Oral Oncology 2021-09-08

Effect of elective neck dissection versus sentinel lymph node biopsy on shoulder morbidity and health-related quality of life in patients with oral cavity cancer: A longitudinal comparative cohort study

Gerben van Hinte, Tolunay Sancak, Willem L.J. Weijs, Matthias A.W. Merkx, Ruud A. Leijendekkers, Maria W.G. Nijhuis-van der Sanden, Robert Takes, Caroline M. Speksnijder

Publication date 08-09-2021


To research the difference in shoulder morbidity and health-related quality of life between patients with cT A longitudinal study with measurements before surgery, 6 weeks, 6 months, and 12 months after surgery. Shoulder morbidity were determined with measurements of active range of motion of the shoulder and patient-reported outcomes for shoulder morbidity (SDQ, SPADI) and health-related quality of life (HR-QoL) (EQ5D, EORTC-QLQ-HN35). Linear mixed model analyses were used to analyze differences over time between patients that had END, SLNB or SLNB followed by complementing neck dissection. We included 69 patients. Thirty-three patients were treated with END. Twenty-seven patients had SLNB without complementing neck dissection (SLNB), and nine were diagnosed lymph node positive followed by completion neck dissection (SLNB + ND). Ipsilateral shoulder abduction (P = .031) and forward flexion (P = .039) were significantly better for the SLNB group at 6 weeks post-intervention compared to the END and SLNB + ND group. No significant differences for shoulder morbidity, or health-related quality of life were found at 6 weeks, 6 months, and 12 months between the three groups. With oncologic equivalence for the END and SLNB as strategies for the cN

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Is cellularity alone sufficient to sub-grade malignant melanoma histologically as spindle cell/desmoplastic variant?

Deepak Pandiar, Pratibha Ramani, Reshma Poothakulath Krishnan, Casilda L. Sushanthi, Abilasha Ramasubramanian

Publication date 22-08-2021


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The characteristics and prospects of reflectance confocal microscopy for noninvasive diagnosis of oral potentially malignant disorders

Wei Liu, Xi Yang, Zhengyu Shen, Linjun Shi

Publication date 16-08-2021


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Definitive tumor directed therapy confers a survival advantage for metachronous oligometastatic HPV-associated oropharyngeal cancer following trans-oral robotic surgery

Christopher M. Wright, Daniel Y. Lee, David Shimunov, Ruben Carmona, Andrew R. Barsky, Lova Sun, Roger B. Cohen, Joshua M. Bauml, Robert M. Brody, Devraj Basu, Christopher H. Rassekh, Ara A. Chalian, Jason G. Newman, Karthik Rajasekaran, Gregory S. Weinstein, John N. Lukens, Alexander Lin, Samuel Swisher-McClure

Publication date 03-09-2021


To assess the prognostic significance of oligometastatic versus polymetastatic disease in human papillomavirus (HPV)-associated oropharyngeal squamous cell carcinoma (OPSCC), and to evaluate the impact of definitive tumor directed therapy on the survival outcomes for patients with oligometastatic disease when compared to systemic therapy. This was a retrospective observational cohort study of patients with HPV-associated OPSCC who developed distant metachronous metastatic disease after undergoing initial primary surgical management from 2008 to 2017. We classified patients based on the extent of metastatic disease [Oligometastatic (≤5 metastases) and polymetastatic (>5 metastases)], and the initial treatment of metastatic disease [definitive tumor directed therapy (all metastases treated with surgery or radiotherapy) versus upfront systemic therapy]. Among 676 patients undergoing primary surgical management for HPV-associated OPSCC, 39 patients (5.8%) developed metastases after a median follow-up of 29.6 months (range 4.5-127.0). Of the 34 metastatic patients who met study criteria, 26 (76.5%) were oligometastatic and 8 (23.5%) were polymetastatic. Oligometastatic patients had improved median overall survival (OS) compared to polymetastatic patients (47.9 vs. 22.7 months, p = 0.036). For oligometastatic patients, definitive tumor directed therapy was associated with an improved median progression free survival (not reached vs 6.13 months, p = 0.001) and median OS (not reached vs 40.7 months, p = 0.004). In a cohort of patients surgically treated for HPV-associated OPSCC, metachronous metastatic disease was uncommon and, in most cases, considered oligometastatic. Oligometastasis portends a favorable prognosis and definitive tumor directed therapy may be associated with improved overall survival in these patients. Future multi-institutional efforts are warranted to further demonstrate the impact of definitive tumor directed therapy on disease outcomes.

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Associations between testosterone and patient reported sexual outcomes among male and female head and neck cancer patients before and six months after treatment: A pilot study

Irma M. Verdonck-de Leeuw, Heleen Melissant, Birgit I. Lissenberg-Witte, Robert J. Baatenburg de Jong, Martin den Heijer, Johannes A. Langendijk, C. René Leemans, Johannes H. Smit, Robert P. Takes, Chris H.J. Terhaard, Femke Jansen, Ellen Laan

Publication date 31-08-2021


To investigate associations between testosterone and patient reported sexual problems and need for sexual care in head and neck cancer patients at time of diagnosis and 6 months after treatment. Data and samples were used of 40 patients (20 men, 20 women) before and 6 months after treatment. Outcome measures were total testosterone level (TT) and free testosterone index (FTI), testosterone insufficiency (TI), the EORTC QLQ-HN35 Sexuality subscale, the subscales of the International Index of Erectile Function (IIEF), Female Sexual Function Index (FSFI), and the Sexuality subscale of the Short-Form Supportive Care Needs Survey (SCNS-SF34). In men, higher FTI before treatment was significantly associated with better IIEF Orgasm (p = 0.020) and at 6 months follow-up with IIEF Desire (p = 0.019). Before treatment, insufficient testosterone was present in 5 males (25%) and in 3 at follow-up (15%) (2 patients who had TI before treatment plus one). In women, higher TT at follow-up was significantly associated with better EORTC Sexuality (p = 0.031) and FSFI Satisfaction (p = 0.020); FTI at follow-up was associated with FSFI Satisfaction (p = 0.012). Before treatment, TI was present in 2 women (10%) and in 3 (15%) at follow-up (the same 2 patients plus one). This pilot study showed that testosterone seems to be associated with patient reported sexual outcomes among male and female head and neck cancer patients. It is estimated that 10-25% of HNC patients may have testosterone insufficiency before treatment and/or at 6 months after treatment.

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Surgical and oncological outcomes of transoral robotic total laryngectomy: A case series

Stéphane Hans, Emilien Chebib, Younès Chekkoury-Idrissi, Léa Distinguin, Marta Circiu, Grégoire Vialatte de Pemille, Aude Julien-Laferriere, Lise Crevier-Buchman, Jérôme R. Lechien

Publication date 03-09-2021


To evaluate the oncological, functional and voice rehabilitation outcomes of transoral robotic surgery for total laryngectomy (TORS-TL). A retrospective chart review of patients treated by TORS-TL was conducted at a single academic medical center.
The following outcomes were studied: indication; average robotic set-up and operative times; mean estimated blood loss; postoperative complications; re-feeding features; mean hospital stay; need of adjuvant therapy and voice rehabilitation type. TORS-TL was performed in 10 patients for the following indications: nonfunctional larynx (N = 2); low-grade cricoid chondrosarcoma (N = 3) and recurrent laryngeal cancer after (chemo) radiation (N = 5). Two patients were excluded because the larynx was not exposable. Average robotic set-up and operative times were 20 and 278 min, respectively. The mean estimated blood loss was 50 mL. The mean hospital stay was 13.9 days (8-28 days). There was no local recurrence in patients operated for cancer recurrence (N = 5) 5 years after the surgery. Distant metastases occurred in one patient. A patient with laryngeal chondrosarcoma experienced local failure 3 years after TORS-TL. The voice rehabilitation consisted of esophageal voice (N = 2) and tracheoesophageal prosthesis (Provox®, N = 8). The main reasons for prosthesis replacement were transprosthetic (79%) and periprosthetic leaks (21%). The median lifespan of prostheses was 81 days. TORS-TL may be a safe and effective surgical approach for selected surgical indications. Future controlled studies are needed to determine additional indications and limitations of this procedure.

