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Otolaryngologic Clinics of North America Dec 2020This article outlines the ways that transoral robotic surgery and transoral laser microsurgery relate to treatment de-escalation in the treatment of head and neck... (Review)
Review
This article outlines the ways that transoral robotic surgery and transoral laser microsurgery relate to treatment de-escalation in the treatment of head and neck cancer. Treatment de-escalation has particular importance in context of human papillomavirus-related oropharynx squamous cell carcinoma, which responds well to therapy but leaves many survivors with decades of treatment-related sequelae. We compare these less invasive transoral approaches with previously used open approaches to the oropharynx. We discuss the topic of treatment de-escalation in human papillomavirus-related disease and outline completed and ongoing clinical trials investigating the choice of primary treatment modality and de-escalation of adjuvant therapy.
Topics: Carcinoma, Squamous Cell; Humans; Laser Therapy; Microsurgery; Oropharyngeal Neoplasms; Papillomaviridae; Robotic Surgical Procedures
PubMed: 32917423
DOI: 10.1016/j.otc.2020.07.009 -
Oral Oncology Nov 2021Indocyanine green (ICG) fluorescence-based sentinel lymph node (SLN) biopsy has been promoted to detect early metastasis of oral/oropharyngeal carcinoma, but its... (Review)
Review
Indocyanine green (ICG) fluorescence-based sentinel lymph node (SLN) biopsy has been promoted to detect early metastasis of oral/oropharyngeal carcinoma, but its diagnostic value still remains unclear. In this letter, we identified 6 studies on ICG fluorescence based SLN in the detection of lymph node metastasis in oral/oropharyngeal carcinoma. For detection of metastatic lymph node, the overall sensitivity and specificity of the studies were 0.86 and 0.91, respectively. SROC curve was determined according to the combined sensitivity and specificity, and the overall area under the curve AUC was 0.93. On the whole, ICG fluorescence-based SLN biopsy showed promising effect for earlier detection and staging.
Topics: Carcinoma; Coloring Agents; Humans; Indocyanine Green; Lymph Nodes; Lymphatic Metastasis; Mouth Neoplasms; Neoplasm Staging; Oropharyngeal Neoplasms; Sentinel Lymph Node; Sentinel Lymph Node Biopsy
PubMed: 34656055
DOI: 10.1016/j.oraloncology.2021.105563 -
Head & Neck Feb 2021We aimed to compare unstimulated saliva flow using 3-minute modified Schirmer test (MST) following bilateral vs unilateral radiotherapy (RT) in oropharyngeal carcinoma... (Review)
Review
BACKGROUND
We aimed to compare unstimulated saliva flow using 3-minute modified Schirmer test (MST) following bilateral vs unilateral radiotherapy (RT) in oropharyngeal carcinoma (OPC).
METHODS
We reviewed OPC patients treated with definitive intensity-modulated radiation therapy (IMRT) between 2011 and 2017. MST was measured at baseline, 1-/6-/12-/24-month post-RT. MST values were compared between bilateral-RT vs unilateral-RT groups. Multivariable logistic regression analysis (MVA) identified predictors of hyposalivation (MST < 25 mm).
RESULTS
Total 498 bilateral-RT and 36 unilateral-RT patients were eligible. The MST values at 1-/6-/12-/24-month post-RT were all significantly reduced from baseline for the entire cohort. Baseline unilateral-RT and bilateral-RT MST values (in mm) were similar (P = .2), but much higher for unilateral-RT 1-month (mean: 19.1 vs 13.0, P = .03), 6-month (20.5 vs 9.3, P < .001), 12-month (20.1 vs 11.9, P < .01), and 24-month post-RT (22.2 vs 13.9, P = .04). MVA confirmed that unilateral RT reduced the likelihood of hyposalivation vs bilateral RT (OR 2.36, P = .006).
CONCLUSION
Unilateral RT reduces unstimulated salivary flow in OPC patients.
Topics: Carcinoma; Head and Neck Neoplasms; Humans; Oropharyngeal Neoplasms; Radiotherapy, Intensity-Modulated; Saliva; Xerostomia
PubMed: 33058305
DOI: 10.1002/hed.26496 -
Cell Reports. Medicine Nov 2023Tumor-infiltrating HPV16-E2-specific CD8 T cells have been detected in HPV16-induced oropharyngeal squamous cell carcinoma (OPSCC). Whether intratumoral CD4 T cells...
