The landscape of circulating tumor HPV DNA and TTMV-HPVDNA for surveillance of HPV-oropharyngeal carcinoma: systematic review and meta-analysis.

BACKGROUND: Human papilloma virus (HPV) related cancers of the oropharynx are rapidly increasing in incidence and may soon represent the majority of all head and neck cancers. Improved monitoring and surveillance methods are thus an urgent need in public health. MAIN TEXT: The goal is to highlight the current potential and limitations of liquid biopsy through a meta analytic study on ctHPVDNA and TTMV-HPVDNA. It was performed a Literature search on articles published until December 2023 using three different databases: MEDLINE, Embase, and Cochrane Library. Studies that evaluated post-treatment ctHPVDNA and TTMV-HPVDNA in patients with HPV + OPSCC, studies reporting complete data on the diagnostic accuracy in recurrence, or in which the number of true positives, false positives, true negatives, and false negatives was extractable, and methods of detection of viral DNA clearly defined. The meta-analysis was conducted following the Meta-analysis Of Observational Studies in Epidemiology (MOOSE) reporting guidelines. The aim of this meta-analysis was to evaluate the sensitivity, specificity, and accuracy of ctHPVDNA and TTMV by ddPCR to define its efficacy in clinical setting for the follow up of HPV-OPSCC. CONCLUSION: The 12 studies included in the meta-analysis provided a total of 1311 patients for the analysis (398 valuated with ctHPVDNA and 913 with TTMV-HPVDNA). Pooled sensitivity and specificity were 86% (95% CI: 78%-91%) and 96% (95% CI: 91%-99%), respectively; negative and positive likelihood ratios were 0.072 (95% CI: 0.057-0.093) and 24.7 (95% CI: 6.5-93.2), respectively; pooled DOR was 371.66 (95% CI: 179.1-918). The area under the curve (AUC) was 0.81 (95% CI, 0.67-0.91). Liquid biopsy for the identification of cell free DNA might identify earlier recurrence in HPV + OPSCC patients. At the present time, liquid biopsy protocol needs to be standardized and liquid biopsy cannot yet be used in clinical setting. In the future, a multidimensional integrated approach which links multiple clinical, radiological, and laboratory data will contribute to obtain the best follow-up strategies for the follow-up of HPV-OPSCC.

Circulating tumor HPV DNA in the management of HPV+ oropharyngeal cancer and its correlation with MRI.

BACKGROUND: First aim was to compare ddPCR assays of ctHPVDNA with p16 IHC and qualitative HPV PCR. Second aim was to carry out longitudinal blood sampling to test for association of ctHPVDNA with histological confirmed recurrence. Third aim was to perform a multidimensional assessment which included: (1) clinical features; (2) ctHPVDNA; (3) MRI-based tumor size measurements of primary tumor (PT) and cervical lymph node metastases (CLNM). METHODS: Plasma samples were collected before treatment and during follow-up, and ddPCR assay comprising E6 of HPV16 and HPV 33 and HPV 35 was used. RESULTS: Present study was conducted at diagnosis in 117 patients and revealed a ctHPVDNA sensitivity of 100% (95% CI 95.5-100) and a specificity of 94.4 (95% CI 81.3-99.3), positive predictive value (PPV) of 94.4 (95% CI 81.3-99.3), and negative predictive value (NPP) of 100% (95% CI 89.7-100). During follow-up ctHPVDNA had a sensitivity of 100% (95% CI 72.1-100)% and specificity of 98.4% (95% CI 91.7-100)%, PPV% of 90.9% (95% CI 62.3-98.4) and NPV% of 100% (95% CI 94.3-100) for ability to detect recurrence. Correlation between both the CLNM volume and the sum of PT and CLNM volume was observed. CONCLUSIONS: ctHPVDNA was superior to p16 in identification of HPV-OPSCC at diagnosis. Introduction of ctHPVDNA, beyond diagnostic setting, represents a great opportunity to improve follow-up protocol of OPSCC patients.

Impact of Adjuvant Radiotherapy in Squamous Cell Carcinoma of the Oral Cavity with Perineural Invasion.

