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Introduction: Hypopharyngeal cancer (HC) is an aggressive and life-threatening malignancy that requires a complex multimodal treatment. The aims of the present study were to analyze, in locally advanced HC patients, the oncologic and swallowing outcomes and their predictive factors according to the therapeutic strategy., Methods: All patients with locally advanced HC (T3/T4, N0-3, M0) treated at our institution between 2000 and 2020 were included in this retrospective study. Patients were classified in 3 groups according to the therapeutic strategy: primary radical surgery (RS), induction chemotherapy (ICT) or definitive (chemo)-radiation therapy ((C)RT). Predictive factors of oncologic outcomes (overall, cause-specific and recurrence-free survival: OS, CSS and RFS) and swallowing outcome (dysphagia outcome and severity scale: DOSS) were investigated in univariate and multivariate analysis., Results: A total of 217 patients were included in this study (RS: 40; ICT: 106; (C)RT: 71). 5-year OS, CSS and RFS rates were 36, 38 and 32%, respectively. ICT was associated with improved oncologic and swallowing outcomes in univariate analysis. After multivariate analysis, patient age ≥ 70 years (p = 0.0002) was the only factor significantly associated with a worse OS, whereas patient age ≥ 70 years (p = 0.002) and N stage ≥ 2 (p = 0.01) were significantly associated with a worse CSS. Comorbidity level (KFI ≥ 2; p = 0.01) and N stage (≥ 2; p = 0.02) were significantly associated with worse swallowing outcomes., Conclusion: In selected locally advanced HC patients, an ICT-based therapeutic strategy offers acceptable oncologic and functional outcomes. Patient age, N stage and comorbidity level are the main determinants of oncologic and functional outcomes., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Purpose: After the 2 years of follow-up, we aimed to evaluate at 5 years the impact of human papillomavirus (HPV) status, tobacco, and initial treatment approach on progression-free survival (PFS) and overall survival (OS) of patients with oropharyngeal cancer (OPC) in France., Methods: Papillophar study was designed as a prospective cohort of 340 OPC patients in 14 French hospitals. HPV-positive status (21.7%) was defined with PCR (positivity for HPV DNA and E6/E7 mRNA). Cox proportional hazard models were used to assess the relationship between PFS, OS, HPV, and other prognostic factors. The combined effect of HPV status with smoking, stage, or initial treatment on PFS was also evaluated., Results: HPV-pos patients had better PFS than HPV-neg patients (HR = 0.46; 95% CI: 0.29-0.74), and worse for older patients (HR for 5-year age increase = 1.14), UICC stage 4 from the 7th TNM classification compared to stage 1-2 (HR = 2.58; CI: 1.33-5.00), and those having had radiotherapy (HR = 2.07; 95% CI: 1.36-3.16) or induction chemotherapy (HR = 2.11; 95% CI: 1.32-3.38) instead of upfront surgery. HPV-neg patients encountered a larger incidence of loco-regional disease than HPV-pos patients (31.5% and 14.0%, respectively, p = 0.0001). Distant metastases proportion was similar. HPV-neg patients developed more second primary tumor than HPV-pos patients (11.7% vs. 3.3%, p = 0.02)., Conclusions: 5-year follow-up confirms the specifically improved prognosis in HPV-positive patients. The prognosis is nevertheless significantly modified through clinical and therapeutical variations., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Introduction: Patients with oropharyngeal squamous cell carcinoma (OPSCC) display a significant risk to develop a metachronous second primary neoplasia (MSPN). HPV and non-HPV-related OPSCC are 2 distinct entities with biological, clinical and prognostic differences. The aims of our study were to analyze the impact of tumor HPV status and other relevant clinical factors, such as tobacco and/or alcohol (T/A) consumption, on the risk and distribution of MSPN in OPSCC patients and to assess the impact of MSPN on patient survival., Material and Methods: All OPSCC patients treated from 2009 to 2014 were included in this multicentric retrospective study. P16 immunohistochemical expression was used as a surrogate maker of tumor HPV status. The impact of tumor p16 status on the risk of MSPN was assessed in uni- and multivariate analyses. Overall survival (OS) was determined by Kaplan-Meier analysis., Results: Among the 1291 patients included in this study, 138 (10.7%) displayed a MSPN which was preferentially located in the head and neck area (H&N), lung and esophagus. Multivariate analyses showed that p16- tumor status (p = 0.003), T/A consumption (p = 0.005) and soft palate tumor site (p = 0.009) were significantly associated with a higher risk of MSPN. We found no