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Development and validation of a population-based model for predicting the regional lymph node metastasis in adolescent differentiated thyroid carcinoma

Yu Min, Ke Xiang, Yang Feng, Hang Chen, Jialin Chen, Xiaoyuan Wei, Guobing Yin

Publication date 28-08-2021


Adolescent differentiated thyroid carcinoma (DTC) is a rare type of thyroid cancer that represents a special entity of all endocrine-related cancer. This study aims to establish the first nomogram for predicting the regional (central and lateral) lymph node metastasis (LNM) in the adolescent population for better surgical management. We retrospectively reviewed the clinicopathology characteristics of adolescent patients with DTC in the Surveillance, Epidemiology, and End Results database between 2010 and 2015. A total of 1,930 adolescent patients between the ages of 10 and 24 years from the SEER database were enrolled in this study. Six predictive factors including age, race, histology, multifocality, extrathyroidal invasion (EI) and tumor size were identified to be significantly associated with the regional LNM via univariate and multivariate logistic regression analyses. These indicators were used to construct a nomogram for predicting the regional LNM in adolescent patients with DTC. Moreover, a satisfied predictive ability of the model was determined with a C-index of 0.794, supported by an internal validation group with a C-index of 0.776. The Decision Curve Analysis and calibration curve further conducted a great agreement in our model. The first predictive model containing multiple factors has been successfully established with good discrimination for predicting the regional LNM in adolescent patients with DTC. This nomogram could effectively help surgeons to make better individualized surgical decision intraoperatively, especially in terms of whether cervical lymph node dissection (LND) is warranted.

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Delayed diagnosis of palatal adenoid cystic carcinoma: Review of diagnostic workup and image features of perineural spread

Peggy P. Lee, Griffin C. Guess, Austin E. Schumacher, Roberta W. Dalley

Publication date 27-08-2021


Adenoid cystic carcinoma (ACC) is the malignancy most likely to spread perineurally. Delayed diagnosis often leads to undetected perineural spread (PNS). Better understanding of diagnostic processes, clinical and imaging features in ACC may allow earlier diagnoses. A retrospective records search of the University of Washington Radiology archive identified patients with palatal ACC diagnosis and pre-treatment MDCT and/or MRI. Demographic data, clinical findings, diagnostic workup history and image features including the presence of PNS were recorded. 44 patients met inclusion and exclusion criteria. Symptoms included pain, mass, numbness, and sinonasal congestion. The most common finding on clinical examination was visible or palpable palatal mass. 55% of patients were evaluated by a dentist pre-diagnosis. Most common initial impressions were infection and/or dental disease. PNS was identified in 81.8% of patients, most commonly at pterygopalatine fossa, palatine foramina/canals, Vidian canal, or foramen rotundum. PNS was statistically significantly associated with paresthesia (p = 0.003) but not with tumor size, age, gender, or tobacco history. 44% of patients were diagnosed ≥1 year from initial symptoms, with a mean delay of 18.3 (range < 1-72) months. This study represents the first analysis of the nature of the diagnostic process of palatal ACC. Majorities of patients were evaluated by a general dentist pre-diagnosis. PNS was identified in a majority of patients and all the patients who presented with paresthesia had evidence of PNS. Despite patients presenting with paresthesia, palatal ACC is often initially misdiagnosed resulting in delayed diagnosis.

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Identification of patients for a delayed extubation strategy versus elective tracheostomy for postoperative airway management in major oral cancer surgery: A prospective observational study in seven hundred and twenty patients

Sheila Nainan Myatra, Sushan Gupta, Anil K. DCruz, Vithal Rajanala, Harsh Dhar, Shilpi Sharma, Jigeeshu Vasishtha Divatia

Publication date 28-08-2021


Tracheostomy (TT) and delayed extubation (DE) are two approaches to postoperative airway management in patients after major oral cancer surgery. We planned a study to determine the safety of overnight intubation followed by extubation the next morning (DE) compared to elective TT and to identify factors that were associated with a safe DE (maintenance of a patent airway). We conducted a prospective observational study in a tertiary referral cancer care center. We included adult patients undergoing elective major oral cancer surgery under general anesthesia with tracheal intubation. The decision regarding postoperative airway management using either TT or DE was made according to the usual practice at our center. We screened a total of 4477 patients, 720 patients were included. DE was performed in 417 patients (58.4%) and TT in 303 patients (42.4%). On multivariable analysis, T1-T2 tumor stage, absence of extensive resection, primary closure or reconstruction using fasciocutaneous flap, absence of preoperative radiation, no neck dissection or unilateral neck dissection and shorter duration of anesthesia were independent predictors for a safe DE. Overall complications (4.3% versus 22.5%, p = 0.00) and airway complications (1.7% versus 8.7%, p = 0.00) were lower in the DE compared to the TT group respectively. DE was associated with a shorter hospital stay (7.2 ± 3.7 versus 11.5 ± 7.2 days, p = 0.00), time to oral intake and speech compared to TT. A DE strategy after major oral cancer surgery is a safe alternative to TT in a select group of patients.

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Right colonic interposition for severe pharyngoesophageal stricture in head and neck patients: A feasible rescue strategy after multiple failed reconstructive options

C Carnevale, A Pagán-Pomar, A Bianchi, P Sarría-Echegaray, C Morales-Olavarría, G Til-Pérez

Publication date 06-09-2021


Severe pharyngeal stricture is an uncommon complication that may occur afer laryngectomy especially in irradiated patients. Its management is a challenge and high risk of recurrence after reconstruction exists. We present two patients with severe end-stage pharyngoesophageal stricture after several failed attempts of reconstruction with regional and free flaps, in which a right colon transposition was performed. Twenty days after surgery both patients were able to tolerate an oral diet, and no minor or major complications were observed. Right colonic transposition may be a valid option for secondary pharyngeal reconstruction if other less invasive methods such as regional or free flaps have failed to restore the pharyngoesophageal continuity or if the inferior location of stricture makes a tension free anastomosis impossible.

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The impact of induction chemotherapy on long-term quality of life in patients with locoregionally advanced nasopharyngeal carcinoma: Outcomes from a randomised phase 3 trial

Qi Yang, Le Xia, Mei Lin, Meng-Xia Zhang, Chong-Yang Duan, You-Ping Liu, Yu-Long Xie, Zhi-Qiang Wang, Rui You, Xiong Zou, Yi-Jun Hua, Pei-Yu Huang, Rui Sun, Ming-Huang Hong, Ming-Yuan Chen

Publication date 24-08-2021


Our previous trial confirmed that induction chemotherapy (IC) improved long-term survival outcomes in patients with locoregionally advanced nasopharyngeal carcinoma (NPC). In this study, we investigated the impact of IC on long-term quality of life (QoL) in this cohort. Our trial was a randomised, open-label phase 3 trial comparing IC followed by concurrent chemoradiotherapy (CCRT) versus CCRT alone in patients with stage III-IVB (except T3N0-1) NPC. All participants completed two self-administered questionnaires, the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire C30 (QLQ-C30) and the EORTC QLQ Head and Neck Cancer-Specific Module (H&N35). As per protocol, the questionnaires had to be completed before knowledge of treatment allocation by the patient (baseline). Patients were then approached to enroll at the time of the present study period. Ultimately, QoL data from 228 patients were included in the analysis. Most scales were both statistically and clinically decreased in both groups between baseline and the latest follow-up. The IC followed by CCRT group had significantly better outcome in role functioning, cognitive functioning, social functioning, fatigue, pain, and constipation in QLQ-C30 scales at the last follow-up. Similarly, in H&N35 scales, a significantly better result was observed in pain, sexuality, sticky saliva, pain killers use, nutritional supplements, and weight loss, but a poorer result in senses problems, for those treated by IC followed by CCRT. IC followed by CCRT seemed to have better long-term QoL outcomes compared with CCRT alone in patients with locoregionally advanced NPC.

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Survival analysis of patients with advanced hypopharyngeal cancer comparing patients who received primary surgery to those who received chemoradiation: An analysis of the NCDB

Colleen G. Hochfelder, Vikas Mehta, Rafi Kabarriti, Aileen P. McGinn, Enrico Castellucci, Thomas J. Ow

Publication date 22-08-2021


The objective of this study was to use the American College of Surgeons' National Cancer Database (NCDB) to examine the association between primary treatment and overall survival (OS) among patients with locoregionally advanced hypopharyngeal cancer. 6,055 adult patients diagnosed between 2004 and 2015 with stage III or IV, M0, hypopharyngeal squamous cell carcinoma were identified within the NCDB. Patients who received primary chemoradiation (CRT) were compared to those that received surgery with adjuvant radiation or chemoradiation (S + Adj). OS was compared between treatment groups using Kaplan-Meier analyses, propensity score adjustment, and Cox regression analyses. The median survival was 22.7 months (IQR 11.0-49.0). The S + Adj group had a significantly higher comorbidity score, higher grade disease, and more advanced stage disease than the CRT group. S + Adj was associated with significantly improved survival when compared to CRT (p < 0.0001). A propensity score adjusting for facility type, facility location, care at multiple facilities, histology, and T stage was developed. S + Adj was associated with longer survival (HR: 0.72, 95% CI: 0.64-0.80) when compared to CRT in a multivariable Cox regression analysis (adjusting for age, race and ethnicity, insurance status, a comorbidity index, diagnosis year, treatment delay, N stage, and the propensity score). S + Adj was associated with significantly improved survival among those with T2 disease (p = 0.02), T3 disease (p = 0.02), and T4 disease (p < 0.0001) in sensitivity analyses examining these subcohorts independently. Among patients with advanced hypopharyngeal cancer reported in NCDB, treatment with S + Adj was associated with longer survival compared to those treated with primary CRT.