OBJECTIVE: Current guidelines indicate postoperative radiotherapy (PORT) in oral squamous cell carcinoma (OSCC) with perineural invasion (PNI), however, its real benefit has never been proven. The aim of our study is to investigate the benefit of PORT in OSCC patients with PNI in terms of survival and disease control. DATA SOURCES: The Pubmed/MEDLINE, Cochrane Library, and Scopus databases. REVIEW METHODS: Patients with PNI + OSCC treated with primary surgery were extracted from the included studies. The pooled logHR was calculated by comparing patients who underwent PORT to those who underwent only observation for overall survival (OS), disease-specific survival (DSS), disease-free survival (DFS), and locoregional control (LRC). RESULTS: About 690 patients with primary OSCC and PNI were included from nine studies. 374 (54.2%) patients underwent PORT, while 316 (45.8%) underwent observation. Analyses showed non-significant difference between the two groups for OS (HR: 1.01; 95% CI: 0.38-2.69), DSS (HR: 2.03; 95% CI: 0.54-7.56), and LRC (HR: 0.89; 95% CI: 0.53-1.50). They showed a significant difference in terms of DFS (HR: 0.86; 95% CI: 0.77-0.97). CONCLUSION: The real benefit of PORT in OSCC patients with PNI is still unclear, although it may have a positive impact on DFS. Clinicians should consider individual patient's characteristics, tumor factors, and treatment goals when deciding whether to recommend PORT. Further studies are needed to clarify which entity of PNI really benefits from PORT. LEVEL OF EVIDENCE: NA Laryngoscope, 134:2019-2027, 2024.

It is time to improve the diagnostic workup of oropharyngeal cancer with circulating tumor HPV DNA: Systematic review and meta-analysis.

The possibility of detecting circulating tumor HPV DNA (ctHPVDNA) in plasma in patients with oropharyngeal cancer has been demonstrated in several reports. However, these data are from small cohorts and available tests for detection of ctHPVDNA are not fully validated. The aim is to evaluate sensitivity, specificity, and accuracy of ctHPVDNA by ddPCR to define its efficacy in the clinical setting for the diagnosis of HPV + OPSCC. A comprehensive search of three different databases: MEDLINE, Embase, and Cochrane Library databases. A total of 998 patients were evaluated from the 13 studies. OPSSC p16+ were 729, while controls p16- were 269. The meta-analytic study estimated the diagnostic performance of ctHPVDNA as follows: pooled sensitivity and specificity of 0.90 (95% CI: 0.82-0.94) and 0.94 (95% CI: 0.85-0.98), respectively; positive and negative likelihood ratios of 12.6 (95% CI: 4.9-32.1) and 0.05 (95% CI: 0.02-0.13), respectively. ddPCR for ctHPVDNA has good accuracy, sensitivity, and specificity for diagnosis of HPV + OPSCC. ctHPVDNA kinetic represents a great reliable opportunity to improve diagnostic and therapeutic management of cancer patients and could open new perspectives for understanding tumor biology.

Second primary carcinoma arising on a flap: a new primary or a relapse?

BACKGROUND AND AIM: Free flaps or pedicle flaps are the mainstay of cancer surgery in the head and neck area. However, their long-term sequelae are still poorly understood. Among these, the development of a secondary primary tumor on a flap is a rare and uncertain reported event.   Methods: A computer-aided systematic literature search was performed by using the PubMed, EMBASE and Cochrane Library databases. A systematic review of the literature, following the PRISMA checklist, was carried out with the aim of analyzing all the citations reporting this second primary, with attention to risk factors, behavior, etiological causes.   Results: Overall, 27 cases of second primary squamous cell carcinoma arising on a pedicle or free flap were identified. In addition, other three cases were discussed.   Conclusions: Persistent exposure to oral stimuli such saliva, oral microbiome, smoke or a colonization by the adjacent mucosa were considered as a possible cause of second primary carcinoma. Although rare, a new neoplasm onset should know and considered as a new concept in the follow-up of patients undergoing reconstruction with free or pedicle flaps.

Trans oral robotic surgery for oropharyngeal cancer: A multi institutional experience.