impact of p16 tumor status on the median time between index OPSCC diagnosis and MSPN development, but a higher proportion of MSPN arising outside the H&N, lung and esophagus was found in p16 + than in p16- patients. MSPN development had an unfavorable impact (p = 0.04) on OS only in the p16 + patient group., Conclusion: P16 tumor status and T/A consumption were the main predictive factors of MSPN in OPSCC patients. This study provides crucial results with a view to tailoring global management and follow-up of OPSCC patients., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Since there is no published randomized study comparing surgical and non-surgical therapeutic strategies in patients with oropharyngeal squamous cell carcinoma (OPSCC), the therapeutic management of these patients remains highly controversial. While human papillomavirus (HPV)-positive and HPV-negative OPSCC are now recognized as two distinct diseases with different epidemiological, biological, and clinical characteristics, the impact of HPV status on the management of OPSCC patients is still unclear. In this review, we analyze the current therapeutic options in patients with OPSCC, highlighting the most recent advances in surgical and non-surgical therapies, and we discuss the impact of HPV status on the therapeutic strategy.

Objective: To assess long-term functional and quality of life (QoL) outcomes and their predictive factors in laryngectomized patients after successful voice restoration using tracheoesophageal prostheses (TEP)., Methods: This cross-sectional study was conducted in alive and disease-free patients at least 1 year after total laryngectomy ± partial pharyngectomy. Patients completed the European Organization for Research and Treatment of Cancer (EORTC) Core (QLQ-C30) and Head and Neck Cancer (QLQ-H&N35) QoL questionnaires, the Voice Handicap Index (VHI-10) questionnaire and the Hospital Anxiety and Depression Scale (HADS). The level of dysphagia was evaluated using the Dysphagia Handicap Index (DHI) and the Dysphagia Outcomes and Severity Scale (DOSS). Predictive factors of these clinical outcomes were determined in univariate and multivariate analysis., Results: A total of 48 patients were included in this study. Long-term QoL and functioning scales scores were all superior to 70%. Main persistent symptoms were fatigue, dyspnea, senses, speech and coughing problems. A DOSS score ≥6, indicating normal/subnormal swallowing function, and a VHI-10 score ≤20, representing light to medium voice disorders, were found in at least 75% of patients. An anxiodepressive disorder (HADS global score ≥ 15) was reported by 15 (31%) patients and represented the main predictor of QoL and voice outcomes. A strong correlation was found between VHI-10 and global QoL scores., Conclusions: After successful voice restoration, laryngectomized patients achieved satisfactory QoL and functional outcomes. Psychological distress was the main determinant of long-term QoL and is therefore of critical importance in the multidisciplinary management of laryngectomized patients., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Objectives: To assess patient needs and concerns after head and neck squamous cell carcinoma (HNSCC) treatment and their possible correlations with long-term quality of life (QoL) and to examine the potential impact of psychological distress on these results., Methods: Alive and disease-free HNSCC patients at least 1 year after treatment were enrolled in this cross-sectional multicentric study and completed the EORTC QLQ-C30 and H&N35 QoL questionnaires, the head and neck cancer-specific patient concerns inventory (PCI-HN) questionnaire and the hospital anxiety and depression scale (HADS). Correlations between QoL outcomes and patient needs and concerns were investigated using Spearman's correlation tests., Results: Seventy-two patients were enrolled in the study. Fear of cancer recurrence was the main patient concern followed by dental, salivary, fatigue, speech, and eating problems. The leading patient needs in terms of consultation were to be referred to the surgeon, the speech, and swallow therapist and the oral rehabilitation team. The number of patient concerns correlated negatively (r < .40) with functioning scales score and positively (r > .40) with general and head and neck symptoms. Psychological distress was the main determinant of QoL outcomes (p < .0001). We found a significant impact of gender (p = .002) on the number of patient concerns, and of patient age (p = .003) on the number of staff members selected by patients., Conclusion: Identification of patient needs and concerns along with multidisciplinary management of persistent symptoms and psychological distress seem essential steps towards improving QoL of HNSCC patients.

