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Background: France has the sixth highest incidence of oropharyngeal cancer (OPC) in Europe, but the epidemiological impact of high-risk HPV (HR-HPV) remains poorly documented. The objective of our study was to assess the proportion of OPCs caused by HR-HPV in Paris, and its suburbs, over the four past decades. This area accounts for almost one-fifth of the total population of France., Methods: OPCs diagnosed in 1981, 1986, 1991, 1996, 2001, 2006, 2011, 2016 and 2020/2021 in two of the main referral cancer centers for HNCs in Paris and its suburbs were retrieved from the tumor biobanks. HPV status was determined by p16-staining and HPV-DNA detection. Samples were considered HPV-driven if both assays were positive. Results were compared to the French cancer registry data., Results: Samples from 697 OPC patients were assessed (including 82 % of all samples diagnosed in 2001, 2006, 2011, 2016, 2021). The proportion of HPV-driven cases rose from 2.7 % to 53 % between 1981 and 2021. HPV16 was the dominant genotype during the study period. Of patients with HPV-driven OPC, 81 % were male and 42 % were smokers versus 80 % and 92 % in their HPV-negative counterparts. The age of OPC patients increased significantly, during the study period, independent of their HPV status CONCLUSION: The proportion of HPV-driven OPCs has significantly increased in Paris and its suburbs, during the last four decades. OPCs has become the 2nd predominant type of head and neck cancer, in France. This may be linked to the rise in HPV-driven cases and the decrease of tobacco and alcohol consumption in men., Competing Interests: Declaration of Competing Interest The authors have nothing to disclose, (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Objectives: The management of upper aerodigestive tract cancers is a complex specialty. It is essential to provide an update to establish optimal care. At the initiative of the INCa and under the auspices of the SFORL, the scientific committee, led by Professor Béatrix Barry, Dr. Gilles Dolivet, and Dr. Dominique De Raucourt, decided to develop a reference framework aimed at defining, in a scientific and consensus-based manner, the general principles of treatment for upper aerodigestive tract cancers applicable to all sub-locations., Methodology: To develop this framework, a multidisciplinary team of practitioners was formed. A systematic analysis of the literature was conducted to produce recommendations classified by grades, in accordance with the standards of the French National Authority for Health (HAS)., Results: The grading of recommendations according to HAS standards has allowed the establishment of a reference for patient care based on several criteria. In this framework, patients benefit from differentiated care based on prognostic factors they present (age, comorbidities, TNM status, HPV status, etc.), conditions of implementation, and quality criteria for indicated surgery (operability, resectability, margin quality, mutilation, salvage surgery), as well as quality criteria for radiotherapy (target volume, implementation time, etc.). The role of medical and postoperative treatments was also evaluated based on specific criteria. Finally, supportive care must be organized from the beginning and throughout the patients' care journey., Conclusion: All collected data have led to the development of a comprehensive framework aimed at harmonizing practices nationally, facilitating decision-making in multidisciplinary consultation meetings, promoting equality in practices, and providing a state-of-the-art and reference practices for assessing the quality of care. This new framework is intended to be updated every 5 years to best reflect the latest advances in the field., (Copyright © 2024 Société Française du Cancer. Published by Elsevier Masson SAS. All rights reserved.)

Background: One of the challenges after total pharyngolaryngectomy (TPL) is to restore the swallowing function. The aim of this study was to compare swallowing outcomes between patients who underwent reconstruction with jejunum free flap (JFF) and other free flaps (OFFs)., Methods: This retrospective study included patients who underwent TPL and free flap reconstruction. The endpoints were the evolution of swallowing outcomes during the first five years after treatment assessed by the Functional Oral Intake Scale (FOIS), and outcomes associated with complications., Results: One hundred and eleven patients were included, 84 patients in the JFF group and 27 in the OFF group. The patients in the OFF group experienced more chronic pharyngostoma (p = 0.001) and pharyngoesophageal stricture (p = 0.008). During the first year, a lower FOIS score tended to be associated with OFF (p = 0.137), and this result remained stable over time., Conclusions: This study suggests that JFF reconstruction provides better swallowing outcomes than OFF reconstruction, stable over time., Competing Interests: Declaration of Competing Interest No conflict of interest statements., (Copyright © 2023 British Association of Plastic, Reconstructive and Aesthetic Surgeons. Published by Elsevier Ltd. All rights reserved.)