OBJECTIVES: Trans Oral Robotic Surgery (TORS) has proved to be a safe and feasible treatment for oropharyngeal squamous cell carcinoma (OPSCC). The aim of this study is to analyse oncological outcomes of OPSCC patients treated with TORS. MATERIALS AND METHODS: This study involved 139 patients with OPSCC, treated with TORS between 2008 and 2020. Clinicopathological characteristics, treatment details and oncological outcomes were evaluated retrospectively. RESULTS: The management strategies included TORS alone in 42.5%, TORS-RT in 25.2% and TORS-CRT in 30.9%. The ENE was noted in 28.8% of neck dissections. In 19 patients clinically classified as unknown primaries, the primary was found in 73.7%. Rates of local, regional relapses and distant metastasis were 8.6%, 7.2%, and 6.5%, respectively. The 5 year- Overall Survival and Disease Free Survival were 69.6% and 71.3%, respectively. CONCLUSION: TORS fits well in the modern management of OPSCC. Although definitive CRT remains a milestone, TORS is proving to be a valid and safe treatment option. The choice of the therapeutic strategy requires evaluation by a multidisciplinary team.

Machine learning in laryngeal cancer: A pilot study to predict oncological outcomes and the role of adverse features.

BACKGROUND: Laryngeal carcinoma (LC) remains a significant economic and emotional problem to the healthcare system and severe social morbidity. New tools as Machine Learning could allow clinicians to develop accurate and reproducible treatments. METHODS: This study aims to evaluate the performance of a ML-algorithm in predicting 1- and 3-year overall survival (OS) in a cohort of patients surgical treated for LC. Moreover, the impact of different adverse features on prognosis will be investigated. Data was collected on oncological FU of 132 patients. A retrospective review was performed to create a dataset of 23 variables for each patient. RESULTS: The decision-tree algorithm is highly effective in predicting the prognosis, with a 95% accuracy in predicting the 1-year survival and 82.5% in 3-year survival; The measured AUC area is 0.886 at 1-year Test and 0.871 at 3-years Test. The measured AUC area is 0.917 at 1-year Training set and 0.964 at 3-years Training set. Factors that affected 1yOS are: LNR, type of surgery, and subsite. The most significant variables at 3yOS are: number of metastasis, perineural invasion and Grading. CONCLUSIONS: The integration of ML in medical practices could revolutionize our approach on cancer pathology.

Transoral Laser Microsurgery in Recurrent Laryngeal Cancer: A Systematic Review and Meta-analysis.

OBJECTIVE: To determine the oncological outcomes of salvage transoral laser microsurgery (TLM) in the treatment of patients suffering from recurrent laryngeal cancer. METHODS: PubMed/MEDLINE, Cochrane Library, and Scopus databases were searched. English language, original studies investigating oncological outcomes of TLM in adult patients with recurrent laryngeal cancer were included. Data were pooled using a distribution-free approach for estimating summary local control (LC), disease-specific survival (DSS), and overall survival (OS) curves with random effects. RESULTS: Two hundred and thirty-five patients underwent salvage TLM after primary (chemo)radiotherapy. The mean follow-up time was 60.8 months (95% CI: 32.7-88.9). Estimated pooled LC rates (95% CI) at 1, 3 and 5 years were 74.2% (61.7-89.4), 53.9% (38.5-75.3), and 39.1% (25.2-60.8). Estimated pooled DSS rates (95% CI) at 1, 3 and 5 years were 88.4% (82.0-95.3), 67.8% (50.9-90.3), and 58.9% (42.7-81.1). Two hundred and seventy-one patients underwent TLM after primary laser treatment. The mean follow-up time was 70.9 months (95% CI: 36.9-104.9). Estimated pooled LC rates (95% CI) at 1, 3 and 5 years were 72.2% (64.7-80.6), 53.2% (42.2-66.9), and 40.4% (29.6-55.2). Estimated pooled DSS rates (95% CI) at 1, 3 and 5 years were 92.1% (85.5-99.1), 77.0% (64.4-92.0), and 67.1% (51.6-87.3). CONCLUSIONS: TLM is a valuable treatment option for the management of locally recurrent laryngeal carcinoma if performed by experienced surgeons and following rigorous patients' selection criteria. Further studies should be conducted to define stage-based clinical guidelines. LEVEL OF EVIDENCE: NA Laryngoscope, 133:1425-1433, 2023.

Treatment of oropharyngeal squamous cell carcinoma: Is swallowing quality better after TORS or RT?