Background: The aim of this study was to assess the impact of the initial therapeutic strategy on oncologic outcomes in patients with HPV-positive OPSCC., Methods: All p16-positive OPSCCs treated from 2009 to 2014 in 7 centers were retrospectively included and classified according to the therapeutic strategy: surgical strategy (surgery ± adjuvant radiotherapy and chemotherapy) vs. non-surgical strategy (definitive radiotherapy ± chemotherapy). Univariate, multivariate propensity score matching analyses were performed to compare overall (OS), disease-specific (DSS) and recurrence-free survival (RFS)., Results: 382 patients were included (surgical group: 144; non-surgical group: 238). Five-year OS, DSS and RFS were 89.2, 96.8 and 83.9% in the surgical group and 84.2, 87.1 and 70.4% in the non-surgical group, respectively. These differences were statistically significant for DSS and RFS after multivariate analysis, but only for RFS after propensity score matching analysis., Conclusion: In p16+ OPSCC patients, upfront surgery results in higher RFS than definitive radiotherapy ± chemotherapy but does not impact OS., (Copyright © 2020 Elsevier Ltd, BASO ~ The Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved.)

Introduction: Therapeutic management of oropharyngeal squamous cell carcinomas (OPSCC) is still debated. Since the role of HPV was demonstrated, few studies have focused on HPV-negative OPSCC. The aim of our study was to assess the impact of therapeutic strategy (surgical vs. non-surgical) on oncologic outcomes in patients with HPV-negative OPSCC., Material and Method: All p16-negative OPSCCs treated from 2009 to 2014 in 7 tertiary-care centers were included in this retrospective study and were classified according to the therapeutic strategy: surgical strategy (surgery ± adjuvant radiotherapy and chemotherapy) vs. non-surgical strategy (definitive radiotherapy ± chemotherapy). Patients not eligible for surgery (unresectable tumor, poor general-health status) were excluded. Univariate, multivariate and propensity score matching analyses were performed to compare overall (OS), disease-specific (DSS) and recurrence-free survival (RFS)., Results: Four hundred seventy-four (474) patients were included in the study (surgical group: 196; non-surgical group: 278). Five-year OS, DSS and RFS were 76.5, 81.3 and 61.3%, respectively, in the surgical group and 49.9, 61.8 and 43.4%, respectively, in the non-surgical group. The favorable impact of primary surgical treatment on oncologic outcomes was statistically significant after multivariate analysis. This effect was more marked for locally-advanced than for early-stage tumors. Propensity score matching analysis confirmed the prognostic impact of primary surgical treatment for RFS., Conclusion: Therapeutic strategy is an independent prognostic factor in patients with p16-negative OPSCC and primary surgical treatment is associated with improved OS, DSS and RFS. These results suggest that surgical strategy is a reliable option for advanced stage OPSCC., 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, BASO ~ The Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved.)