Objectives: To identify the factors related to the presence of occult metastases before salvage total laryngectomy (STL) in rcN0 patients and to propose an algorithm to identify patients who do not require neck dissection (ND)., Patients and Methods: This multicentric retrospective study included five centers with recruitment from 2008 to 2018. Inclusion criteria were: i) having been treated for laryngeal squamous cell carcinoma in first intention by radiotherapy (either alone or potentiated or preceded by induction chemotherapy), ii) having received STL with or without ND, iii) having an rcN0 neck at the time of STL., Results: 120 patients met the inclusion criteria. The overall rate of occult metastases was 9.1 %. The rate was significantly higher in patients with an initial positive cN+ lymph node status (p < 0.005) and in advanced stages with rcT3-T4 lesions at recurrence (p < 0.005). Patients with occult metastases recurred earlier than those without (p = 0.002). The overall survival of patients was the same with or without ND (p = 0.16). There were significantly more healing complications requiring revision surgery in the group with ND than in the group without (p = 0.048)., Conclusion: ND does not confer a net survival benefit and is associated with significant complications. Patients without initial lymph node metastases who are rcT1-T2 at recurrence or rcT3-T4 with a recurrence period of more than 12 months could benefit from STL without ND. This decisional algorithm, which needs to be validated, would help avoid 58 % of ND procedures and their proven morbidity., Discipline: Head and neck surgery., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Objective: We investigated the quality of life (QoL), functional, and oncological outcomes after robotic-assisted transoral or combined cervical-transoral salvage surgery for oropharyngeal carcinoma following radiotherapy., Material and Methods: We performed a single tertiary referral center, prospective, observational cohort study of all consecutive patients who underwent salvage robotic-assisted surgery for oropharyngeal carcinoma between 2015 and 2021. The primary outcomes were quality of life assessments using the MDADI, EORTC-QLQC30, and EORTC-QLQH&N35. Secondary endpoints were the functional and oncological outcomes based on overall survival, disease-free survival, and local control., Results: A consecutive cohort of 53 patients were included. The median Charlson comorbidity index was 5. The p16 status was negative in 87%, and 22.6% were T3-4. A flap reconstruction was performed in 90.6%, with a free flap in 67.9%. Margins were negative in 81.1%. The preoperative, 1-year, and 2-year MDADI total scores were 71.4, 64.3, and 57.5, respectively. The preoperative, 1-year, and 2-year QLQ-C30 global scores were 61.2, 59.4, and 80.6, respectively. Decannulation was possible in 97.1% of the tracheotomized patients. The two-year enteral tube dependence was 23.1%. The two-year overall survival, disease-free survival, and local control rates were 59%, 46.1%, and 80.9%, respectively., Conclusion: Robotic-assisted salvage surgery for oropharyngeal carcinoma following radiotherapy demonstrated a very satisfactory quality of life, good functional sequelae, and good oncological outcomes compared to historical approaches., Competing Interests: Declaration of competing interest VP and PG declare that they are Proctors for Intuitive Surgical. Other authors have no conflict of interest to disclose., (Copyright © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.)

The COVID-19 pandemic has a major impact at all stages of cancer treatment. Risk of death from COVID-19 in patients treated for a cancer is high. COVID-19 vaccines represent a major issue to decrease the rate of severe forms of the COVID-19 cases and to maintain a normal cancer care. It is difficult to define the target population for vaccination due to the limited data available and the lack of vaccine doses available. It appears theoretically important to vaccinate patients with active cancer treatment or treated since less than three years, as well as their family circle. In France, patients actually defined at "high risk" for priority access to vaccination are those with a cancer treated by chemotherapy. A panel of experts recently defined another "very high-priority" population, which includes patients with curative or palliative first or second-line chemotherapy, as well as patients requiring surgery or radiotherapy involving a large lung volume, lymph nodes and/or of hematopoietic tissue. Ideally, it is best to vaccinate before cancer treatment. Despite the lack of published data, COVID-19 vaccines can also be performed during chemotherapy by avoiding periods of bone marrow aplasia and if possible, to do it in cancer care centers. It is necessary to implement cohorts with immunological and clinical monitoring of vaccinated cancer patients. To conclude, considering the current state of knowledge, the benefit-risk ratio strongly favours COVID-19 vaccination of all cancer patients., (Copyright © 2021 Société Française du Cancer. Published by Elsevier Masson SAS. All rights reserved.)