BACKGROUND AND PURPOSE: To answer an important question regarding the long-term morbidity of two oncological equivalent treatment for oropharyngeal squamous cell carcinoma (OPSCC), namely a comparison of swallowing function results between patients treated with trans-oral robotic surgery (TORS) versus patients treated with radiotherapy (RT). MATERIALS AND METHODS: Studies included patients with OPSCC treated with TORS or RT. Articles reporting complete data on MD Anderson Dysphagia Inventory (MDADI) and comparing the two treatments (TORS vs RT) were included in the meta-analysis. Swallowing assessed with MDADI was the primary outcome, the evaluation with instrumental methods was the secondary aim. RESULTS: Included studies provided a total of 196 OPSCC primarily treated with TORS vs 283 OPSCC primarily treated with RT. The mean difference in MDADI score at the longest follow-up was not significantly different between TORS and RT group (mean difference [MD] -0.52; 95% CI -4.53-3.48; p = 0.80). After treatment, mean composite MDADI scores demonstrated a slight impairment in both groups without reaching a statistical difference compared to the baseline status. DIGEST score and Yale score showed a significantly worse function in both treatment groups at 12-month follow-up compared to baseline status. CONCLUSION: The meta-analysis demonstrates that up-front TORS (+- adjuvant therapy) and up-front RT (+- CT) appear to be equivalent treatments in functional outcomes in T1-T2, N0-2 OPSCC, however, both treatments cause impaired swallowing ability. Clinicians should have a holistic approach and work with patients to develop an individualized nutrition plan and swallowing rehabilitation protocol from diagnosis to post-treatment surveillance.

Partial laryngectomy for naïve pT3N0 laryngeal cancer: Systematic review on oncological outcomes.

The first aim was to define the oncologic outcomes of open partial laryngectomy (OPL) in naïve pT3 laryngeal cancer. The second aim was to analyze the outcomes after OPL versus total laryngectomy (TL). A literature search was conducted in three databases (MEDLINE, EMBASE, and Cochrane Library) until January 2022. In 805 patients treated with OPL, 5-year OS, DSS, DFS and LFS were 80.5% (95% CI 70.6-87.6), 83.4% (95% CI 75.7-89), 77.4% (95% CI 66.3-85.7) and 77.9% (95% CI 68.7-85), respectively. Three articles compared TL versus OLP: 5-year OS, DSS and DFS risk difference were 0.100 (95% CI -0.092 to 0.291), 0.067 (95% CI -0.085 to 0.220) and 0.018 (95% CI -0.164 to 0.201) respectively. OPL for selected pT3 laryngeal cancer is able to guarantee a high percentage of oncological success. Accurate patient selection is of utmost importance to differentiate advanced disease amenable to conservative surgery.

Dynamics of humoral and cellular response to three doses of anti-SARS-CoV-2 BNT162b2 vaccine in patients with hematological malignancies and older subjects.

Background: Few data are available about the durability of the response, the induction of neutralizing antibodies, and the cellular response upon the third dose of the anti-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine in hemato-oncological patients. Objective: To investigate the antibody and cellular response to the BNT162b2 vaccine in patients with hematological malignancy. Methods: We measured SARS-CoV-2 anti-spike antibodies, anti-Omicron neutralizing antibodies, and T-cell responses 1 month after the third dose of vaccine in 93 fragile patients with hematological malignancy (FHM), 51 fragile not oncological subjects (FNO) aged 80-92, and 47 employees of the hospital (healthcare workers, (HW), aged 23-66 years. Blood samples were collected at day 0 (T0), 21 (T1), 35 (T2), 84 (T3), 168 (T4), 351 (T pre-3D), and 381 (T post-3D) after the first dose of vaccine. Serum IgG antibodies against S1/S2 antigens of SARS-CoV-2 spike protein were measured at every time point. Neutralizing antibodies were measured at T2, T3 (anti-Alpha), T4 (anti-Delta), and T post-3D (anti-Omicron). T cell response was assessed at T post-3D. Results: An increase in anti-S1/S2 antigen antibodies compared to T0 was observed in the three groups at T post-3D. After the third vaccine dose, the median antibody level of FHM subjects was higher than after the second dose and above the putative protection threshold, although lower than in the other groups. The neutralizing activity of antibodies against the Omicron variant of the virus was tested at T2 and T post-3D. 42.3% of FHM, 80,0% of FNO, and 90,0% of HW had anti-Omicron neutralizing antibodies at T post-3D. To get more insight into the breadth of antibody responses, we analyzed neutralizing capacity against BA.4/BA.5, BF.7, BQ.1, XBB.1.5 since also for the Omicron variants, different mutations have been reported especially for the spike protein. The memory T-cell response was lower in FHM than in FNO and HW cohorts. Data on breakthrough infections and deaths suggested that the positivity threshold of the test is protective after the third dose of the vaccine in all cohorts. Conclusion: FHM have a relevant response to the BNT162b2 vaccine, with increasing antibody levels after the third dose coupled with, although low, a T-cell response. FHM need repeated vaccine doses to attain a protective immunological response.

