeal squamous cell carcinoma (OSCC) have led to the increase of Human papillomavirus (HPV) related metastatic head and neck cancer patients with high life expectancy even at advanced stage, low comorbidity and still restricted systemic therapy opportunities. In the recent era of ablative therapies’ development, oligometastatic HPV OSCC patients are indubitably good candidates for intensified treatment. However, data related to outcomes after optimised management of metastatic sites are dramatically missing. Materials and patients: In our cohort of 186 unselected consecutive OSCC patients treated with curative intent at our institution between 2009 and 2013, we analysed the incidence, treatment and outcomes of distant metastatic (DM) failure according to p16 status. Results: After a median follow-up of 4.2 years (95% CI: 3.8–4.4) from primary diagnosis of OSCC, 21/95 p16− patients (22.1%) vs. 8/91 (8.8%) p16+ patients presented DM failure with a median interval of 11 (range 0–46) and 28 months (range 0–71), respectively (p = 0.10). Overall survival (OS) after DM failure was significantly higher in p16+ patients with a two-year OS rate of 75% and 15% for p16+ and p16−, respectively (p = 0.002). In eight HPV-related metastatic patients, three underwent ablative lung metastasis treatment and are still complete responders four to five years later. Conclusion: This study highlights distinct outcomes of metastatic HPV-related OSCC patients emphasised by three long-term complete responders after lung ablative treatment. In patients with high life expectancy and limited tumour burden, the question of ablative treatment such as metastasectomy or stereotactic ablative radiotherapy (SBRT) should be addressed.

An Experimental Single-Case Design in Effectiveness of Oxytocin on Reducing Alcohol Addiction in a Patient with Oropharyngeal Carcinoma-the Mediation Role of Difficulties in Emotional Regulation

Oxytocin, due to its potential for modulation of cravings, is a possible alternative therapy for alcohol dependency. Management or cessation of alcohol use can increase the survival rates in cancers affected by alcohol abuse. The present study is an experimental single-case, reversal design study that has a multiple baselines and a 6- month follow-up. The study was conducted between January 2014 and November 2015. The patient was a 67-year-old man, known to abuse alcohol, who had a diagnosis of metastatic oropharyngeal squamous cell carcinoma and dysthymia syndrome. He was selected by a respondent-driven sampling method. The patient was treated with intranasal oxytocin in two stages and for six weeks. In the control phase, he used a placebo. The primary outcomes were the Addiction Severity Index results and changes to the Difficulties in Emotion Regulation Scale. The secondary outcome was the relationship between emotion regulation and addiction severity. The data were analyzed by the generalized estimation equation, linear mixed models (random effect model) with repeated measures, and correlation with repeated measures. Primary outcomes showed that intranasal oxytocin caused a significant decrease in addiction severity in its interaction with regulation of emotion. However, this reduction was not sustained until the follow-up stage. Secondary outcomes showed a direct relationship between the difficulty in controlling emotions and the severity of alcohol addiction. Oxytocin could decrease addiction severity by decreasing cue reactivity; thus, it could be considered an effective intervention in the field of addiction.

Effectiveness of Oxytocin on Reducing Alcohol Consumption and Depression Syndrome in a Patient with Oropharyngeal Carcinoma

Introduction: Stopping or controlling alcohol consumption in alcohol-related cancers can increase survival rates. Oxytocin due to its potential in craving modulation has been suggested as an alternative therapy. Case Presentation: The patient was alcohol-abused 67-year-old male with a diagnosis of metastatic oropharyngeal squamous cell carcinoma and dysthymia syndrome, which was selected using a respondent-driven sampling (RDS) method. The patient was treated with intranasal oxytocin in two stages and for 6 weeks, and in the control phase, placebo was used. Alcohol consumption rate, its related problems, and changes in the depression index were considered as the primary outcome. The association of mood with alcohol consumption was considered as the secondary outcome. The data were analyzed, using the generalized estimation equation (GEE), a generalized linear mixed models (random effect model) with repeated measures, and repeated measures correlation. Primary outcomes showed that intranasal oxytocin caused a significant decrease in alcohol consumption and its problems related to mood. However, this reduction did not remain until the follow-up stage. Secondary outcomes showed that there is a direct relationship between the dysthymia index and alcohol consumption. Conclusions: The reduction of neurotic cue reactivity induced by the oxytocin function can, with the improvement of the mood, stop the cycle of craving and consumption. However, this hypothesis requires controlled clinical trials.

Emerging insights into recurrent and metastatic human papillomavirus-related oropharyngeal squamous cell carcinoma.

ABSTRACTObjectiveTo review recent literature on human papillomavirus‐related (HPV‐positive) oropharyngeal squamous cell carcinoma (OPC) and focus on implications of recurrent and metastatic disease.MethodsPrimary articles from 1990 to 2016 indexed in MEDLINE (1) pertaining to the epidemiology of HPV‐positive OPC and (2) providing clinical insight into recurrent and metastatic OPC.ResultsThe incidence of HPV‐positive OPC is increasing globally. HPV‐positive OPC is a subtype with distinct molecular and clinical features including enhanced treatment response and improved overall survival. While disease recurrence is less common in patients with HPV‐positive OPC, up to 36% of patients experience treatment failure within eight years. Recurrent and metastatic OPC has historically signified poor prognosis, however recent data are challenging this dogma. Here, we discuss recurrent and metastatic OPC in the context of HPV tumor status.ConclusionHPV‐positive OPC exhibits distinct genetic, cellular, epidemiological, and clinical features from HPV‐negative OPC. HPV tumor status is emerging as a marker indicative of improved prognosis after disease progression in both locoregionally recurrent and distant metastatic OPC.Level of EvidenceN/A.