Tumor-infiltrating HPV16-E2-specific CD8 T cells have been detected in HPV16-induced oropharyngeal squamous cell carcinoma (OPSCC). Whether intratumoral CD4 T cells target HPV16 E2 and if HPV16-E2-specific immunity contributes to better clinical outcome is unknown. In a prospective HPV16 OPSCC cohort, we regularly detect HPV16-E2-specific CD4 and CD8 intratumoral T cells, albeit at lower frequencies than the co-infiltrating HPV16-E6/E7-specific T cells. These HPV16-reactive T cells produce multiple cytokines when activated, indicating their polyfunctionality. Importantly, their combined intratumoral presence predicts superior survival, emphasizing the value of HPV16-E2-specific T cells in anti-tumor immunity and suggests its use as a target antigen for immunotherapy.
Topics: Humans; Human papillomavirus 16; CD8-Positive T-Lymphocytes; Prospective Studies; Papillomavirus Infections; Oropharyngeal Neoplasms; Squamous Cell Carcinoma of Head and Neck; Head and Neck Neoplasms
PubMed: 37924817
DOI: 10.1016/j.xcrm.2023.101262 -
Pathology Dec 2021Tumour infiltrating lymphocytes (TILs) have been described as a biomarker for the host immune response against the tumour with prognostic properties. The International...
Tumour infiltrating lymphocytes (TILs) have been described as a biomarker for the host immune response against the tumour with prognostic properties. The International Immuno-Oncology Biomarkers Working Group (IBWG) proposed a standardised method for quantifying TILs in solid tumours to improve consistent and reproducible scoring. In this study, the methodology was tested in a retrospective population of oropharyngeal squamous cell carcinoma (OPSCC). TIL quantification was performed on 92 OPSCC samples (2004-2013) by four independent observers as described by the IBWG. Interobserver variability was assessed and results were correlated with clinicopathological variables and survival. TIL evaluation turned out to be challenging in OPSCC due to heterogeneity of TILs distribution, presence of pre-existing lymphoid tissue, surface ulceration or erosion and insufficient amount of intertumoural stroma in biopsies. Nonetheless, interobserver variability proved to be good to excellent. High stromal TILs (TILstr) and intratumoural TILs (TILtum) were both correlated to favourable overall survival and multivariate analysis showed TILstr to be the sole independent prognostic factor in OPSCC. The IBWG-proposed TIL quantification method is feasible and reproducible in OPSCC and provides valuable prognostic information regarding clinicopathological characteristics and overall survival. The use of this standardised methodology may facilitate implementation of TILs scoring as a prognostic biomarker in OPSCC.
Topics: Biomarkers, Tumor; Head and Neck Neoplasms; Humans; Lymphocytes, Tumor-Infiltrating; Oropharyngeal Neoplasms; Prognosis; Retrospective Studies; Squamous Cell Carcinoma of Head and Neck; Tumor Microenvironment
PubMed: 34217516
DOI: 10.1016/j.pathol.2021.03.005 -
European Journal of Cancer Care Nov 2021Squamous cell carcinoma in cervical lymph nodes arising from an undetected primary tumour, termed carcinoma of unknown primary (SCCUP), is a well-recognized clinical... (Review)
Review
Squamous cell carcinoma in cervical lymph nodes arising from an undetected primary tumour, termed carcinoma of unknown primary (SCCUP), is a well-recognized clinical presentation within head and neck oncology. SCCUP is a common presentation for patients with human papillomavirus-mediated oropharyngeal cancer (HPV + OPSCC), as patients with HPV + OPSCC often present with smaller primary tumours and early nodal metastasis. Meticulous work-up of the SCCUP patient is central to the management of these patients as identification of the primary site improves overall survival and allows for definitive oncologic resection or more focused radiation when indicated. This review summarizes the comprehensive diagnostic approach to the SCCUP patient, including history and physical examination, methods of biopsy of the cervical lymph node, imaging modalities and intraoperative methods to localize the unknown primary. Novel techniques such as transcervical ultrasound of the oropharynx, narrow band imaging and diagnostic transoral robotic surgery are also discussed.
Topics: Carcinoma, Squamous Cell; Head and Neck Neoplasms; Humans; Neck; Neoplasms, Unknown Primary; Oropharyngeal Neoplasms; Papillomaviridae; Papillomavirus Infections
PubMed: 33932056
DOI: 10.1111/ecc.13459 -
Otolaryngologia Polska = the Polish... Aug 2022To investigate the impact on local relapse rate (LRR) and disease specific survival (DSS) of intraoperative margins (FS) obtained by circumferential sampling method,...
OBJECTIVES
To investigate the impact on local relapse rate (LRR) and disease specific survival (DSS) of intraoperative margins (FS) obtained by circumferential sampling method, corresponding to the lesion shape and marked using clock-face orientation combined with narrow band imaging (NBI) in head and neck squamous cell carcinoma Materials and Methods: 147 consecutive patients who underwent primary surgery with radical intent for oral and oropharyngeal cancer between 2011 and 2016 were prospectively enrolled. Patients were assigned to 3 groups with different sampling methods. In group A (n=44) a classical FS sampling method was used. In group B (n=73), the clock-face orientation sampling method (FS oclock) was used, whereas in group C (n=30), the FS oclock method combined with NBI. The primary outcome measure was the interdependence between FS sampling methods and oncological outcomes measured by LRR and DSS.