The T-shaped FST pharyngoplasty step-by-step closure technique.

Pharyngocutaneous fistula is one of the most common and serious complications associated with total laryngectomy. Numerous studies tried to evaluate causative and predisposing factors associated with this complication, but data are considerably variable and there is still no international consensus. Incidence rate varies considerably between studies, with reported rates from 3% to 65%. This 4K video presents our T-shaped four-step technique (FST) for closing the pharyngeal mucosa after total laryngectomy in a step-by-step manner. All sutures were performed by braided absorbable 3/0 26 mm 1/2c (Vicryl plus 3.0; Ethicon, Somerville, NJ, USA). Recordings were performed using a Karl Storz 4K 3D VITOM® exoscope (Karl Storz SE & Co. KG, Tuttlingen, Germany). We have been described this technique through a high-definition video, showing each step, and tips from the authors. Our T-shaped pharyngoplasty closure technique can be divided into four steps: 1. "Key Stitches"; 2. "Area Refinement Stitches"; 3. "Modified Connell Suture"; 4. "Modified Purse String Suture." Our T-shaped FST closure technique proved to be an effective and reproducible method, which we feel could be the preferred choice for primary pharyngoplasty closure.

Occult Neck Metastases in Head and Neck Adenoid Cystic Carcinoma: A Systematic Review and Meta-Analysis.

Introduction: Adenoid cystic carcinoma (AdCC) is a rare tumor whose clinical course is burdened by local recurrence and distant dissemination. Lymph node metastasis is not believed to be common and its clinical impact is controversial. The aim of this study was to determine: (1) the prevalence of occult metastasis at diagnosis in cN0 head and neck AdCC, (2) its prognostic role, and (3) the consequent need to perform elective neck dissection (END). Material and Methods: A systematic review and meta-analyses following PRISMA guidelines was performed. PubMed, Embase, and Central databases were questioned up to July 2021 to identify studies reporting on the prevalence of occult neck metastases in head and neck AdCC. A single-arm meta-analysis was then performed to determine the pooled prevalence of occult lymph node metastases among the retained studies. Results: Of the initial 6317 studies identified, 16 fulfilled the inclusion criteria, and they were included in the meta-analysis. Of a population of 7534 patients, 2530 cN0 patients were treated with END, which revealed 290/2530 cases of occult metastases (pN+/cN0). Meta-analysis of the results of END in the 16 studies estimated an overall prevalence of occult metastases at diagnosis of 17%. No further subgroup analysis was possible to identify factors influencing lymph node involvement and the prognostic role of END. Conclusions: Taking 20% as an historically proposed cut off, a 17% prevalence of occult metastases represents a borderline percentage to get a definitive conclusion about the indication to END for head and neck AdCC. A more advanced UICC stage, an oropharyngeal minor salivary glands origin, and a high-grade transformation are factors to be considered in a comprehensive patient's tailored therapeutic strategy. Multicenter prospective studies are the key to finding stronger recommendations on this topic.

Rapid decline of humoral response to two doses of BNT162b2 vaccine in patients with solid cancer after six months: The urgent need of the additional dose!

INTRODUCTION: We previously reported on the immunogenicity and safety of BNT162b2 in a large cohort of patients with cancer after the first and second doses (Di Noia et al., 2021) [1]. Herein, we present result after six months of follow-up. METHODS: This prospective study included patients affected by solid tumors and afferent to our institution who received two doses of BNT162b2 vaccine. A cohort of vaccinated healthcare workers (HCW) was used as control-group. Both cohorts were evaluated for the titer of anti-Spike (S) IgG at prefixed time-points (TPs). Time-point 4 was scheduled at 24-26 weeks after the second dose. RESULTS: In the current analysis, 400 patients and 232 healthcare workers were evaluated. Responders (IgG > 15 AU/mL) in patients group were 86.5% compared with 94.4% among healthcare workers. Also the IgG titer at TP4 was significantly inferior in patients than in healthcare workers (70.81 vs 134.64 AU/ml, p < 0.001). There was a more rapid decline of the antibody level from TP3 to TP4 in patients than in healthcare workers (1.78 vs 1.3 fold). The estimated IgG half-life was significantly shorter for patients (73 days) than in healthcare workers (118 days) as well as the time to reach negative serological status (340 vs 532 days). CONCLUSION: The decline of humoral response to the vaccine observed in patients with solid cancer after six months from the first dose support the urgent need of an early additional dose.

