The prognostic-nutritional index in HPV-negative head and neck squamous cell carcinoma treated with upfront surgery: a multi-institutional series

Objectives: To evaluate the prognostic value of pre-treatment prognostic-nutritional index (PNI) in patients with HPV-negative head and neck squamous cell carcinoma (HNSCC). Methods: A multi-institutional retrospective series of HPV-negative, Stages II-IVB, HNSCCs treated with upfront surgery was evaluated. Correlation of pre-operative blood markers and PNI with 5-year overall (OS) and relapse-free (RFS) survival was tested using linear and restricted cubic spline models, as appropriate. The independent prognostic effect of patient-related features was assessed with multivariable models. Results: The analysis was conducted on 542 patients. PNI ≥ 49.6 (HR = 0.52; 95% CI, 0.37-0.74) and Neutrophil-to-Lymphocyte Ratio (NLR) > 4.2 (HR = 1.58; 95% CI, 1.06-2.35) confirmed to be independent prognosticators of OS, whereas only PNI ≥ 49.6 (HR = 0.44; 95% CI, 0.29-0.66) was independently associated with RFS. Among pre-operative blood parameters, only higher values of albuninaemia and lymphocyte count (> 1.08 x 103/microL), and undetectable basophile count (= 0 103/microL) were independently associated with better OS and RFS. Conclusions: PNI represents a reliable prognostic tool providing an independent measure of pre-operative immuno-metabolic performance. Its validity is supported by the independent prognostic role of albuminaemia and lymphocyte count, from which it is derived

Advanced lung cancer inflammation index and its prognostic value in HPV-negative head and neck squamous cell carcinoma: a multicentre study

Purpose: The aim of this study is to evaluate the prognostic value of pre-treatment advanced lung cancer inflammation index (ALI) in patients with HPV-negative HNSCC undergoing up-front surgical treatment. Methods: The present multi-centre, retrospective study was performed in a consecutive cohort of patients who underwent upfront surgery with or without adjuvant (chemo)-radiotherapy for head and neck squamous cell carcinoma (HNSCC). Patients were stratified by ALI, and survival outcomes were compared between groups. In addition, the prognostic value of ALI was compared with two other indices, the prognostic nutritional index (PNI) and systemic inflammatory index (SIM). Results: Two hundred twenty-three patients met the inclusion criteria (151 male and 72 female). Overall and progression-free survival were significantly predicted by ALI < 20.4 (HR 3.23, CI 1.51–6.90 for PFS and HR 3.41, CI 1.47–7.91 for OS). Similarly, PNI < 40.5 (HR = 2.43, 95% CI: 1.31–4.51 for PFS and HR = 2.40, 95% CI: 1.19–4.82 for OS) and SIM > 2.5 (HR = 2.51, 95% CI: 1.23–5.10 for PFS and HR = 2.60, 95% CI: 1.19–5.67 for OS) were found to be significant predictors. Among the three indices, ALI < 20.4 identified the patients with the worst 5-year outcomes. Moreover, patients with a combination of low PNI and low ALI resulted to be a better predictor of progression (HR = 5.26, 95% CI: 2.01–13.73) and death (HR = 5.68, 95% CI: 1.92–16.79) than low ALI and low PNI considered alone. Conclusions: Our results support the use of pre-treatment ALI, an easily measurable inflammatory/nutritional index, in daily clinical practice to improve prognostic stratification in surgically treated HPV-negative HNSCC

Prognostic value of H-index in patients surgically treated for squamous cell carcinoma of the larynx.