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Impact of sarcopenia in locally advanced head and neck cancer treated with chemoradiation: An Indian tertiary care hospital experience

Puneet Nagpal, Deep S. Pruthi, Manish Pandey, Ashu Yadav, Harpreet Singh

Publication date 18-08-2021


Sarcopenia is emerging as a poor prognostic factor in terms of treatment outcome as well as complications in cancer patients. This study aims to determine the prevalence of sarcopenia and its impact on outcome and toxicity in head and neck squamous cell carcinoma (HNSCC) patients treated with definitive chemo radiotherapy. Three hundred patients of locally advanced HNSCC were included. All patients were treated with radical radiotherapy dose of 70 Gy/35# over 7 weeks along with concurrent chemotherapy. Sarcopenia was assessed from radiation planning computed tomography (CT) scans using skeletal muscle mass at level C3. The impact of sarcopenia on treatment outcome, Disease Free Survival (DFS) and toxicity was evaluated. Association between patient factors and outcome was calculated in univariate and multivariate analyses. Sarcopenic patients were more likely to be elderly, female gender and hypopharyngeal primary. The average SMI of the entire patient cohort was 31.9 cm Sarcopenia in HNSCC patients receiving definitive chemo radiotherapy is an independent prognostic factor and is associated with a worse treatment outcome and more toxicities.

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Prognostic impact and potential predictive role of baseline circulating tumor cells in locally advanced head and neck squamous cell carcinoma

Thiago Bueno de Oliveira, Alexcia Camila Braun, Ulisses Ribaldo Nicolau, Emne Ali Abdallah, Vanessa da Silva Alves, Victor Hugo Fonseca de Jesus, Vinicius Fernando Calsavara, Luiz Paulo Kowaslki, Ludmilla T. Domingos Chinen

Publication date 18-08-2021


The prognostic impact of circulating tumor cells (CTCs) or circulating tumor microemboli (CTM) in locally advanced head and neck squamous cell carcinoma (LA-HNSCC) is yet to be determined, with conflicting results in previous trials. The role of induction chemotherapy (ICT) in the management of LA-HNSCC is controversial with no predictive biomarkers to guide treatment strategy in this scenario. The aim of this trial is to determine the prognostic impact of CTCs and CTM, their biomarkers expression by immunocytochemistry (ICC), and its potential role as predictors of ICT benefit in LA-HNSCC. Prospective study, with newly diagnosed stage III/IV non-metastatic LA-HNSCC patients treated with curative intent. Blood samples analyzed for CTCs and CTM before treatment using the ISET method. A total of 83 patients were included. CTCs counts were an independent prognostic factor for overall survival (OS; HR: 1.17; 95 %CI: 1.05-1.31; p = 0.005) and progression free survival (PFS; HR:1.14; 95 %CI: 1.03-1.26; p = 0.007). Using the Lausen and Schumacher technique, 2.8 CTCs/mL for OS and 3.8 CTCs/mL for PFS were defined as the best cut-offs. CTM were detected in 27.7% of patients, correlating with worse PFS (HR = 2.70; IC95%: 1.30-5.58; p = 0.007). MRP-7 expression in CTM correlated with worse OS (HR = 3.49; 95 %CI: 1.01-12.04; p = 0.047) and PFS (HR = 3.62; 95 %CI: 1.08-12.13; p = 0.037). CTCs counts were predictive of complete response to treatment (OR = 0.74; 95 %CI: 0.58-0.95; p = 0.022) and high counts (cut-off 3.8/mL) and CTM were potential predictors of ICT benefit. CTCs/CTM had significant prognostic impact and potential role as predictors of ICT benefit in LA-HNSCC.

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Accuracy of autofluorescence and chemiluminescence in the diagnosis of oral Dysplasia and Carcinoma: A systematic review and Meta-analysis

Antonio Moffa, Lucrezia Giorgi, Andrea Costantino, Luigi De Benedetto, Michele Cassano, Giuseppe Spriano, Giuseppe Mercante, Armando De Virgilio, Manuele Casale

Publication date 17-08-2021


To define the accuracy of autofluorescence-based (AF) and chemiluminescence-based (CL) systems in the diagnosis of oral dysplastic and malignant lesions in addition to the Conventional Oral Examination (COE). The study was performed according to the PRISMA-DTA guidelines. A total of 2631 oral cavity lesions (AF, n = 2076; CL, n = 555) from 26 studies (AF = 17; CL = 9) was used for calculation of diagnostic accuracy parameters. The overall pooled sensitivity and specificity of the AF were 81.3% (95% CI: 74.3% - 87.5%) and 52.1% (95% CI: 36.9% - 67.1%), respectively. Cumulative diagnostic odds ratio (DOR) was 5.44 (95% CI: 2.29 - 10.56) with a significant heterogeneity between studies (I AF and CL present a high sensitivity in the diagnosis of dysplastic and malignant oral cavity lesions, demonstrating that diagnostic biopsies may be avoided in case of a negative test result. Both tests have a low specificity, and the reduction of the false positive rate compared to the COE alone remains poor.

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Regular clinical follow-up of oral potentially malignant disorders results in improved survival for patients who develop oral cancer

Fredrik Jäwert, Jennie Nyman, Emma Olsson, Claudia Adok, Madeleine Helmersson, Jenny Öhman

Publication date 10-08-2021


To evaluate whether clinical follow-up programs of oral potentially malignant disorders (OPMD) result in earlier detection and improved survival rates if malignant transformation occurs, as compared to OPMD patients without follow-up and other patients with oral squamous cell carcinoma (OSCC). Three OSCC groups were retrospectively studied for disease stage at diagnosis and survival rates (N = 739): Group A, patients with OSCC with regular follow-up of preceding OPMD (N = 94); Group B, patients with OSCC with preceding OPMD but no follow-up (N = 68); Group C, patients with OSCC without previously known OPMD diagnosis (N = 577). The patients with OPMD with follow-up (Group A) was diagnosed at a significantly earlier stage and have significantly higher survival rates compared to Group B (p < 0.001 and p = 0.022, respectively) and Group C (p < 0.001 and p < 0.001, respectively). There was no significant difference between Group B and Group C in terms of survival rate (p = 0.143) or stage at diagnosis (p = 0.475). Patients with OPMD and follow-up (Group A) had a 5-year net survival rate of 90.0% (95%CI 80.3-100.8%), as compared to 68.3% percent (95% CI 54.5-85.7) for Group B and 56.1% (95% CI 51.4-61.3) for Group C. The results of this study indicate that regular follow-up of patients with OPMD results in earlier detection of OSCC (if malignant transformation occurs) and improved survival.

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Genomic landscape and tumor mutation burden analysis of Chinese patients with sarcomatoid carcinoma of the head and neck

Hai-bing Chen, Xiao-yang Gong, Wang Li, Dong-sheng Chen, Le-le Zhao, Si Li, Ming-zhe Xiao, Lei Cheng, Xi Chen

Publication date 10-08-2021


Sarcomatoid carcinoma (SC) of the head and neck (HN) is a rare disease that has both sarcomatoid and cancerous components. The genetic background and mechanisms of tumorigenesis remain largely unrevealed, and the progress of precision therapy has been limited. Targeted DNA-based next-generation sequencing (NGS) was performed by a 539 genes panel of pan-cancer in 12 patients with SC of the HN to identify their genetic alterations and investigate clinically actionable mutations for use in precision treatment. TP53 was identified as the most frequently mutated gene. Genes related to the cell cycling, chromatin remodeling and histone modification were found to be frequently mutated in patients with SC of the HN. Alterations in receptor tyrosine kinases (RTKs) were also found in six patients. In addition, four patients had mutations in members of the downstream RAS and PI3-kinase pathways, PIK3CA was identified as the most frequently mutated gene in this pathway. The tumor mutation burden (TMB) value ranged from 0.71 to 14.71 per megabase, with a median of 4.34. The TMB value of PIK3CA mutation patients was significantly higher than that of PIK3CA wild-type patients. This was the first study to investigate genomic alterations specifically in Chinese patients with SC of the HN. Our research results showed that 10 out of 12 patients can match the targeted therapies or immunotherapy currently available in clinical practice or active clinical trials, suggesting precision therapy has the potential utility to improve the long-term prognosis for patients with the rare disease. Due to the small number of patients in this study, the findings need to be validated in a larger cohort.