Open partial horizontal laryngectomy for T2-T3-T4a laryngeal cancer: oncological outcomes and prognostic factors of two Italian hospitals.

PURPOSE: The purpose of this study was to analyse the oncologic results of open partial horizontal laryngectomy (OPHL) and to assess the prognostic factors that could affect the survival of patients affected by T2, T3 and T4a laryngeal cancer. Using this data, we aim to identify clinical criteria to select patients amenable to conservative surgery, and to facilitate a more targeted approach in the management of advanced laryngeal cancer. METHODS: A retrospective study was performed in patients who underwent OPHL type II for laryngeal squamous cell carcinoma from January 2005 to December 2018. We analysed a total of 170 patients; 21(12.36%) cases were staged as pT2, 116 (68.23%) as pT3 and 33 (19.41%) as pT4a. RESULTS: Five-year overall survival (OS) was 80.9%, 79.3%, 70.4% for T2, T3 and T4 respectively. Disease-specific survival (DSS) was 90.4%, 85.3% and 77.4%. Posterior tumour extension, perineural invasion and N status showed to considerably influence survival in both uni- and multivariate analyses. CONCLUSION: The oncological outcomes from our study show that OPHL for advanced laryngeal cancer can guarantee a high percentage of success. Accurate patient selection is of utmost importance to differentiate advanced disease amenable to conservative surgery, and treatment options should consider selected criteria based on tumour and patient features.

An unusual approach for a cervical mass: sternotomy for the treatment of a giant cervico-thoracic lipoma.

BACKGROUND AND AIM: Lipoma is a benign mesenchymal tumor. It is a very common tumor and in 13% of cases occurs in head and neck. Giant lipomas are extraordinary and cervical involvement with mediastinal extension is an exceedingly rare presentation. Only a few cases of thoracic extension are reported in literature. METHODS: We describe the case of a 62-years-old man with a giant cervico-mediastinic lipoma which required a combined approach through cervicotomy and sternotomy to ensure surgical radicality. Differential diagnoses could be thymolipoma, liposarcoma or familiar lipomatosis. RESULTS: The mass was removed en-bloc with thymus and locoregional lymph nodes. The patient recovered uneventfully. CONCLUSIONS: The aim of this report is to discuss potential pitfalls of differential diagnosis and implementation of the therapeutic treatment. Focus on the relevance of performing fluorescence in situ hybridization (FISH) for MDM2 amplification is reported, a necessary technique for the differential diagnosis. (www.actabiomedica.it).

Lymphoepithelial carcinoma of larynx and hypopharynx: a systematic review and pooled analysis.

PURPOSE: To define the oncologic outcomes and the prognostic factors of laryngeal and hypopharyngeal lymphoepithelial carcinoma (LEC). METHODS: A systematic review and individual patient data analysis were performed according to the PRISMA guidelines. A total of 41 patients (males: 37; mean age: 63.1, standard deviation: 10.0) were included. RESULTS: The median follow-up time was 36.0 months (interquartile range, IQR: 11.5-73.5), while the median overall survival (OS) time was 96 months (IQR: 39.0-120.0). Estimated disease-specific survival (DSS) rates (95% Confidence Interval, CI; number still at risk) at 1, 3, and 5 years were 94.4% (79.5-98.6; 31), 82.7% (62.7-92.5; 21), and 78.1% (56.8-89.7; 13), respectively. Estimated disease-free survival (DFS) rates (95% CI; number still at risk) at 1, 3, and 5 years were 92.1% (77.4-97.4; 31), 74.9% (55.6-86.8; 21), and 66.6% (46.1-80.8; 13), respectively. Patients undergoing primary surgery had a reduced chance of death from cancer than patients receiving primary radiotherapy (5-year DSS 85.6 vs. 56.2%; p = 0.04), while EBV positivity tend to be a negative prognostic factor (5-year DSS 100 vs. 66.7%; p = 0.05). CONCLUSIONS: Laryngeal and hypopharyngeal LEC is a rare disease with favorable survival. Further prospective multicenter studies are needed to make a reliable statement on prognosis and outcome, stratifying patients for different therapy regimens and tumor stages.