OBJECTIVE: Recently, a novel host-related index, the Host-index (H-index), including both inflammatory and nutritional markers, has been described and observed to stratify prognosis in patients with squamous cell carcinoma (SCC) of the oral cavity more accurately than other host-related indexes This study aimed to investigate the prognostic performance of the H-index using pretreatment blood tests in patients receiving up-front surgery for SCC of the larynx. METHODS: This retrospective observational study included a multicenter series of consecutive patients with SCC of the larynx diagnosed between 1 January 2009 and 31 July 2018, whose pretreatment blood tests were available and included the parameters necessary for the calculation of neutrophil to lymphocyte ratio (NLR) and the H-index. Their association with disease-free survival (DFS) and overall survival (OS) was measured. RESULTS: A total of 231 patients were eligible for the present analysis (median [range] age, 68 [37-96] years; 191 [82.7%] men). The median follow-up was 73 months. In multivariable Cox proportional hazards regression models, increasing age (adjusted hazard ratio [aHR], 1.07 per year; 95% CI, 1.04-1.09), advanced pT stage (aHR = 1.71 95% CI: 1.07-2.71), and having close or positive surgical margins (aHR = 2.01; 95% CI: 1.21-3.33) were significantly associated with poor OS. Among blood parameters, a higher neutrophil count was a strong predictor of both worse DFS (aHR for recurrence/death = 2.34; 95% CI: 1.24-4.40) and OS (aHR for death = 2.67; 95% CI: 1.51-4.71). Among inflammatory blood indexes, while NLR was not significantly associated with DFS or OS, patients with H-index ≥8.37 showed a higher aHR for both recurrence/death (2.82; 95% CI: 1.65-4.79) and death (2.22; 95% CI: 1.26-3.89). CONCLUSION: In conclusion, the present study confirms the prognostic value of pretreatment H-index, an easily measurable inflammatory and nutritional index, in patients with SCC of the larynx. LEVEL OF EVIDENCE: III

Oncological and functional results by horizontal glottectomy in laryngeal carcinomas

BACKGROUND: The aim of this study is to describe the indications, surgical technique and results of horizontal glottectomy in laryngeal carcinomas. MATERIALS AND METHODS: Twenty patients suffering from differentiated glottal carcinoma (15 T1b and 5 T1a) were treated between 1985 and 1994. A classic horizontal glottectomy, with some modifications, not extended to the ventricular fold or to the arytenoid, was performed in every patient. All patients followed a postoperative rehabilitative program. Time of feeding tube removal, decannulation and voice production were considered. RESULTS: No local recurrence was recorded in any of the patients, however follow up on 4 cases was only three years. No postoperative radiotherapy was used. Two patients died from cardiovascular causes. Post-operative average times were: discharge from hospital after 10.5 days; feeding tube removal after 7 days; decannulation after 9.5 days. No major pulmonary complications nor laryngeal stenosis following surgery was recorded. In all patients adequate voice production was achieved. CONCLUSIONS: Our results show that horizontal glottectomy is a safe procedure in the treatment of laryngeal cancer. Local control of disease, provided case selection is very accurate, can reach 100%. Rapid and excellent laryngeal function may thus be obtained and the voice production is adequate in every patient

Surgical Treatment of Tracheostomal Stenosis

Stenosis of the tracheostome is a frequent complication following total laryngectomy; the problems created by tracheostomal stenosis are the result of reduced airflow and consequent turbulence. Many authors have studied etiological factors for the onset of stomal stenosis, and a number of procedures have been recommended for the surgical correction of such stenosis. Study Design: A prospective analysis of 12 patients who underwent surgical correction of stomal stenosis is presented. Methods: At the Institute of Clinical Otolaryngology we have recently defined a surgical technique for the correction of stomal stenosis that combines radial incisions, V-shaped flaps, and interposing flaps. This technique enables us to correct all the types of stenosis, and we have treated 12 patients to date. Results: To date, the average follow-up has been 17 months (range, 3\u201336 mo), and the results are encouraging. Early stenosis of the tracheostoma reappeared in one patient, who had successful repeat surgery with the same technique. Conclusions: Early results suggest the routine use of this surgical technique in the treatment of stomal stenosis

Prognostic significance of LINE-1 hypomethylation in oropharyngeal squamous cell carcinoma

Inclusion of new biomarkers to improve a personalized treatment approach for oropharyngeal squamous cell carcinoma (OPSCC) is urgently needed. Hypomethylation of the Long interspersed nucleotide element-1 (LINE-1) repetitive elements, a widely accepted surrogate of overall genomic DNA methylation content, was found to be associated with a poor prognosis in several cancers. At present, no studies have investigated the influence of LINE-1 methylation levels on OPSCC relapse. The main goal of this study was the evaluation of the prognostic value of LINE-1 methylation status in predicting early tumor relapse in locally advanced OPSCC

HPV-related Oropharyngeal Squamous Cell Carcinoma: p16INK4A Immunohistochemistry or HPV Genotyping?