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Serum selenium predicts achievement of full-dose cisplatin in concurrent chemoradiotherapy for locally advanced head and neck squamous cell carcinoma: A prospective, observational study

Akira Ohkoshi, Ryo Ishii, Shun Wakamori, Yuki Nakayama, Takuya Yoshida, Kenjiro Higashi, Ayako Nakanome, Takenori Ogawa, Yukio Katori

Publication date 08-08-2021


Concurrent chemoradiotherapy (CCRT) with three-weekly high-dose cisplatin (100 mg/m A prospective, observational study was conducted involving 60 patients who received CCRT with three-weekly high-dose cisplatin (100 mg/m Twenty-seven patients achieved full-dose cisplatin (300 mg/m As well as renal function, selenium deficiency is a potential therapeutic target for CCRT with high-dose cisplatin in HNSCC patients.

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TIGIT/CD155 blockade enhances anti-PD-L1 therapy in head and neck squamous cell carcinoma by targeting myeloid-derived suppressor cells

Liang Mao, Yao Xiao, Qi-Chao Yang, Shao-Chen Yang, Lei-Lei Yang, Zhi-Jun Sun

Publication date 02-08-2021


Anti-PD-1/PD-L1 therapy has recently been approved for head and neck squamous cell carcinoma (HNSCC). However, given that large numbers of patients with HNSCC do not respond to PD-1/PD-L1 antibodies, combination strategies for elevating the response rate need to be further investigated. The goal of this study was to explore the possibility of dual-targeting CD155/TIGIT and PD-1/PD-L1 signalling in HNSCC. Multiplex flow cytometry was performed to determine the co-expression of CD155 and PD-L1 in human HNSCC and transgenic HNSCC mouse models. The combined application of TIGIT m Ab and PD-L1 m Ab in a mouse model was used to explore the therapeutic effect. CD155 and PD-L1 were highly co-expressed on myeloid-derived suppressor cells (MDSCs) derived from patients with HNSCC and were inversely associated with the percentage of tumour CD3 Our study indicated that CD155

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Sensory recovery and oral health-related quality of life following tongue reconstruction using non-innervated radial forearm free flaps

Ling Zhu, Jinglu Zhang, Wenjing Chen, Peter Svensson, Kelun Wang

Publication date 06-08-2021


This study aimed to monitor the recovery of somatosensory function and oral health-related quality of life after tongue reconstruction using a non-innervated radial forearm free flap (RFFF). Twenty patients (9 men, age: 42-67 years) underwent tongue reconstruction with non-innervated RFFFs, and twenty age- and sex-matched controls were included in this study. Quantitative sensory testing (QST), including cold, warm, and mechanical detection thresholds (CDT, WDT, MDT); cold, heat, and mechanical pain thresholds (CPT, HPT, MPT); and static two-point, sharp/blunt, and direction discrimination (S2-PD, S/BD, DD) were determined 9 months and 18 months after surgery on the surgical (9 M, 18 M) and contralateral sides (9Mc, 18Mc). Oral Health Impact Profile-49 (OHIP-49) was used to determine the oral-related quality of life of participants. All parameters showed significantly lower sensitivity at 9 M and 18 M (p < 0.001) compared to those for the controls and the contralateral side, except for DD (p = 0.101). In addition, the parameters showed a significant decrease in sensitivity for 9Mc and 18Mc (p ≤ 0.043) compared to those for the controls, except for MPT, HPT, S/SD, and DD (p ≥ 0.453). Findings on WDT, MPT, S2-PD, and DD (p ≤ 0.046) indicated significantly higher somatosensory function at 18 M than that at 9 M. MDT and MPT (p ≤ 0.038) showed significantly higher sensitivity at 18Mc than at 9Mc. Scores for all dimensions of OHIP-49 were significantly higher in patients (decrease in quality of life, p ≤ 0.002) than in controls, except for physical discomfort (p = 0.51). However, the scores were significantly higher at 18 M than at 9 M (p ≤ 0.011), except for handicap (p = 0.36). Postoperative chemotherapy was significantly correlated with impaired thermal sensitivity of the flaps (WDT, p = 0.049). The present findings showed significant impairment in somatosensory function on both the surgical and contralateral sides of patients with RFFFs. However, a significant increase in somatosensory function was observed on both sides over time. Somatosensory disturbances observed after surgery were associated with poor oral health-related quality of life.

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Postoperative oral dysfunction following oral cancer resection and reconstruction: A preliminary cross-sectional study

Yuhei Matsuda, Tatsuo Okui, Masaaki Karino, Noriaki Aoi, Satoe Okuma, Kenji Hayashida, Tatsunori Sakamoto, Takahiro Kanno

Publication date 28-07-2021


Oral cancer treatment reportedly causes decreased oral function, but few studies have examined the effects of oral cancer treatment on oral function in depth. This study aimed to comprehensively evaluate the oral function after treatment and classify the conditions related to oral dysfunction in patients with oral cancer. We recruited participants, collected their background data, and evaluated their oral function from September 2019 to March 2021. Principal component analysis was used to identify the components of oral function measurement and oral health perception. Receiver operating characteristic analysis was performed to investigate the accuracy of oral function measurements in predicting oral intake and nutritional status. Fifty patients treated for oral cancer, including 33 (66.0%) males and 17 (34.0%) females, were included. Their median age was 71.0 years (interquartile range: 63.0-76.0). There were significant differences in oral dryness between males and females, occlusal force among different age groups, tongue pressure based on the tumor stage and performance of reconstructive procedures, and masticatory function and Eating Assessment Tool scores based on whether radiotherapy was performed (P < 0.05). The principal component analysis proposed that oral function measurements and subjective oral health perception could be divided into three main components (transport, oral hygiene, and occlusion type), which explain 61.5% of the variance of the phenomenon. A significant decrease in oral function after oral cancer treatment should be diagnosed as postoperative oral dysfunction. Postoperative oral dysfunction can be classified into three types, each of which may present with different pathologies.

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Robotic surgery may improve overall survival for T1 and T2 tumors of the hypopharynx: An NCDB cohort study

Andrey Finegersh, Rohith S. Voora, Bharat Panuganti, Farhoud Faraji, Floyd Christopher Holsinger, Kevin T. Brumund, Charles Coffey, Joseph Califano, Ryan K. Orosco

Publication date 31-07-2021


Hypopharyngeal cancer is associated with poor survival. Robotic surgery is emerging as a treatment for hypopharyngeal tumors, but no rigorous data are available to assess its effect on survival. The National Cancer Database (NCDB) was used to identify patients with T1 and T2 hypopharyngeal tumors undergoing robotic surgery, laser surgery, and primary radiation with or without chemotherapy from 2010 to 2016. All adult patients with available staging and no distant metastasis were included. We compared 57 patients undergoing robotic surgery, 236 undergoing laser surgery, and 5,742 undergoing primary radiation. Compared to laser surgery, patients undergoing robotic surgery were significantly more likely to have negative margins, neck dissection, lower incomes, and care at an academic center. Rates of robotic surgery also significantly increased from 2010 to 2015. After multivariate regression, robotic surgery was associated with significantly improved overall survival compared to laser surgery and primary radiation. Robotic surgery improves overall survival for T1 and T2 hypopharyngeal tumors compared to laser surgery and primary radiation in this NCDB cohort. This effect may be mediated by decreased positive margin rates relative to laser surgery. Rates of hypopharyngeal robotic surgery are expected to increase with wider adoption of robotic platforms and may improve overall survival rates for hypopharyngeal cancer.

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A complete magnetic sentinel lymph node biopsy procedure in oral cancer patients: A pilot study

Eliane R. Nieuwenhuis, Barry Kolenaar, Alexander J.M. van Bemmel, Jurrit J. Hof, Joop van Baarlen, Anke Christenhusz, Joost J. Pouw, Bernard ten Haken, Lejla Alic, Remco de Bree

Publication date 31-07-2021


To assess the feasibility and merits of a complete magnetic approach for a sentinel lymph node biopsy (SLNB) procedure in oral cancer patients. This study included ten oral cancer patients (stage cT1-T2N0M0) scheduled for elective neck dissection (END). Superparamagnetic iron oxide nanoparticles (SPIO) were administered peritumorally prior to surgery. A preoperative MRI was acquired to identify lymph nodes (LNs) with iron uptake. A magnetic detector was used to identify magnetic hotspots prior, during, and after the SLNB procedure. The resected sentinel LNs (SLNs) were evaluated using step-serial sectioning, and the neck dissection specimen was assessed by routine histopathological examination. A postoperative MRI was acquired to observe any residual iron. Of ten primary tumors, eight were located in the tongue, one floor-of-mouth (FOM), and one tongue-FOM transition. SPIO injections were experienced as painful by nine patients, two of whom developed a tongue swelling. In eight patients, magnetic SLNs were successfully detected and excised during the magnetic SLNB procedure. During the END procedure, additional magnetic SLNs were identified in three patients. Histopathology confirmed iron deposits in sinuses of excised SLNs. Three SLNs were harboring metastases, of which one was identified only during the END procedure. The END specimens revealed no further metastases. A complete magnetic SLNB procedure was successfully performed in eight of ten patients (80% success rate), therefore the procedure seems feasible.
Recommendations for further investigation are made including: use of anesthetics, magnetic tracer volume, planning preoperative MRI, comparison to conventional technique and follow-up.