Performance of Aptima E6/E7 mRNA HPV assays on fine needle aspirates from cervical lymph nodes of patients with metastatic oropharyngeal squamous cell carcinoma

Performance of Aptima E6/E7 mRNA HPV assays on fine needle aspirates from cervical lymph nodes of patients with metastatic oropharyngeal squamous cell carcinoma

Surgical salvage improves overall survival for patients with HPV-positive and HPV-negative recurrent locoregional and distant metastatic oropharyngeal cancer.

Human papillomavirus (HPV) tumor status and surgical salvage are associated with improved prognosis for patients with recurrent oropharyngeal squamous cell carcinoma (OPSCC). Current data regarding types of surgery and the impact of surgery for patients with distant metastatic disease are limited. A retrospective analysis of patients with recurrent OPSCC from 2 institutions between 2000 and 2012 was performed. p16 immunohistochemistry and/or in situ hybridization, as clinically available, were used to determine HPV tumor status. Clinical characteristics, distribution of recurrence site, and treatment modalities were compared by HPV tumor status. Overall survival (OS) was examined using Kaplan-Meier and Cox proportional hazards methods. The current study included 108 patients with 65 locoregional and 43 distant metastatic first recurrences. The majority of patients were HPV-positive (80 patients). HPV-positive tumor status was associated with longer time to disease recurrence (P<.01). Anatomic site distribution of disease recurrences did not differ by HPV tumor status. HPV-positive tumor status (adjusted HR [aHR], 0.23; 95% confidence interval [95% CI], 0.09-0.58 [P = .002]), longer time to disease recurrence (≥ 1 year; aHR, 0.36; 95% CI, 0.18-0.74 [P = .006]), and surgical salvage (aHR, 0.26; 95% CI, 0.12-0.61 [P = .002]) were found to be independently associated with OS after disease recurrence. Surgical salvage was independently associated with improved OS compared with nonsurgical treatment among patients with both locoregional (aHR, 0.15; 95% CI, 0.04-0.56 [P = .005]) and distant (aHR, 0.19; 95% CI, 0.05-0.75 [P = .018]) metastatic disease recurrences. Surgical salvage was found to be associated with improved OS for patients with recurrent locoregional and distant metastatic OPSCC, independent of HPV tumor status. Further prospective data are needed to confirm the role of surgical salvage for distant metastases.

ALDH1-positive cancer stem-like cells are enriched in nodal metastases of oropharyngeal squamous cell carcinoma independent of HPV status

Oropharyngeal squamous cell carcinoma (OSCC) is caused by high-risk (HR) human papillomavirus (HPV) or alcohol and tobacco abuse. Aldehyde dehydrogenase 1 (ALDH1) is a confirmed marker for cancer stem-like cells (CSCs) of OSCC responsible for therapy resistance, recurrence and metastasis. Associations between HR-HPV/p16, CSC frequency and clinicopathological parameters in patients with metastatic OSCC were investigated. In the present study, HPV genotypes and expression of ALDH1 and p16 was analyzed in 40 paired OSCC and metastases. A significant correlation between ALDH1 positivity with lower primary tumor differentiation grade (P=0.009) and higher nodal status (P=0.015) was noted. Compared to primary tumors, the proportion of ALDH1-expressing cells was significantly increased in metastases (P=0.012), while significantly fewer ALDH1-expressing cells were found in HR-HPV-DNA⁺/p16⁺ primary tumors (P=0.038) compared to HR-HPV-DNA⁻/p16⁻ primary tumors. Metastases showed no difference. ALDH1⁺ CSCs are detectable in OSCC and metastases. ALDH1 high-grade OSCC exhibits a more aggressive phenotype characterized by higher nodal classification and lower differentiation. This suggests a subpopulation contained in the ALDH1-positive OSCC cell pool able to complete the metastatic cascade and subsequently enriching in metastasis independent of tumor etiology and ALDH1 content.

Oncological safety of the Hayes-Martin manoeuvre in neck dissections for node-positive oropharyngeal squamous cell carcinoma

The Hayes-Martin manoeuvre involves ligation of the posterior facial vein and superior reflection of the investing fascia below the mandible to preserve the marginal mandibular nerve. The peri-facial nodes thus remain undissected. We perform this manoeuvre routinely during modified radical neck dissection for metastatic oropharyngeal squamous cell cancer. Here, we review the oncological safety and marginal mandibular nerve preservation rates of this manoeuvre from 2004 to 2009. Retrospective review of the head and neck oncology database (2004-2009) at Addenbrooke's Hospital, Cambridge, UK, a tertiary referral centre for head and neck oncology. Thirty-four patients underwent modified radical neck dissection for metastatic oropharyngeal squamous cell carcinoma. The primary tumour included the tonsil in 19 cases, base of tongue in 10 and posterior pharyngeal wall in 5. The neck nodal status was N1 in 4 cases, N(2a) in 11, N(2b) in 10, N(2c) in 4 and N(3) in 5. All patients had adjuvant radiotherapy. Median follow up was four years (range, two to five). No peri-facial nodal region recurrences were seen. Four patients had temporary marginal mandibular nerve weakness; beyond two months, no weakness was seen. In neck dissections for oropharyngeal squamous cell carcinoma, the marginal mandibular nerve and accompanying facial nodes can be safely preserved without oncological risk using the Hayes-Martin manoeuvre.