Background: Among patients with T0-2 N3 head and neck squamous cell carcinomas (HNSCC), those undergoing upfront neck dissection have better oncological outcomes. However, there is no consensual definition of disease resectability of N3 nodes, leading to major treatment attrition and interpretation biases between studies. We established a Delphi method-based consensus to define resectability and impact on decision-making for upfront neck dissection in N3 patients., Methods: The Delphi method was designed as recommended by the French Haute Autorite de Sante among head and neck surgeons from university hospitals and cancer centers, using a 24-item questionnaire. Strong and relative agreements were subsequently established, and recommendations were written. The resulting recommendations were assessed by 30 independent surgeons., Results: N3 nodes with intraparenchymal brain invasion, foramen invasion, skull base erosion, nodes requiring bilateral XII th cranial nerve sacrifice, retropharyngeal N3 node or a node above the plan of soft palate are major contraindications to neck dissection. When neck dissection requires unilateral sacrifice of the IX th or X th or XII th cranial nerves or cervical nerve roots, upfront neck dissection may be performed, based on a case-by-case assessment of other patient and tumor estimates., Conclusion: Consensual contraindications to neck dissection in patients with T0-2 N3 HNSCC were defined among French head and neck surgeons as concerns skull base invasion, retropharyngeal nodes and bilateral XII th cranial nerve sacrifice. This consensus should allow more reliable comparisons between surgical and non-surgical strategies in N3 patients., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Background: Salvage surgeries are challenging procedures, with an associated poor prognosis. Management of the N0 neck in those situations remains controversial. We aim to compare oncologic outcomes regarding neck management after surgery for N0 pharyngo-laryngeal carcinoma occurring after loco-regional radiotherapy., Methods: We conducted a multicentric retrospective study, including all patients undergoing surgery for persistent, recurrent or new primary N0 carcinoma of the oropharynx, hypopharynx or larynx between 2005 and 2015, following loco-regional radiotherapy., Results: A total of 239 patients were included, concerning respectively 44%, 34% and 22% oropharyngeal, laryngeal and hypopharyngeal tumors operated. A neck dissection was performed in 143 patients (60%), with an occult nodal metastasis rate of 9%. This rate was higher for hypopharyngeal carcinomas (18%, p = 0.16) and tumors with initial nodal involvement (16%, p = 0.05). With a median follow-up of 60 months, the median overall survival (OS) and progression-free survival rates (PFS) were 34 months and 25 months. We identified negative margin excision status, age at the time of surgery (under 60) and delay between RT and surgery over 2 years as the only variables associated with better OS (p < 0.0001 and p = 0.004) and PFS (p < 0.0001 and p = 0.010) in multivariable analysis, with no difference regarding neck management. Regional progression (alone or with distant metastasis) was noted in 10 cases: 4 in the neck observation group (4%) versus 6 in the neck dissection group (4%)., Conclusion: Elective lymph node dissection of irradiated neck should not be routinely performed in patients undergoing surgery for persistent, recurrent or new primary pharyngo-laryngeal carcinomas., Competing Interests: Declaration of competing interest None, (Copyright © 2020. Published by Elsevier Ltd.)

Sentinel lymph node biopsy (SLNB) has been initially developed for melanoma and breast cancers. Its application in head and neck cancers is recent, probably due to the complexity of the lymphatic drainage, the proximity between the primary tumor and the lymph nodes and the critical anatomical structures (such as the facial nerve). In onco-dermatology, SLNB is validated in head and neck surgery for melanoma with Breslow thickness up to 1mm or ulceration, Merkel carcinoma and high-risk squamous cell carcinoma. Considering the malignancies of the upper aerodigestive tract, the feasibility and oncologic safety of SLNB are now established for T1-T2N0 oral and oropharyngeal squamous cell carcinomas. Thus, it could allow patients with negative sentinel nodes to avoid an unnecessary neck dissection, leading to a decrease of morbidity with an quality of life improvement. For some primary locations (e.g., anterior floor of the mouth) with high proximity between tumor and lymph nodes, it is recommended to remove the tumor before the SLNB so as to improve the detection. New techniques of detection are currently being developed with intra-operative procedures and new tracers (such as tilmanocept), leading to a better accuracy of detection and, probably, new indications., (Copyright © 2019 Société Française du Cancer. Published by Elsevier Masson SAS. All rights reserved.)