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Recurrence and malignant transformation rates of high grade oral epithelial dysplasia over a 10 year follow up period and the influence of surgical intervention, size of excision biopsy and marginal clearance in a UK regional maxillofacial surgery unit

Ciro Gilvetti, Chandni Soneji, Brian Bisase, Andrew William Barrett

Publication date 25-07-2021


To determine the overall recurrence rate (RR) and malignant transformation rate (MTR) of high grade oral mucosal epithelial dysplasias (HGOED). A clinicopathological review of records of patients diagnosed with a unifocal HGOED between 2004 and 2016 on incisional biopsy who then underwent excision. The mean duration of follow-up was 47.7 months (±29.9 SD). Full demographic, historical and histopathological data were available for 120 patients. Six were lost to follow-up after excisional biopsy. Invasive squamous cell carcinoma (SCC) was present in 19 (18.3%) excisions. HGOED affected the lateral and ventral tongue in 58% of patients. Fourteen (11.7%) were not treated surgically but kept under surveillance. The overall RR was 34.7% (33 patients) and MTR 17.8% (17 patients). Four of the 14 (28.6%) patients who had not had the HGOED excised developed SCC, by contrast to the 13 of the 106 (12.3%) who had been treated. RR was significantly associated with positive excision margins (p = 0.007; OR = 3.6) and a clinical presentation of erythroplakia (p = 0.023; OR = 1.5). MTR was significantly associated with age (p = 0.034), clinical appearance (p = 0.030), site (p = 0.007), treatment received (p = 0.012) and positive excision margins (p = 0.007). The mean time for recurrence to develop was 62 months (±31.5 SD) (range 22-144 months), that for malignant transformation was 50 months (±32.5 SD) (range 8-97 months). Patients with HGOED require follow-up for at least 10 years after treatment. Younger age, homogeneous clinical appearance, complete excision, a larger excision specimen and clear margins all improve prognosis.

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Transoral endoscopic thyroidectomy using a self-retaining retractor as an alternative to carbon dioxide gas insufflation: A comparative analysis of 131 cases

Jun-Ook Park, Dong-hyun Lee, Mi Ra Kim, Sang-Yeon Kim, Jae Hong Han, Dong-Il Sun

Publication date 04-08-2021


Although transoral endoscopic thyroid surgery affords several advantages, the use of carbon dioxide (CO2) gas to create and maintain the working space may cause complications such as subcutaneous emphysema and a CO2 embolism. We have used a self-retaining retractor as an alternative to CO2 gas insufflation for some time; we here report its feasibility and safety. We reviewed the medical records of 131 patients who underwent transoral endoscopic thyroid lobectomy; we compared the "CO2 group" and the "retractor" group. All thyroid tumors were completely removed with negative surgical margins. No major complication occurred in the retractor group.
Two major events occurred in the CO2 group: one case of permanent vocal cord palsy and one CO2 embolism. Significant subcutaneous emphysema of the neck and chest were noted in 17.7% of CO2 group patients, but in no retractor group patient. Wound infection occurred in one patient in each group but improved after appropriate management. The total operation times from incision to suture did not differ significantly between the two groups (p = 0.514). Transoral endoscopic thyroidectomy using a self-retaining retractor as an alternative to CO2 gas insufflation is feasible and safe. The superiority of transoral endoscopic thyroidectomy would be emphasized by avoiding CO2 gas insufflation, thus eliminating the risk of CO2 gas-related complications.

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The important role of cisplatin in the treatment of HPV-positive oropharyngeal cancer assessed by real-world data analysis

Irene H. Nauta, Thomas Klausch, Peter M. van de Ven, Frank J.P. Hoebers, Lisa Licitra, Tito Poli, Kathrin Scheckenbach, Ruud H. Brakenhoff, Johannes Berkhof, C. René Leemans

Publication date 27-07-2021


The prognostic advantage of human papillomavirus (HPV)-positive oropharyngeal squamous cell carcinoma (OPSCC) resulted in the initiation of treatment de-intensification studies. Two randomized controlled trials (RCTs) reported inferior survival of HPV-positive OPSCC treated with radiotherapy plus cetuximab compared to standard of care radiotherapy plus cisplatin. In this study we investigated whether the important role of cisplatin in the treatment of HPV-positive OPSCCs would also emerge from causal inference analyses of real-world data. A retrospective cohort of 263 advanced-stage OPSCC-patients from 5 European clinics was studied, treated with radiotherapy (RT) alone or cisplatin-based chemoradiotherapy (CRT) based on standard clinical indications. Causal inference was applied to adjust for treatment assignment, thereby simulating a randomized setting. Average treatment effect of concurrent cisplatin on overall survival (OS) probability was estimated using Bayesian Additive Regression Trees (BART) and Bayesian logistic regression. Significantly better survival probabilities were found for HPV-positive OPSCC treated with CRT compared to RT alone (3-year OS probability 0.961 versus 0.798, p = 0.008). This study using causal inference of retrospective patient data confirms the important role of cisplatin in the treatment of HPV-positive OPSCC. Causal inference analyses of real-world data complements the evidence from the published RCTs.

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Surgeon practice patterns in transoral robotic surgery for HPV-related oropharyngeal cancer

Celeste Kim, Eduardo Martinez, Marta Kulich, Mark S. Swanson

Publication date 24-07-2021


Analyze how otolaryngologists approach HPV-related oropharyngeal cancer in terms of patient selection for transoral surgery, perceptions of treatment related risks and benefits, and adjuvant treatment decisions. A survey on HPV-related cancer management was distributed to otolaryngologists in the US through Red Cap. Differences in responses were analyzed using Pearson's chi-squared and Fisher's exact tests. A total of 111 out of 143 (77.6%) otolaryngologists completed the survey. Overall, most prefer treating T1/T2 tumors using transoral robotic surgery (TORS) and T3 tumors through primary radiation therapy (RT), though there were significant differences between cohorts. Non-fellowship-trained surgeons and those in community practices favored RT for T1/T2 more than their fellowship-trained and academic counterparts, respectively. For adjuvant treatment, non-fellowship-trained surgeons favored adjuvant CRT, whereas fellowship-trained surgeons preferred only adjuvant RT, for patients with lymphovascular or perineural invasion, >1 lymph node involvement, or close deep margins. TORS was viewed as having less adverse sequelae (i.e. dysphagia, dysphonia, xerostomia). Though the two modalities had similar oncologic outcomes, TORS was perceived as providing better quality of life (QOL). There are variations in HPV-related OPSCC management based on surgeon background and preferences across the US. TORS and primary RT are believed to offer similar oncologic control, but the former provides lesser adverse sequelae and better QOL. Additionally, surgeon demographics (i.e. fellowship status, practice type, and region) can affect management decisions, including patient selection for TORS and adjuvant therapy decisions. Further study is required to better understand and standardize appropriate HPV-positive OPSCC management.

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Biologic and behavioral associations of estrogen receptor alpha positivity in head and neck squamous cell carcinoma

Virginia Drake, Elaine Bigelow, Carole Fakhry, Melina Windon, Lisa M. Rooper, Patrick Ha, Brett Miles, Christine Gourin, Rajarsi Mandal, Wojciech Mydlarz, Nyall London, Peter S. Vosler, Siddhartha Yavvari, Tanya Troy, Tim Waterboer, David W. Eisele, Gypsyamber DSouza

Publication date 26-07-2021


Tumor HPV status is an established independent prognostic marker for oropharynx cancer (OPC). Recent studies have reported that tumor estrogen receptor alpha (ERα) positivity is also associated with prognosis independent of HPV. Little is known about the biologic and behavioral predictors of ERα positivity in head and neck squamous cell cancer (HNSCC). We therefore explored this in a multicenter prospective cohort study. Participants with HNSCC completed a survey and provided a blood sample. Tumor samples were tested for ERα using immunohistochemistry. ERα positivity was defined as ≥1%, standardized by the American Society of Clinical Oncology/College of American Pathologists in breast cancer. Characteristics were compared with χ Of 318 patients with HNSCC, one third had ERα positive tumors (36.2%, n = 115). Odds of ERα expression were significantly increased in those with HPV-positive tumors (OR = 27.5, 95% confidence interval[CI] 12.1-62), smaller tumors (≤T2, OR = 3.6, 95% CI 1.9-7.1), male sex (OR = 2.0, 95% CI 1.1-3.6), overweight/obesity (BMI ≥ 25, OR = 1.9, 95% CI 1.1-3.3), and those married/living with a partner (OR = 1.7, 95% CI 1.0-3.0). In a multivariate model, HPV-positivity (aOR = 27.5, 95% CI 11.4-66) and small tumor size (≤T2, aOR = 2.2, 95% CI 1.0-4.8) remained independently associated with ERα status. When restricted to OPC (n = 180), tumor HPV status (aOR = 17.1, 95% CI 2.1-137) and small tumor size (≤T2, aOR = 4.0 95% CI 1.4-11.3) remained independently associated with ERα expression. Tumor HPV status and small tumor size are independently associated with ERα expression in HNSCC.