Role of Narrow Band Imaging Endoscopy in Preoperative Evaluation of Laryngeal Leukoplakia: A Review of the Literature.

INTRODUCTION: Leukoplakia is a precancerous lesion considered to be within the spectrum of histopathological results from parakeratosis, through stages of dysplasia to invasive cancer. Narrow band imaging (NBI) endoscopy has been introduced to improve early diagnosis of benign and malignant laryngeal lesions. The aim of this literature review was to evaluate the accuracy of preoperative evaluation of vocal fold leukoplakia with NBI endoscopy in comparison with histology. METHODS: A systematic review of the literature was conducted following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, using 3 different databases: PubMed, Embase, and Scopus. The included articles in the systematic review were identified combining each of the following terms: "narrow band imaging" OR "NBI," [AND] with each of these terms: "laryngeal leukoplakia," OR "vocal fold leukoplakia," OR "vocal cord leukoplakia." RESULTS: The articles that fully met the inclusion criteria were 5 case series, conducted between January 2010 and February 2018, and published between 2017 and 2019. The selected articles included 312 patients (86% males and 14% females), affected by 382 vocal cord leukoplakia, evaluated with NBI endoscopy and that underwent surgical microlaryngoscopy with biopsy. Based on the studies included in the review, accuracy of NBI in predicting malignancy within leukoplakia ranged from 81% to 97.8%, demonstrating to be an accurate method to predict the risk of malignant transformation of vocal fold leukoplakia. CONCLUSION: Narrow band imaging can help otolaryngologists in the decision-making process on the necessity to perform a biopsy and transoral surgery or long-term follow-up. Larger studies are necessary to confirm the high association of NBI evaluation of the epithelium surrounding the leukoplakia with the histological diagnosis.

Cell-Free Human Papillomavirus-DNA for Monitoring Treatment Response of Head and Neck Squamous Cell Carcinoma: Systematic Review and Meta-Analysis.

OBJECTIVES/HYPOTHESIS: The aim of this study was to assess the value of cell-free human papillomavirus-DNA (cfHPV-DNA) as a diagnostic test for the post-treatment surveillance of patients with HPV-positive head and neck squamous cell carcinoma (HNSCC) through a systematic review and meta-analysis. STUDY DESIGN: Systematic review and meta-analysis. METHODS: A literature search was conducted in three databases (MEDLINE, Embase, and Scopus) in January 2021. The population included patients with HPV-positive HNSCC. The intervention was the use of the repeated liquid biopsy with circulating HPV-DNA detection during follow-up. The outcome was to establish the value of cfHPV-DNA as a diagnostic test for the post-treatment surveillance of patients with HPV-positive HNSCC. RESULTS: Ten studies included in the meta-analysis provided a total of 457 patients with HPV-positive HNSCC. The meta-analytic study estimated the diagnostic performance of cfHPV-DNA as follows: pooled sensitivity and specificity of 0.65 (95% confidence interval [CI]: 0.40-0.84) and 0.99 (99% CI: 0.96-0.99), respectively; positive and negative likelihood ratios of 62.5 (99% CI: 22.9-170.2) and 0.05 (99% CI: 0.013-0.24), respectively; and pooled diagnostic odds ratio of 371.66 (99% CI: 60.4-2286.7). CONCLUSION: Currently, the follow-up protocol for HNSCC patients includes routine clinical evaluation and radiological imaging. Biomarkers to monitor this disease are not established. Considering its high specificity, cfHPV-DNA represents a potential confirmatory test in the case of positive positron emission tomography and computed tomography. In the near future, cfHPV-DNA could be used as a biomarker for monitoring the treatment response during the clinical trials of de-escalation therapy or immunotherapy. Larger sample sizes and the homologation of study protocols and methodology are needed to better establish its utility in the clinical practice. Laryngoscope, 132:560-568, 2022.