Background: The objective of this study was to conduct a systematic review and meta-analysis of the incidence of positive surgical margins after transoral surgery for oropharyngeal carcinoma, as well as the factors associated with positive margins and their impact on local tumor control., Method: An electronic search of English-language literature databases was conducted, and a systematic review was performed in accordance with the PRISMA guidelines., Results: A total of 42 articles were included in the analysis. The overall rate of positive margins using transoral conventional surgery (CTS), transoral laser microsurgery (TLM), or transoral robotic surgery (TORS) was 7.8% in a cumulative total of 3619 patients. A positive margin status was associated with a reduction in local control. Assessment of intraoperative frozen sections was associated with a reduced risk of definitive positive margins, whereas a T4 classification was associated with an increased risk of definitive positive margins. Neither the primary site (the tonsillar fossa versus the base of the tongue), nor the HPV status, were associated with the margin status. The level of heterogeneity between the various studies was very high., Conclusion: The currently used transoral procedures are safe in regard to proper tumor resection and they should continue to be part of the armamentarium of surgical techniques used in head and neck surgery. The very high level of heterogeneity between studies calls for a definition consensus for margin status assessments in transoral surgery., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Background: Head and neck mucosal melanoma (HNMM) is a rare and aggressive disease with a high metastatic potential. Two staging systems are currently available: one specific to HNMM (mmTNM) and one specific to primary tumour sites (sccTNM). Our main objective was to assess the prognostic value of both of these classifications in order to allow accurate risk-based classification., Methods: We performed a retrospective cohort study of patients with HNMM treated consecutively between 2000 and 2017. All of the patients were restaged using the mmTNM and the sccTNM. A prognostic analysis was carried out according to both staging systems., Results: There were 96 patients with an HNMM in our cohort, of whom 80 underwent surgical treatment followed by radiotherapy. The median overall survival (OS) and progression-free survival (PFS) for the operated patients were 39 months (95% CI, 21.6-56.4 months) and 18 months (95% CI, 6.5-29.5 months), respectively. A paranasal sinus localization was associated with lower survival compared to a nasal cavity primary localization (p < 1 0 -4 ). Both of the classifications correlated with OS, PFS, and distant metastasis-free survival. High-risk HNMM were characterized as T4/stage IV by the mmTNM and T3-4/stage III-IV by the sccTNM. Given the primary tumour location, both TNM classifications were suitable for risk-stratification of sinonasal mucosal melanomas. However, combining both TNM, we defined new stages mmT3A and mmT3B according to sccTNM with a more accurate risk stratification (p < 1 0 -4 )., Conclusions: Both of the classifications should be combined, in order to improve the risk-stratification of patients with HNMM., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Objectives: After induction chemotherapy (IC) for laryngeal cancer, Computed Tomography (CT) is used to assess tumor response but lacks rationalized methods for measurement of this response. In T3 laryngeal cancer, remobilization of an initially fixed vocal cord (VC) is a major sign of tumor response. We compared the performances of RECIST1.1, WHO and volumetric methods of evaluating response with laryngeal remobilization to determine if these measurements could objectively assess tumor response., Material and Methods: This monocentric retrospective cohort study included patients treated with T3 laryngeal cancer with initial VC fixation treated with an organ preservation protocol with IC between 1999 and 2012. Tumors were measured with CT using RECIST1.1, WHO and volumetric methods by two radiologists blinded to VC remobilization (VCR), before and after induction chemotherapy and VC mobility was clinically assessed. Radiologic tumor shrinkage was compared to VCR. AUCs of ROC curves were compared. Inter-reader reliability, sensitivity and specificity of optimal cutoffs were determined., Results: Seven females and thirty-six males with a mean age of 59 years were included. AUCs were 0.759, [95%CI 0.614; 0.904] for RECIST1.1, 0.763, [95%CI 0.617; 0.909] for WHO and 0.752, [95%CI 0.608; 0.896] for volumetric evaluations with no significant difference among the three techniques. Inter-reader reader reliabilities were good (RECIST1.1) to excellent (WHO and volumetric methods)., Conclusion: RECIST1.1, WHO and volumetric measures match with VCR after IC in patient with T3 laryngeal cancer. WHO criteria combine accuracy, reproducibility and practical use; they may be best adapted for response assessment and protocol design., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Introduction: HPV-driven oropharyngeal cancer (OPC) patients have a better prognosis than their HPV-negative counterparts but several studies have suggested that among HPV-positive patients those with a smoking history had worse oncological outcomes. The aim of our study is to characterize the interplay between tobacco consumption, patient and disease characteristics, and disease control., Materials and Methods: All patients diagnosed with HPV-driven OPC and treated with curative intent between 2007 and 2009 and 2011-2016 at Gustave Roussy cancer center were