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Percutaneous endoscopic gastrostomy can improve survival outcomes in patients with N3 nasopharyngeal carcinoma undergoing concurrent chemoradiotherapy

Yun Xu, Mengwei Chen, Qiaojuan Guo, Hewei Peng, Lanyan Guo, Jingfeng Zong, He Huang, Bijuan Chen, Hanchuan Xu, Jianji Pan, Shaojun Lin

Publication date 17-07-2021


Our previous study revealed that percutaneous endoscopic gastrostomy (PEG) and intensive nutritional support may minimize body weight loss, maintain nutritional status, and offer better treatment tolerance for patients with locally advanced nasopharyngeal carcinoma (LA-NPC) during concurrent chemoradiotherapy (CCRT). This study aimed to further explore the potential long-term survival benefits of PEG in LA-NPC. Between June 1, 2010 and June 30, 2014, a total of 133 consecutive LA-NPC patients who received prophylactic PEG (pPEG) feeding before the initiation of CCRT were included. Meanwhile, an additional 133 non-PEG patients, who were matched for age; sex; and tumor, node, and metastases stage, were selected as control cohort. The log-rank test was used to compare survival distributions between groups. Multivariate prognosis analysis was conducted using a Cox's proportional hazards regression model. After a median follow-up time of 81 months (range: 4-119 months), pPEG was not associated with significant survival benefits in the whole cohort. However, the N3 NPC patients who underwent PEG had significantly higher 5-year overall survival (OS) and progression-free survival (PFS) (84.0 and 76.0%, respectively) than those who did not undergo PEG (56.7 and 45.6%, respectively; p < 0.05). Univariate and multivariate analyses demonstrated that PEG was an independent factor for N3 survival. PEG can maintain the nutritional status and improve the rate of treatment completion for LA-NPC patients who underwent CCRT, and these advantages can transfer into survival benefits in N3 NPC. Further multicenter prospective clinical trials are warranted.

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Comprehensive analysis of circRNA expression pattern and circRNA-miRNA-mRNA network in oral squamous cell carcinoma

Yuancheng Li, Linnan Gong, Na Qin, Xiaoyu Wei, Limin Miao, Hua Yuan, Cheng Wang, Hongxia Ma

Publication date 16-07-2021


CircRNAs are critical gene modulators in tumor initiation and progression. However, the expression pattern and molecular pathogenesis of circRNAs in oral squamous cell carcinoma (OSCC) are still poorly characterized. RNA sequencing with CIRCexplorer2 pipeline was performed to identify circRNAs in 46 tumor-normal paired tissues from OSCC patients. Another set of 48 head and neck squamous cell carcinoma samples from the Mi Onco Circ database were utilized as an independent validation. Of the 1276 identified high-confidence circRNAs, 154 were differentially expressed between tumor and normal tissues (log CircRNAs showed a global down-regulation pattern in OSCC tissues, and genes regulated by circRNAs primarily involved in immune and extracellular matrix pathways, which could also affect the OSCC prognosis, indicating that they may serve as potential prognostic biomarkers.

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An overview of the current clinical status of optical imaging in head and neck cancer with a focus on Narrow Band imaging and fluorescence optical imaging

Jeroen E. van Schaik, Gyorgy B. Halmos, Max J.H. Witjes, Boudewijn E.C. Plaat

Publication date 29-08-2021


Early and accurate identification of head and neck squamous cell carcinoma (HNSCC) is important to improve treatment outcomes and prognosis. New optical imaging techniques may assist in both the diagnostic process as well as in the operative setting by real-time visualization and delineation of tumor. Narrow Band Imaging (NBI) is an endoscopic technique that uses blue and green light to enhance mucosal and submucosal blood vessels, leading to better detection of (pre)malignant lesions showing aberrant blood vessel patterns. Fluorescence optical imaging makes use of near-infrared fluorescent agents to visualize and delineate HNSCC, resulting in fewer positive surgical margins. Targeted fluorescent agents, such as fluorophores conjugated to antibodies, show the most promising results.
The aim of this review is: (1) to provide the clinical head and neck surgeon an overview of the current clinical status of various optical imaging techniques in head and neck cancer; (2) to provide an in-depth review of NBI and fluorescence optical imaging, as these techniques have the highest potential for clinical implementation; and (3) to describe future improvements and developments within the field of these two techniques.

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Canadian consensus statement on the management of radioactive iodine–resistant differentiated thyroid cancer

Andrée Boucher, Shereen Ezzat, Sebastien Hotte, Irina Rachinsky, Murali Rajaraman, Dean Ruether, Sam M. Wiseman, James Brierley, Cheryl Ho, Monika Krzyzanowska, Nathan Lamond, Marie-Hélène Massicotte, Shereen Joseph, Kassey Herscovitch, Lindsey Sikora, Eric Winquist

Publication date 14-08-2021


Radioactive iodine-resistant differentiated thyroid cancer (RAIRTC) is an aggressive form of thyroid cancer that is uncommon and heterogeneous in its clinical behavior. With the emergence of more effective systemic therapy, the need for guidance in decision-making was recognized and a consensus committee of national experts was assembled. The consensus committee consisted of 13 clinicians involved in treating RAIRTC from across Canada and included endocrinologists, nuclear medicine physicians, surgeons, and radiation and medical oncologists. Domains of interest were identified by consensus, and evidence gathered using systematic reviews. Consensus recommendations for the diagnosis and management of RAIRTC were developed. It was recognized that the rarity of RAIRTC in practice and heterogeneous patterns of thyroid cancer care could limit access to effective therapy for some RAIRTC patients. This document offers guidance to manage RAIRTC patients in a multidisciplinary manner.

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Overview of oral cavity squamous cell carcinoma: Risk factors, mechanisms, and diagnostics

Ambika Chamoli, Abhishek S. Gosavi, Urjita P. Shirwadkar, Khushal V. Wangdale, Santosh Kumar Behera, Nawneet Kumar Kurrey, Kiran Kalia, Amit Mandoli

Publication date 31-07-2021


Oral cavity squamous cell carcinoma (OCSCC) is the most common malignancy of the oral cavity. The substantial risk factors for OCSCC are the consumption of tobacco products, alcohol, betel quid, areca nut, and genetic alteration. However, technological advancements have occurred in treatment, but the survival decreases with late diagnosis; therefore, new methods are continuously being investigated for treatment. In addition, the rate of secondary tumor formation is 3-7% yearly, which is incomparable to other malignancies and can lead to the disease reoccurrence. Oral cavity cancer (OCC) arises from genetic alterations, and a complete understanding of the molecular mechanism involved in OCC is essential to develop targeted treatments. This review aims to update the researcher on oral cavity cancer, risk factors, genetic alterations, molecular mechanism, classification, diagnostic approaches, and treatment.

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Management and outcome of middle ear adenomatous neuroendocrine tumours: A systematic review

M.S.D. Engel, R.J.L. van der Lans, J.C. Jansen, C.R. Leemans, E. Bloemena, B.I. Lissenberg-Witte, J.A. Rijken, C.F. Smit, E.F. Hensen

Publication date 06-08-2021


Middle ear adenomatous neuroendocrine tumours (MEANTs) are rare, unpredictable tumours. Although most MEANTs are characterized by a benign biological behaviour and indolent growth pattern, some studies have reported locally invasive and metastastic disease. Currently, the optimal management strategy for MEANTs remains subject of debate. The aim of this study is to review the literature on MEANTs with focus on its clinical characteristics, treatment strategies and outcome. A systematic review was conducted using Pub Med, Embase and Cochrane databases. A total of 111 studies comprising 198 patients with MEANT were included. Treatment modalities comprised surgery (90%), surgery with adjuvant radiotherapy (9%) and palliative (chemo)radiotherapy in (1%). Local recurrence was observed in 25% of the patients and 7% of the patients developed metastasis, over a median period of 5.7 years (range 7 months - 32 years). Twelve of 13 patients (92%) who developed metastases had a local recurrence. Four patients (2%) died of MEANT: three due to distant metastases and one due to extensive local recurrence. Reliable histopathologic predictors of outcome could not be identified. These findings indicate that the clinical presentations of MEANT vary substantially, the overall recurrence rate is considerable and initial local tumour control is paramount. Because of the unpredictable clinical course, prolonged follow-up is warranted.

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Use of rotational thromboelastometry (ROTEM®) to predict thrombotic complications of microvascular head and neck reconstruction

Katie K. Spielbauer, Jumin Sunde, Marisa Buchakjian, Keith A. Casper, Kelly M. Malloy, Chaz L. Stucken, Mark E. Prince, Andrew J. Rosko, Samuel Schechtman, Steven B. Chinn, Sathish S. Kumar, Matthew E. Spector

Publication date 06-09-2021


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What is the impact of charcoal on human health and oral carcinogenesis?