RESULTS
In total, 1534 FS samples were obtained with range of 3-24 FS taken per case, median 7.25 in group A, 8.15 in group B and 7.52 in group C. When compared FS histology and final histology in all groups the sensitivity, specificity and accuracy were 61.54%, 98.51% and 95.24%, respectively. The overall LRR equaled 8.8%. The lowest LRR was observed in FS oclock method combined with NBI (6.67%) followed by FS oclock (6.85%) and FS classic (13.64%). For all patients, DSS achieved 95.92% - 95.45% in FS classic, 95.89% in FS oclock and 96.67%. in FS oclock combined with NBI.
CONCLUSION
The FS oclock sampling method combined with NBI increases the chance of achieving tumor-negative margins and in result improves the treatment outcome reflected by LRR and DSS.
Topics: Humans; Head and Neck Neoplasms; Narrow Band Imaging; Oropharyngeal Neoplasms; Margins of Excision
PubMed: 36805982
DOI: 10.5604/01.3001.0015.9678 -
Pathology, Research and Practice Aug 2022The MDM2 gene appears to be involved in the development of nasopharyngeal carcinoma. The aim of this study was to examine MDM2 expression in a series of nasopharyngeal...
BACKGROUND
The MDM2 gene appears to be involved in the development of nasopharyngeal carcinoma. The aim of this study was to examine MDM2 expression in a series of nasopharyngeal carcinoma biopsies to explore its potential diagnostic significance.
METHODS
The study cohort consisted of 26 nasopharyngeal carcinomas, including 22 EBV positive non-keratinizing squamous cell carcinomas (NKSCC), 1 EBV negative NKSCC and 3 EBV negative keratinizing SCC. For comparison, we selected 48 oropharyngeal carcinomas, including 17 HPV positive SCC (14 non-keratinizing and 3 keratinizing) and 31 HPV negative SCCs (28 keratinizing and 3 non-keratinizing). In addition, we examined MDM2 expression in a group of 26 cervical lymph node metastases, including 5 with EBV positive nasopharyngeal NKSCC and 21 from oropharyngeal carcinoma (18 non keratinizing HPV positive, 1 keratinizing HPV positive, 1 keratinizing HPV negative and 1 non-keratinizing HPV negative). Finally, 2 bone metastases from EBV positive nasopharyngeal NKSCC were also included. A tissue microarray was constructed from formalin-fixed paraffin embedded tumor tissue specimens. Sections were immunostained for MDM2 and in situ hybridization for EBER and CISH analysis for the MDM2 gene were also conducted in all cases.
RESULTS
Overall, MDM2 positivity was detected in 28 of 102 SCCs (27.2 %). MDM2 positivity was significantly more frequent in EBV positive NKSCC (80 %) than in oropharyngeal HPV positive NKSCC (6.1 %) and keratinizing SCCs (9.4 %) (p < 0.001, Pearson chi square). Considering only the primary tumors, 86.4 % of the nasopharyngeal carcinomas were positive, versus 13.5 % of the oropharyngeal carcinomas (p < 0.001, Pearson chi square). Considering the lymph node metastases, 3 of 5 EBV positive carcinomas with nasopharyngeal primary were positive, whereas only one of the HPV positive carcinomas was positive. Finally, both the bone metastases from EBV positive nasopharyngeal carcinoma were positive for MDM2. No amplification of the MDM2 gene was identified by in situ hybridization analysis.
CONCLUSIONS
Our data indicate that MDM2 could be a valuable diagnostic marker to support the diagnosis of nasopharyngeal EBV positive NKSCC.
Topics: Humans; Lymphatic Metastasis; Nasopharyngeal Carcinoma; Nasopharyngeal Neoplasms; Oropharyngeal Neoplasms; Papillomaviridae; Papillomavirus Infections; Proto-Oncogene Proteins c-mdm2; Squamous Cell Carcinoma of Head and Neck
PubMed: 35714490
DOI: 10.1016/j.prp.2022.153978 -
European Archives of... May 2021To perform a meta-analysis evaluating trans-oral robotic surgery (TORS), and intensity-modulated radiation therapy (IMRT) in the treatment of oropharyngeal squamous cell... (Meta-Analysis)
Meta-Analysis Review
PURPOSE
To perform a meta-analysis evaluating trans-oral robotic surgery (TORS), and intensity-modulated radiation therapy (IMRT) in the treatment of oropharyngeal squamous cell carcinoma (OPSCC).