Introduction: Patients with oropharyngeal squamous cell carcinoma (OPSCC) display a significant risk of synchronous primary neoplasia (SPN) which could impact their management. The aims of this study were to evaluate the risk and distribution of SPN in OPSCC patients according to their HPV (p16) status, the predictive factors of SPN and the impact of SPN on therapeutic strategy and oncologic outcomes., Material and Methods: All OPSCC patients treated from 2009 to 2014 were included in this multicentric retrospective study. Univariate analyses were conducted using Chi-2 and Fisher exact tests. For multivariate analyses, all variables associated with a p ≤ 0.10 in univariate analysis were included in logistic regression models., Results: Among the 1291 patients included in this study, 75 (5.8%) displayed a SPN which was preferentially located in the upper aerodigestive tract, lung and esophagus. Comorbidity level (p = 0.03), alcohol (p = 0.005) and tobacco (p = 0.01) consumptions, and p16 tumor status (p < 0.0001) were significant predictors of SPN. In multivariate analysis, p16+ status was significantly associated with a lower risk of SPN (OR = 0.251, IC95% [0.133;0.474]). Patients with a SPN were more frequently referred for non-curative treatment (p = 0.02). In patients treated with curative intent, there was no impact of SPN on the therapeutic strategy (surgical vs. non-surgical treatment). We observed no overall survival differences between patients with or without SPN., Conclusion: P16 tumor status is the main predictive factor of SPN in OPSCC patients. This study provides crucial results which should help adapt the initial work-up and the global management of OPSCC patients., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Introduction: Although Human Papilloma Virus (HPV)-driven oropharyngeal cancer (OPC) prognosis is significantly better than that of other head and neck cancers, up to 25% of cases will recur within 5 years. Data on the pattern of disease recurrence and efficiency of salvage treatment are still sparse., Material and Method: Observational study of all recurrent OPCs diagnosed, following a curative intent treatment, in seven French centers from 2009 to 2014. p16 Immunohistochemistry was used to determine HPV status. Clinical characteristics, distribution of recurrence site, and treatment modalities were compared by HPV tumor status. Overall survival was examined using Kaplan-Meier and multivariate Cox regression modeling., Results: 350 recurrent OPC patients (246 p16-negative and 104 p16-positive patients). The site of recurrence was more frequently locoregional for p16-negative patients (65.4% versus 52.9% in p16-positive patients) and metastatic for p16-positive patients (47.1% versus 34.6% in p16-patients, p = 0.03). Time from diagnosis to recurrence did not differ between p16-positive and p16-negative patients (12 and 9.6 months, respectively, p-value = 0.2), as the main site of distant metastasis (all p-values ≥0.10). Overall and relapse-free survival following the first recurrence did not differ according to p16 status (p-values from log-rank 0.30 and 0.40, respectively). In multivariate analysis, prognosis factors for overall survival in p16-negative patients were distant metastasis (HR 2.11, 95% CI 1.30-3.43) and concurrent local and regional recurrences (HR 2.20, 95% CI 1.24-3.88)., Conclusion: With the exception of the initial site of recurrence, the pattern of disease relapse and the efficiency of salvage treatment are not different between p16-positive and negative OPCs., Competing Interests: Conflict of interest statement All the authors do not have conflict of interest., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Objectives: To assess the factors associated with long-term quality of life (QoL) and patient concerns in elderly oral or oropharyngeal cancer (OOPC) patients after oncologic surgery and free-flap reconstruction., Methods: Patients aged over 70 years who were still alive and disease-free at least 1 year after surgery were enrolled in this cross-sectional multicentric study. Patients completed the EORTC QLQ-C30, -H&N35 and -ELD14 QoL questionnaires, and the Hospital Anxiety and Depression Scale (HADS). Patient needs were evaluated using the Patient Concerns Inventory (PCI). Factors associated with these clinical outcomes were determined in univariate and multivariate analysis., Results: Sixty-four patients were included in this study. Long-term QoL, functioning scales and patient autonomy were well-preserved. Main persistent symptoms were fatigue, constipation and oral function-related disorders. Salivary and mastication/swallowing problems were the main patient concerns. The mean number of patient concerns increased with the deterioration of their QoL. Psychological distress (HADS score ≥ 15) and patient frailty (G8 score < 15) were significantly associated with poor QoL outcomes., Conclusions: We found a negative correlation between the number of patient concerns and