Prashanth Panta, Sravya Reddy Dhopathi, Prashanthi Reddy

Publication date 05-09-2021


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PRAME immunohistochemistry is useful in the diagnosis of oral malignant melanoma

Daniel Hovander, Joshua Allen, Dolphine Oda, Ata S. Moshiri

Publication date 29-08-2021


While the incidence of cutaneous melanoma has dramatically increased in recent years, oral malignant melanoma (OMM) remains a rare form of noncutaneous melanoma with poor survival. PRAME (PReferentially expressed Antigen in MElanoma) is reported to have diagnostic and some prognostic utility in cutaneous melanomas and some head and neck malignancies. We sought to explore the diagnostic utility of PRAME in OMM. A total of ten specimens from eight unique cases of OMM were identified from the Oral Pathology Biopsy Service (OPBS) at University of Washington School of Dentistry between 2005 and 2019. For all cases, standard histology and immunohistochemistry stains were performed, including a stain against PRAME. The diagnoses were reviewed and confirmed by two pathologists. Clinical and epidemiologic features were described. Patient ages ranged from 55 to 82. The group consisted of five males and three females. All eight cases were located on the hard palate. Six cases represented invasive melanoma while two were early melanoma in situ.
PRAME immunohistochemistry was successfully performed on seven of eight cases: six were positive (86%), one was negative (14%) and one case lacked sufficient tissue for staining. Our results suggest that PRAME immunohistochemistry may be useful in the diagnosis of OMM, including early melanoma in situ. Further studies with clinical follow-up and a larger number of cases are needed to explore prognostic value as well as the ability to distinguish between benign, intermediate and malignant melanocytic proliferations of the oral cavity.

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Oral epithelioid rhabdomyosarcoma: Report of a rare case and literature review of a distinct variant of rhabdomyosarcoma

Carla Isabelly Rodrigues-Fernandes, Celeste Sánchez-Romero, Oslei Paes de Almeida, Fábio de Abreu Alves, Elaine Judite de Amorim Carvalho, Jurema Freire Lisboa de Castro, Danyel Elias da Cruz Perez

Publication date 25-08-2021


Epithelioid rhabdomyosarcoma is a new and rare morphological variant of rhabdomyosarcoma, with only a few reports in the literature. We aimed to describe an atypical case of this variant involving the oral cavity. A 33-year-old male patient presented with an asymptomatic, gingival mass adjacent to the left maxillary canine with progressive growth over approximately 3 months. Microscopic and immunohistochemical assessment of the biopsy specimen were consistent with epithelioid rhabdomyosarcoma. After initial chemotherapy and radiotherapy, the patient had a partial response. Surgical resection was performed, followed by adjuvant chemotherapy. After local and distant recurrences, the patient died 22 months after the initial diagnosis. According to the literature, epithelioid rhabdomyosarcoma still lacks data regarding its aetiologic factors and therapeutic options. Whether this tumour is a true subtype or simply a variant of other subtypes of rhabdomyosarcoma also remains unconfirmed. Final diagnosis leads to a broad array of microscopic and immunohistochemical analyses.

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COVID-19 pandemic and lock-down protocols: Impact in an indian tertiary cancer center

Theerthika Dillibabu, Saranya Varadarajan, Thodur Madapusi Balaji, Priyanka Balakrishnan, Shashank Tangutur, Shankargouda Patil, A. Thirumal Raj

Publication date 18-08-2021


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Spindle cell squamous cell carcinoma of alveolus with heterologous mesenchymal differentiation and synchronous contralateral buccal squamous cell carcinoma in a background of oral submucous fibrosis: Recapitulation of embryonic plasticity?

Deepak Pandiar, Pratibha Ramani, Reshma Poothakulath Krishnan, Snega Thamilselvan, Deepa R. Viswasini

Publication date 10-08-2021


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Head and neck surgical oncology training in the current era of molecular oncology

Bipin T. Varghese

Publication date 08-08-2021


Lack of regional confines limits surgical oncology training, which undoubtedly is an evolving sought-after surgical super speciality programme. Training and practice of region or domain-specific surgical oncology and the recent introduction and popularization of the concept of site-specific multidisciplinary clinics practised worldwide have provided the answer to this issue in a big way. Head and Neck Surgical oncology is one of the classic examples of such developed training pathways globally.

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Response to: Should ultrasound-guided resection be the new norm for oral tongue resections?

Klijs J. de Koning, Mark A. Varvares, Robert J.J. van Es, Jan Willem Dankbaar, Gerben E. Breimer, Remco de Bree, Rob Noorlag

Publication date 07-08-2021


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Locally advanced undifferentiated sarcomatoid carcinoma of the right maxillary sinus with PDCD6-TERT fusion: A rare case report

Li Zhang, Lin Chen, Mingzhe Xiao, Xiaoqi Xie, Feng Wang

Publication date 06-08-2021


Sarcomatoid carcinoma of maxillary sinus tumor is extremely rare in head and neck tumors and has poor prognosis and frequently occurs to relapse locally after surgery. We first reported a case of locally advanced undifferentiated sarcomatoid carcinoma of right maxillary sinus with PDCD6-TERT fusion gene. The patient with a previous history of moderate alcohol drinking and smoking. The patient underwent surgical treatment. The tumor tissue using NGS analysis, no other driver gene mutations, and the PD-L1 IHC was negative. He received TPF regimen induction chemotherapy combined with anti-PD1 inhibitor and radiotherapy. The effect of treatment was good.

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A rare case of extensive gingival lymphatic malformation

Hui Xiao, Babita Pradhan, Sushmita Pradhan, Xin Ran, Lei Wang, Hong-Jie Liu, Yu-Ping Ran

Publication date 04-08-2021


Lymphatic malformation is a benign lesion, seldom affecting the gingiva. Gingival lesions are characterized by pebbly hyperplasia, occasional pain, and bleeding. The treatment for large and exceptional areas of involvement may face difficulties. Herein we report a rare case of gingival lymphatic malformation in a 10-year-old girl.

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Chondromyxoid fibroma affecting the maxilla in a 1-year-old child: Immunohistochemical analysis and literature review

Beatriz Zamboni Martins Panucci, Evânio Vilela Silva, Rafael Humberto Artero Arévalo, Ricardo Ernesto Rivera Miranda, Florence Juana Maria Cuadra Zelaya, Heitor Albergoni Silveira, Jorge Esquiche León

Publication date 29-07-2021


Chondromyxoid fibroma (CMF) is a benign chondroid/myxoid matrix-producing tumor that often develops in the long bones of young adults. CMF is rarely reported in the craniofacial skeleton, with most cases presenting with bone erosion or destruction, which may lead to a misdiagnosis. To date, approximately 129 cases of CMF in the craniofacial region have been reported, with only three cases in patients aged less than 1 year. Of these 129 cases, only 34 affected the jaws. A 1-year-old boy presented with a mass in the left anterior maxilla, extending and compressing the ipsilateral nasal cavity. After surgical excision of the lesion, microscopy revealed spindle-to-stellate tumor cells surrounded by a predominant myxoid stroma containing focal slit-like vascular channels and hemorrhagic areas. Immunohistochemistry showed positivity for vimentin, CD10, and α-SMA (focal). The Ki-67 labeling index was 6%. CFM should be included in the differential diagnosis when assessing maxillary tumors in pediatric patients.

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Covid-19 negatively impacted on small oncology surgery but none on major procedures: Regional experience

Luca DAscanio, Gino Latini, Manlio Pandolfini, AORMN Head and Neck Cancer Team, Luca Imperatori, Arianna Di Stadio

Publication date 29-07-2021


To understand the impact of COVID pandemic on the activity and patients' care of the Head and Neck regional Unit, temporary moved in a COVID-free hospital. We retrospectively analyzed the yearly activity of the "Head & Neck Cancer Unit" at the Azienda Ospedali Riuniti Marche Nord (Italy) during 2020 (COVID-19 pandemic) and we compared it with the one performed in 2019. Statistical analyses were performed using Chi-square. No significant differences were observed comparing the total number of patients treated for H&N squamous cell carcinoma (SCC) in 2019 with the ones in 2020. Moreover, no differences were identified in term of cancer stage at the moment of the surgery between 2019 and 2020. On the contrary, a significant reduction in the number of surgical procedures carried out for thyroid (p < 0.05) and skin (p < 0.001) malignancies was identified. Despite Covid-19 limitations, our institution was able to preserve the number of major oncologic procedures without negative impact on patients' care. We believe that the creation of specific COVID-free hospital can be the key preserve quality of care in epidemic emergency.