METHODS
This study adhered to the PRISMA guidelines.
RESULTS
A total of 5624 patients (IMRT, n = 4322; TORS, n = 1302) were included in this meta-analysis. The majority of patients in the IMRT cohort were treated with concurrent CT (n = 3433, 81.3%). On the other hand, the majority of patients in the TORS cohort was treated with an adjuvant treatment (n = 826, 67.8%). IMRT subgroup showed a cumulative survival rate of 83.6% (99% CI 76.9-89.3%), while it was 91.3% (99% CI 81.2-97.8%) in the TORS subgroup. Disease-free survival was significantly different between IMRT (79.6%, 99% CI 70.6-87.3%), and TORS (89.4%, 99% CI 82.7-94.5%). IMRT subgroup showed a feeding tube dependence rate of 4.0% (99% CI 1.1-8.4%), but it was not significantly different from the TORS subgroup (1.3%, 99% CI 0-4.9%). Tracheostomy dependence rates were similar among the two subgroups (IMRT, 0.7%, 99% CI 0-1.1%; TORS, 0.2%, 99% CI 0-1.1%).
CONCLUSIONS
TORS appears to be a consolidated effective surgical approach in the management of OPSCC, according to both oncologic and functional outcomes. Further RCTs comparing TORS and IMRT with homogeneous cohorts in terms of tumor staging and HPV status are advisable.
Topics: Head and Neck Neoplasms; Humans; Oropharyngeal Neoplasms; Radiotherapy, Intensity-Modulated; Robotic Surgical Procedures; Squamous Cell Carcinoma of Head and Neck
PubMed: 32696250
DOI: 10.1007/s00405-020-06224-z -
Journal of Experimental & Clinical... Sep 2022Immune checkpoint inhibitors (ICI) are approved for treatment of recurrent or metastatic oropharyngeal head and neck squamous cell carcinoma in the first- and...
The immune microenvironment of HPV-positive and HPV-negative oropharyngeal squamous cell carcinoma: a multiparametric quantitative and spatial analysis unveils a rationale to target treatment-naïve tumors with immune checkpoint inhibitors.
BACKGROUND
Immune checkpoint inhibitors (ICI) are approved for treatment of recurrent or metastatic oropharyngeal head and neck squamous cell carcinoma in the first- and second-line settings. However, only 15-20% of patients benefit from this treatment, a feature increasingly ascribed to the peculiar characteristics of the tumor immune microenvironment (TIME).
METHODS
Immune-related gene expression profiling (GEP) and multiplex immunofluorescence (mIF) including spatial proximity analysis, were used to characterize the TIME of 39 treatment-naïve oropharyngeal squamous cell carcinomas (OPSCC) and the corresponding lymph node metastases. GEP and mIF results were correlated with disease-free survival (DFS). HPV-positive tumors disclosed a stronger activation of several immune signalling pathways, as well as a higher expression of genes related to total tumor-infiltrating lymphocytes, CD8 T cells, cytotoxic cells and exhausted CD8 cells, than HPV-negative patients. Accordingly, mIF revealed that HPV-positive lesions were heavily infiltrated as compared to HPV-negative counterparts, with a higher density of T cells and checkpoint molecules. CD8+ T cells appeared in closer proximity to tumor cells, CD163+ macrophages and FoxP3+ cells in HPV-positive primary tumors, and related metastases. In HPV-positive lesions, PD-L1 expression was increased as compared to HPV-negative samples, and PD-L1+ tumor cells and macrophages were closer to PD-1+ cytotoxic T lymphocytes. Considering the whole cohort, a positive correlation was observed between DFS and higher levels of activating immune signatures and T cell responses, higher density of PD-1+ T cells and their closer proximity to tumor cells or PD-L1+ macrophages. HPV-positive patients with higher infiltration of T cells and macrophages had a longer DFS, while CD163+ macrophages had a negative role in prognosis of HPV-negative patients.
CONCLUSIONS
Our results suggest that checkpoint expression may reflect an ongoing antitumor immune response. Thus, these observations provide the rationale for the incorporation of ICI in the loco-regional therapy strategies for patients with heavily infiltrated treatment-naïve OPSCC, and for the combination of ICI with tumor-specific T cell response inducers or TAM modulators for the "cold" OPSCC counterparts.
Topics: B7-H1 Antigen; Carcinoma, Squamous Cell; Forkhead Transcription Factors; Head and Neck Neoplasms; Humans; Immune Checkpoint Inhibitors; Oropharyngeal Neoplasms; Papillomavirus Infections; Programmed Cell Death 1 Receptor; Spatial Analysis; Squamous Cell Carcinoma of Head and Neck; Tumor Microenvironment
PubMed: 36123711
DOI: 10.1186/s13046-022-02481-4