QoL. Dental rehabilitation and psychological and nutritional supportive measures are of critical importance in the multidisciplinary management of elderly OOPC patients., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Introduction: The proportion of elderly patients with head and neck cancer is increasing. However, predictive factors of postoperative outcomes are insufficiently explored in this population. In this study, we aimed to determine predictive factors of postoperative outcomes in elderly patients undergoing head and neck free-flap reconstructive surgery in order to determine criteria on which patient selection could be based., Methods: All patients aged 65 years or over who underwent head and neck free-flap reconstructive surgery at our institution, between 2000 and 2016, were included in this retrospective study. Predictive factors of postoperative outcomes were investigated in uni- and multivariate analysis., Results: Two-hundred patients were included in the study. Older age (>70, >75 or > 80 yrs) had no significant impact on postoperative outcomes. Free flap failure local and general complications rates were 11%, 34% and 43%, respectively. Oromandibular reconstruction (p = 0.04) was significantly associated with free flap failure and salvage surgery (p = 0.04) with local complications. A high comorbidity level (Charlson Comorbidity Index score ≥ 4; p = 0.02) was associated with a higher risk of general complications. A G8 (Geriatric 8 questionnaire) score < 15 (p = 0.004), a high comorbidity level (Kaplan-Feinstein Index score ≥ 2; p = 0.04) and oromandibular reconstruction (p = 0.04) were associated with poor swallowing function at 6 months., Conclusion: Head and neck free flap reconstruction should be offered to fit (G8 score ≥ 15) elderly patients without severe comorbidities (KFI < 2 or CCI < 4), particularly when oral/pharyngeal soft-tissue reconstruction is planned., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

In this article, we aimed to discuss the role of total laryngectomy (TL) in the management of patients with larynx cancer (LC) in the era of organ preservation. Before the 1990s, TL followed by radiotherapy (RT) was the standard treatment for patients with locally advanced LC. Over the last 30 years, various types of larynx preservation (LP) programs associating induction or concurrent chemotherapy (CT) with RT have been developed, with the aim of treating locally advanced LC patients while preserving the larynx and its functions. Overall, more than two-thirds of patients included in a LP program will not require total laryngectomy (TL) and will preserve a functional larynx. However, despite these advances, the larynx is the only tumor site in the upper aero-digestive tract for which prognosis has not improved during recent decades. Indeed, none of these LP protocols have shown any survival advantage compared to primary radical surgery, and it appears that certain LC patients do not benefit from an LP program. This is the case for patients with T4a LC (extra-laryngeal tumor extension through the thyroid cartilage) or with poor pretreatment laryngeal function and for whom primary TL is still the preferred therapeutic option. Moreover, TL is the standard salvage therapy for patients with recurrent tumor after an LP protocol.

Purpose of Review: The objective of this review article is to discuss the current role of surgery as the primary treatment modality in patients with head and neck squamous cell carcinoma (HNSCC)., Recent Findings: HNSCC represents one of the cancer locations where the primary treatment modality is the most under discussion. Indeed, the respective roles of primary surgical resection followed, as necessary, by adjuvant radiotherapy or definitive chemoradiotherapy remain controversial. The results of organ preservation trials and the drastic rise in the incidence of human papillomavirus-induced oropharyngeal tumors, which are known to be highly radiosensitive, have led to an increasing use of chemoradiation-based therapies in HNSCC patients. However, no chemoradiation-based protocol has shown better oncologic outcomes than radical primary surgery. Moreover, development of minimally invasive surgical techniques, such as transoral robotic surgery, and advances in head and neck microvascular reconstruction have considerably improved the clinical outcomes of the patients and have led to a reconsideration of the role of primary surgery in HNSCC patients., Summary: Surgery should be the primary treatment modality for most resectable oral cavity cancers and for T4a laryngeal/hypopharyngeal cancers. Primary surgery could also be the preferred modality of treatment for most early (T1-T2, N0) laryngeal and hypo/oropharyngeal carcinomas when this strategy offers an opportunity to reserve radiotherapy for a potential recurrence or second primary tumor. Primary surgery should also be considered in patients with locally advanced human papillomavirus-negative oropharyngeal carcinoma.