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Machine learning in head and neck cancer: Importance of a web-based prognostic tool for improved decision making

Alhadi Almangush, Rasheed Omobolaji Alabi, Antti A. Mäkitie, Ilmo Leivo

Publication date 17-07-2021


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Extent of neck dissection in the N+ neck: Adjudicating a Conundrum!

Yash P. Merchant, Akshay Kudpaje, Vishal U.S. Rao

Publication date 15-07-2021


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Are taxanes more effective than 5FU in combination chemotherapy for recurrent and metastatic head and neck cancer?

Muhammad Shahid Iqbal, Josef Kovarik, Rahul Patil, Charles G. Kelly

Publication date 14-07-2021


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Psychosocial Factors in an Oral Cancer Survivor Leading to Delay in Seeking Help

Mohammed Imaduddin, Mahesh Sultania, B. Vigneshwaran, Dillip Kumar Muduly, Madhabananda Kar

Publication date 10-07-2021


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The medial sural artery perforator flap: An underutilized flap in oral cavity reconstruction

Allen L. Feng, Hassan B. Nasser, Keith A. Casper, Kelly M. Malloy, Chaz L. Stucken, Mark E. Prince, Steven B. Chinn, Andrew J. Rosko, Matthew E. Spector

Publication date 07-07-2021


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P16-positive secondary tongue squamous cell carcinoma following allogeneic hematopoietic stem cell transplantation: A case report and literature review

Tiantian Wu, Zhenmin Liu, Xiangzhi Yong, Guocheng Mei, Qiaozhi Jiang, Meifei Fang, Ping Li, Zhongming Zhang, Renchuan Tao

Publication date 05-07-2021


As a method to improve the survival rate of patients with hematological malignancies, allogeneic hematopoietic stem cell transplantation (allo-HSCT) has increasingly been used for treatment. However, some potentially serious complications after allo-HSCT, including graft-versus-host disease, graft failure, infection, end-organ toxicity, and secondary malignancies, will determine the success of hematopoietic reconstitution. Here, we describe a case of a patient with p16-positive tongue squamous cell carcinoma (TSCC) following allo-HSCT. A 62-year-old man who had previously received allo-HSCT due to acute lymphocytic leukemia (AML) presented with erosions on the back of the tongue surrounded by multiple white patches, which were compatible with oral chronic graft-versus-host disease (cGVHD). During follow-up, a circular-like erosive lesion appeared on the right dorsal surface of the tongue. Biopsy of this lesion confirmed early invasive TSCC (T2N0M0). Partial glossectomy and tongue reconstruction were performed after cessation of immunosuppressants. Immunohistochemical (IHC) staining was positive for p16 and ki-67, suggesting a probable active human papillomavirus (HPV) infection. Six months after surgery, the patient showed no signs of metastasis or recurrence nor progression of oral GVHD.

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p16 positive oropharyngeal small cell cancer: A case report

Nada Al Masalmeh, Geetika Kukreja, Feras Zaiem, S. Naweed Raza, Harold Kim, Misako Nagasaka, Ammar Sukari

Publication date 01-07-2021


Extra-pulmonary small cell carcinomas (EPSCC) are rare malignancies. Like small cell lung cancer (SCLC), they are aggressive malignancies with dismal prognosis. We here report a case of a middle-aged man who presented with odynophagia and cervical lymphadenopathy. Diagnostic workup confirmed the diagnosis of locally-advanced p16-positive oropharyngeal cancer (OPC) with a surprising histology of small cell cancer, suggesting a human papilloma virus (HPV)-related oropharyngeal cancer with small cell differentiation. HPV oropharynx infection is a well-known risk factor for squamous cell carcinoma of the oropharynx, but it is unknown if it may increase the risk of other OPC histology.

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Should sitting time be a treatment target in head and neck cancer patients receiving curative treatment?

Ilda Patrícia Ribeiro, Teresa Lopes, Nicole Pedro, Leonor Barroso, Rui Costa, Isabel Marques Carreira, Fernando Ribeiro

Publication date 01-07-2021


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Poorly differentiated “insular” thyroid carcinoma with solitary vascular mandibular metastasis – A rare histology and management

Sachin Ambre, Mahesh Sultania, Sandhya Biswal, Suvradeep Mitra, Biswajit Sahoo, Dillip Kumar Muduly, Madhabananda Kar

Publication date 29-06-2021


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Clinical and treatment course of lung carcinoma from adult-onset recurrent respiratory papillomatosis with lung involvement: A case report

Marcelo Cardoso Figueiredo, Mariana Chantre-Justino, Rafael Latini Ruback, Paulo Pires de Mello, Gilda Alves, Maria Helena Ornellas

Publication date 26-06-2021


Neoplasms induced by human papillomavirus (HPV) infection are generally associated to high-risk HPV types. Recurrent respiratory papillomatosis (RRP) is a rare and chronic HPV-related disease characterized by papillomatous lesions in the respiratory tract, usually affecting larynx. RRP rarely comprises malignant transformation since the low-risk HPV-6 and/or HPV-11 are the most commonly found in the disease. We described a case of one adult-onset RRP (29-year-old, female) with HPV-6 infection affecting vocal folds and extra-laryngeal sites. Computed tomographic scan of the chest revealed papillomatosis with pulmonary spread showing multiple nodules and cavities. Lung involvement later progressed to squamous cell carcinoma of the lung. Patient's pregnancy during investigations may have accelerated lung carcinoma development due to immunological changes. Immunohistochemistry revealed PD-L1 high expression in tumor biopsy and, after pregnancy, the oncology treatment included a combination of pembrolizumab (PD-L1 inhibitor) to chemotherapy and also radiotherapy, showing considerable results. Patient died due to lung cancer complications 15 months after cancer diagnosis. RRP management associated with lung involvement and poor prognostic outcome, such as lung carcinoma, is still a big challenge. In this report, we described the clinical and treatment course of RRP progression to highlight the need for attention to future patients.

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Multifaceted multinucleated giant cells in oral squamous cell carcinoma

Deepak Pandiar, Pratibha Ramani, Reshma Poothakulath Krishnan, K. Monica

Publication date 26-06-2021


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Caution with carotids: A necessary cognizance

Adarsh Kudva, Vasantha Dhara, BR Patil, Mridula Sankaran

Publication date 26-06-2021


Most aberrations in the cervical course of the internal carotid artery are generally encountered as incidental findings due to their asymptomatic nature. However these morphological variations if not identified intra operatively or pre operatively may lead to vascular accidents. It is essential to be aware of the existence of tortuosity, kinking, and coiling of these great vessels while considering patients for surgeries of head and neck cancer, pharyngeal resections, traumatic injury repair, etc. Our paper presents a case series of four patients in whom carotid dolichoarteriopathies were observed during the course of neck dissection. It aims to highlight the precautions required to avoid morbidity in such patients.

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Hybrid oral potentially malignant disorder: A neglected fact in oral submucous fibrosis

Sachin C Sarode, Shailesh Gondivkar, Gargi S. Sarode, Amol Gadbail, Monal Yuwanati

Publication date 21-06-2021


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Versatility of a single piece scapular tip and lateral border free flap for mandibular reconstruction: A virtual study on angle correspondence

Khanh Linh Tran, Edward Wang, Sidney Fels, Antony Hodgson, Eitan Prisman

Publication date 19-06-2021


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Linking chronic periodontitis and oral cancer: A review

Avinash Kavarthapu, Kaarthikeyan Gurumoorthy

Publication date 19-06-2021


The aim of this article is to survey the accessible writing on the pathogenetic systems engaged with the relationship between oral malignancy and periodontitis. Gingival tissue contains multiple microbiota, which can induce inflammatory reactions. This reaction plays a crucial role in assessing the susceptibility of patients to periodontal diseases. The link between chronic periodontitis and the risk of malignancy through this inflammation of the affected epithelium have been studied thoroughly. Many studies have reported that, chronic periodontitis has systemic influence which has high risk of developing different types of cancers. Also, various confounding factors such as consumption of alcohol, smoking, diet, age and gender have been found to be associated with both chronic periodontitis and oral cancer. An online quest for a wide range of articles distributed was started utilizing MEDLINE/Pub Med, with the keywords, for example, 'oral squamous cell carcinoma (OSCC)', 'oral microbiota,' 'microorganisms and malignancy and Porphyromonas gingivalis. This review aimed to study the current literature linking chronic periodontitis and oral cancer.

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Implementation of human papillomavirus circulating tumor DNA to identify recurrence during treatment de-escalation

Catherine T. Haring, Collin Brummel, Chandan Bhambhani, Brittany Jewell, Molly Heft Neal, Apurva Bhangale, Keith Casper, Kelly Malloy, Scott McLean, Andrew Shuman, Chaz Stucken, Andrew Rosko, Mark Prince, Carol Bradford, Avraham Eisbruch, Michelle Mierzwa, Muneesh Tewari, Francis P. Worden, Paul L. Swiecicki, Matthew E. Spector

Publication date 19-06-2021


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