Infection with high-risk human papillomavirus (HPV) is linked to a sub-group of squamous cell oropharyngeal tumors (OPSCC). Our aim was to compare an HPV Polymerase Chain Reaction (PCR) assay and p16(INK4A) expression status by immunohistochemistry (IHC) as a surrogate marker

Rising Trend in the Prevalence of HPV-Driven Oropharyngeal Squamous Cell Carcinoma during 2000–2022 in Northeastern Italy: Implication for Using p16^INK4a as a Surrogate Marker for HPV-Driven Carcinogenesis

Background: The prevalence and incidence of oropharyngeal squamous cell carcinomas (OPSCCs) driven by human papillomavirus (HPV) infection are increasing worldwide, being higher in high-income countries. However, data from Italy are scanty. p16INK4a overexpression is the standard in determining HPV-driven carcinogenesis, but disease prevalence impacts on its positive predictive value. Methods: This is a multicenter retrospective study enrolling 390 consecutive patients aged ≥18 years, diagnosed with pathologically confirmed OPSCC in Northeastern Italy between 2000 and 2022. High-risk HPV-DNA and p16INK4a status were retrieved from medical records or evaluated in formalin-fixed paraffin-embedded specimens. A tumor was defined as HPV-driven when double positive for high-risk HPV-DNA and p16INK4a overexpression. Results: Overall, 125 cases (32%) were HPV-driven, with a significant upward temporal trend from 12% in 2000–2006 to 50% in 2019–2022. The prevalence of HPV-driven cancer of the tonsil and base of the tongue increased up to 59%, whereas it remained below 10% in other subsites. Consequently, the p16INK4a positive predictive value was 89% for the former and 29% for the latter. Conclusions: The prevalence of HPV-driven OPSCC continued to increase, even in the most recent period. When using p16INK4a overexpression as a surrogate marker of transforming HPV infection, each institution should consider the subsite-specific prevalence rates of HPV-driven OPSCC as these significantly impact on its positive predictive value

Blood Markers Predicting Clinically Occult Lymph Node Metastasis in Head and Neck Squamous Cell Carcinoma

Introduction: The presence of cervical lymph node metastases is an unfavorable prognostic factor in head and neck squamous cell carcinoma (HNSCC) and a potential cause of treatment failure. Occult lymph node metastasis occurs in approximately 15-20% of HNSCC patients with a clinically negative neck (cN0), greatly impacting on their prognosis. The present study aimed to investigate the role of pre-treatment peripheral blood markers in predicting clinically occult cervical lymph node metastasis. Methods: This multicenter, retrospective study was performed in a cohort of 472 patients diagnosed with cN0 HNSCC who underwent up-front surgery. Baseline neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), lymphocyte-to-monocyte ratio (LMR), systemic inflammatory marker (SIM), and systemic immune-inflammation index (SII) were calculated from available blood parameters. Results: Oro-hypopharyngeal and oral cancers, locally advanced stage, moderately (G2), and poorly (G3) differentiated grade were associated with an increased risk of pathological lymph node involvement. NLR, LMR, PLR, SIM, and SII were significantly associated at multivariable analysis. NLR >2.12 was the most reliable at predicting occult lymph node metastasis (OR = 5.22; 95% CI: 2.14-12.75). We describe a predictive score integrating cancer site, local stage, and NLR which is effective at predicting positive lymph node pathological status. Conclusions: The present study provides evidence that pre-treatment peripheral blood markers, in particular NLR, represent reliable predictors of clinically occult cervical lymph node metastasis in cN0 HNSCC. Therefore, the present study provides a novel useful predictive score for directing the elective management of the neck in patients with cN0 HNSCC