included (n = 282). Demographic, clinical, morphological and tobacco consumption were correlated with oncologic outcomes., Results: 157 (56%) patients had a positive smoking history, including 23.8% who were smoking at the time of diagnosis and 37.6% who had a tobacco consumption exceeding 20 pack-years. In multivariate analysis, the strongest prognostic factor for survival was smoking status at cancer diagnosis, with a hazard ratio (HR) for non-smokers compared to smokers of 0.25 ([0.12, 0.50], p = 0.0001). Smoking history, either more than 20 pack-years or smoking at diagnosis, was associated with local relapse and distant relapse. There was no difference in terms of comorbidity (p = 0.32) and radiotherapy duration (p = 0.93) according to tobacco consumption., Discussion: Smoking is frequent among patients with HPV-driven OPC and increases the risk of death and oncologic failure., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Objectives: To explore prognostic and predictive value of radiomics in patients with locally advanced head and neck squamous cell carcinomas (LAHNSCC) treated with concurrent chemoradiotherapy (CRT) or bioradiotherapy (BRT)., Materials and Methods: Data of 120 patients (CRT vs. BRT matched 2:1) were retrospectively analyzed. A total of 544 radiomics features of the primary tumor were extracted from radiotherapy planning computed tomography scans. Cox proportional hazards models were used to examine the association between survival and radiomics features with false discovery rate correction. The discriminatory performance was evaluated using receiver operating characteristic curve analysis., Results: Multivariate analysis showed a 24-feature based signature significantly predicted for OS (HR=0.3, P=0.02) and progression-free survival (PFS) (HR=0.3, P=0.01). Combining the radiomics signature with p16 status showed a significant improvement of prognostic performance compared with p16 (AUC=0.78vs. AUC=0.64 at 5years, P=0.01) or radiomics signature (AUC=0.78vs. AUC=0.67, P=0.01) alone. When patients were stratified according to this combination, OS and PFS were significantly different according to the 4 sub-types (p16+ with low/high signature score; p16- with low/high signature score) (P<0.001). Patients with high signature score significantly benefited from CRT (vs. BRT) in terms of OS (P=0.004), while no benefit from CRT in patients with low signature score., Conclusion: Our analysis suggests an added value of radiomics features as prognostic and predictive biomarker in HNSCC treated with CRT/BRT. Moreover, the radiomics signature provided additional information to HPV/p16 status to further stratify patients. External validation of such findings is mandatory given the risk of overfitting., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Background: Poor prognosis of sinonasal cancers (SNC) is usually due to the non-specific symptoms leading to late diagnosis with locally advanced disease. However, previous prognostic studies were often based on heterogeneous cohorts because of the scarcity of SNC. With squamous cell carcinoma being the main histological subgroup, the study aimed to perform a prognostic analysis on sinonasal squamous cell carcinoma (SNSCC) particularly, and to evaluate the oncological results of a multimodal therapy., Methods: A retrospective review of 68 cases involving SNSCC treatment between 1998 and 2012 at Gustave Roussy Cancer Campus was performed. Clinical, pathological, and treatment characteristics were evaluated as prognostic markers for oncological outcomes., Results: The 5-year overall survival (OS) and progression-free survival (PFS) rates were 58.1% and 52.6% respectively. Tumor downsizing under neoadjuvant chemotherapy (NACT) was observed in 82.5% of cases. The main pattern of recurrence was local with a 2- and 5-year rate of 37.3%. Decreased OS, PFS and local control were associated with involvement of the orbit, the soft tissue, and the suprastructure (p < 0.005)., Conclusion: Prognosis of surgically treated SNSCC remains poor. Multimodal treatment combining NACT followed by wide resection requiring complex reconstruction and adjuvant radiation therapy seems to provide promising results., (Copyright © 2017 European Association for Cranio-Maxillo-Facial Surgery. Published by Elsevier Ltd. All rights reserved.)

Objectives: To evaluate the efficacy of induction chemotherapy with docetaxel, cisplatin and fluorouracil (TPF) followed by concurrent chemoradiotherapy (IC+CCRT) or CCRT alone in non-endemic locally advanced nasopharyngeal carcinoma (NPC) patients., Materials and Methods: Data of 106 patients with NPC treated from January 1999 to June 2012 with IC+CCRT (n=58) or CCRT alone (n=48) were retrospectively reviewed., Results: Median follow-up was 6.4years. Distribution of age, performance status, stage and concurrent chemotherapy regimen were imbalanced between the two groups. The 5-year overall survival (OS) and progression-free survival (PFS) were not significantly different between IC+CCRT and CCRT groups (OS: 78.3% vs. 82.7%, p=0.77; PFS: 72.5% vs. 68.2%, p=0.81, respectively). There were less total cumulative incidence of grade 3-4 late radiation morbidity in the IC+CCRT group (44.8% vs. 70.8%, p=0.01). Five-year OS for patients with post-IC complete response (CR), partial response (PR) and stable disease (SD) sub-groups were 100%, 79.4% and 60%, respectively., Conclusion: Compared with CCRT alone, IC (TPF regimen)+CCRT did not improve OS or PFS in patients with NPC, but less grade 3-4 late toxicities were observed. Responsiveness of IC may provide additional prognostic information., (Copyright © 2016 Elsevier Ltd. All rights reserved.)