Introduction: Resections of cutaneous tumors in the medial orbitonasal region can be transfixing. Repairs using a single local flap run the risk of failure and that of secondary sinonasal fistula, especially in cases of surgery on a radiated field. We propose an original and reliable repair procedure using two pedicled regional flaps vascularized by two distinct arterial systems clinched together to reconstruct the mucosal and cutaneous planes., Materials and Methods: A first melolabial propeller flap (MPF) with a superior perforating pedicle was elevated and the cutaneous side was sutured to the deep plane of the loss of substance (mucosal lining). A second homolateral or contralateral paramedian forehead flap (PFF) was then lifted and sutured over the first flap (superficial plane). The forehead pedicle flap was divided at 1 month., Results: No trophic complication or failure was recorded on two patients. The 7-year carcinologic, aesthetic, and functional results were satisfying., Conclusion: This technique involving the superimposition of two local flaps, vascularized by two different arterial systems, appears to offer a simple and reliable repair technique for transfixing cutaneous losses of substance in the medial orbitonasal region. It could be used in the first-line treatment, particularly if an additional radiotherapy is to be performed.

Objectives: To analyze the impact of tumor p16 status and other clinical factors on the therapeutic decision-making process in patients with oropharyngeal squamous cell carcinoma (OPSCC)., Methods: We conducted a multicenter retrospective study (GETTEC collaborative study group) enrolling all OPSCC patients with a determined p16-status considered eligible for surgery between 2009 and 2014. The impact of p16-status and other clinical factors on the therapeutic decision was evaluated in multivariate analysis., Results: A total of 476 patients were enrolled in the study, including 244 cases (51%) of p16-positive OPSCC. Overall, 223 (47%) patients underwent primary surgery, and 184 (83%) of them received postoperative radiotherapy ± chemotherapy. More patients with p16-positive OPSCC tended to undergo non-surgical treatment than did patients with p16-negative OPSCC (p = 0.10). Multivariate analysis showed that 5 factors significantly influenced therapeutic management of the patients: T-stage ≥ 3 (towards a non-surgical strategy; p < 0.001), N-stage ≥ 2a (non-surgical strategy; p = 0.02), tumor involvement of the glosso-tonsillar sulcus (surgical strategy; p = 0.002), tumor extension to the oral cavity (surgical strategy; p < 0.009) and the center of care (p < 0.001). The rate of patients directed towards a surgical strategy varied between 9% and 74% depending on the center., Conclusion: There was a non-significant trend to recommend patients with p16-positive OPSCC for non-surgical treatment. Center of care, tumor stage and tumor anatomical subsite and extensions were the main determinants of the treatment choice., (Copyright © 2018 Elsevier Ltd, BASO ~ The Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved.)

Conclusion: Post-operative outcomes of salvage surgery for recurrent oropharyngeal squamous-cell carcinoma (OPSCC) were acceptable. Pathologic overall, T- or N-stage and patient comorbidities were the main predictors of patient clinical outcomes., Objectives: To evaluate post-operative outcomes of salvage surgery in patients with recurrent OPSCC and to determine their predictive factors., Materials and Methods: This study retrospectively reviewed the electronic medical records of all patients who underwent salvage surgery for recurrent OPSCC, between 2000-2013, in our institution. Overall survival (OS) and cause-specific survival (SS) were determined by Kaplan-Meier analysis. Predictive factors of post-operative outcomes were investigated by using univariate and multivariate analyses., Results: A total of 34 patients were included in this study. Local and general post-operative complication rates were 26% and 27%, respectively. A high level of comorbidity (Kaplan Feinstein Index: KFI ≥ 2) was the only factor associated with a higher risk of local (p = 0.03) and general (p = 0.04) complications. OS and SS rates at 3 years were 48% and 61%, respectively. In multivariate analysis, pathologic overall stage ≥ III was a significant predictor of OS (p = 0.02) and pathologic T-stage ≥ 3 was a significant predictor of SS (p = 0.01). Mean pre-operative and post-operative DOSS (dysphagia outcome and severity scale) scores were 4.4 and 3.9, respectively.