Submandibular gland involvement in oral cavity squamous cell carcinoma: a retrospective multicenter study.

BACKGROUND: The submandibular gland (SMG) is routinely excised during neck dissection. Given the importance of the SMG in saliva production, it is important to understand its involvement rate by cancer tissue and the feasibility of its preservation. METHODS: Retrospective data were collected from five academic centers in Europe. The study involved adult patients affected by primary oral cavity carcinoma (OCC) undergoing tumor excision and neck dissection. The main outcome analyzed was the SMG involvement rate. A systematic review and a meta-analysis were also conducted to provide an updated synthesis of the topic. RESULTS: A total of 642 patients were enrolled. The SMG involvement rate was 12/642 (1.9%; 95% CI 1.0-3.2) when considered per patient, and 12/852 (1.4%; 95% CI 0.6-2.1) when considered per gland. All the glands involved were ipsilateral to the tumor. Statistical analysis showed that predictive factors for gland invasion were: advanced pT status, advanced nodal involvement, presence of extracapsular spread and perivascular invasion. The involvement of level I lymph nodes was associated with gland invasion in 9 out of 12 cases. pN0 cases were correlated with a reduced risk of SMG involvement. The review of the literature and the meta-analysis confirmed the rare involvement of the SMG: on the 4458 patients and 5037 glands analyzed, the involvement rate was 1.8% (99% CI 1.1-2.7) and 1.6% (99% CI 1.0-2.4), respectively. CONCLUSIONS: The incidence of SMG involvement in primary OCC is rare. Therefore, exploring gland preservation as an option in selected cases would be reasonable. Future prospective studies are needed to investigate the oncological safety and the real impact on quality of life of SMG preservation.

Surgeons reaching satisfying outcomes without surgery: nasal dorsum skin cancer recurrence treated with electrochemotherapy.

Cutaneous squamous cell carcinoma of the head and neck district are generally treated with surgery. Surgery is the standard treatment in early stages and local advanced tumors, followed by adjuvant therapy, radiation or concurrent chemoradiation therapy. Local recurrence treatment depends on previous therapies, though radical surgery is often the first choice at the expense of anatomy preservation. We present the case of a patient with cutaneous squamous cell carcinoma of the nasal dorsum which relapsed after surgery and radiation therapy. The patient refused radical surgery and electrochemotherapy under general anesthesia was administered. After 6 months from treatment, the patient showed a complete clinical response. Electrochemotherapy could be considered as an alternative to surgery in small lesion when other approaches are refused.

Myxoid Liposarcoma Metastasizing to the Parotid Gland.

Localization of metastases into the parotid gland is a very uncommon event. Usually they arise from primary tumors located in the head and neck, mainly melanoma or epidermoid carcinoma of the skin, while other histotypes, from others anatomical districts, hardly have a metastatic spread to the parotid. Myxoid liposarcoma (MLS) is a rare malignant tumor of the soft tissue that mainly occurs in the extremities, representing the second most common subtype of liposarcoma. Although it is typical for liposarcomas to metastasize to the lungs, it is known that MLS can spread also to extra pulmonary sites. The authors report a case of myxoid liposarcoma of the left thigh in a 64-year-old man, with an unusual metastatic double presentation to the contralateral forearm first and to the parotid gland then. MLS with metastatic disease to the parotid gland is an extremely rare event with very few cases reported in the English literature.

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.

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.

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.

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).

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.

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.

Early Onset of SARS-COV-2 Antibodies after First Dose of BNT162b2: Correlation with Age, Gender and BMI.

BACKGROUND: The first goal of the study was to analyse the antibody titre 21 days after the first dose of the BNT162b2 vaccine in a group of 252 healthcare workers (HCW). The second goal was to analyse how the antibody titre changes in correlation with age, gender and body mass index (BMI). METHODS: Participants had a nasopharyngeal swab for SARS-CoV-2 and were assessed for the presence of SARS-CoV-2 antibodies at baseline and 21 days after the BNT162b2 priming dose. RESULTS: First dose of BNT162b2 activated immune responses in 98% of the participants. Five HWC had no increase in antibody titre 21 days after the first dose. Antibody titre was greater in young (<38 years) vs. older participants (<38 vs. 47-56 p = 0.002; <38 vs. >56 p = 0.001). Higher antibody levels were detected in underweight vs. pre-obesity group (p = 0.026) and in normal-weight vs. pre-obesity group (p = 0.007). This association was confirmed after adjusting for age (p = 0.0001) and gender (p = 0.00001). CONCLUSIONS: Our study demonstrates that a single dose of BNT162b2 activates the immune response, and being young and normal-weight correlate positively with this response. Larger specifically designed clinical trials are needed to validate these results.

Initial observations on age, gender, BMI and hypertension in antibody responses to SARS-CoV-2 BNT162b2 vaccine.

BACKGROUND: Literature data suggests that age, gender and body mass index (BMI) could be associated with difference in immune responses to vaccines. The first goal of the study was to analyze the antibody titre seven days after the second dose of BNT162b2 vaccine in a group of 248 healthcare workers (HCWs). The second goal was to analyze how antibody titre changes in correlation with age, gender, BMI and hypertension. METHODS: An immunogenicity evaluation was carried out among HCWs vaccinated at the Istituti Fisioterapici Ospitalieri (IFO), Rome, Italy. All HCWs were asked to be vaccinated by the Italian national vaccine campaign at the beginning of 2021. 260 vaccinated HCWs were enrolled in the study. All eligible participants were assigned to receive the priming dose in two weeks' time and the booster dose exactly 21 days thereafter. Blood and nasopharyngeal swabs were collected at baseline and 7 days after second dose of vaccine. Quantitative measurements of IgG antibodies against S1/S2 antigens of SARS-CoV-2 were performed with a commercial chemiluminescent immunoassay. Presence of SARS-Cov-2 in nasopharyngeal swab was determined by commercial RT-PCR testing. FINDINGS: 248 HWCs were analyzed, 158 women (63.7%) and 90 men (36.3%). After the second dose of BNT162b2 vaccine, 99.5% of participants developed a humoral immune response. The geometric mean concentration of antibodies among the vaccinated subjects after booster dose (285.9 AU/mL 95% CI: 249.5-327.7) was higher than that of human convalescent sera (39.4 AU/mL, 95% CI: 33.1-46.9), with p<0.0001. Multivariate linear regression analysis of AU/mL by age, gender and BMI multivariate was performed by the inclusion of covariates. This analysis demonstrated that age (p<0.0001) and gender (p = 0.038) are statistically associated with differences in antibody response after vaccination, whereas BMI and hypertension have no statistically significant association (p = 0.078 and p = 0.52 respectively). INTERPRETATION: 99.5% of HCW developed a humoral immune response and female and young participants seem to have an increased capacity to mount humoral immune responses. BMI and hypertension seem not associated with difference in immune response to the vaccine. FUNDING: None.

Antibody Persistence 6 Months Post-Vaccination with BNT162b2 among Health Care Workers.

BACKGROUND: We present immunogenicity data 6 months after the first dose of BNT162b2 in correlation with age, gender, BMI, comorbidities and previous SARS-CoV-2 infection. METHODS: An immunogenicity evaluation was carried out among health care workers (HCW) vaccinated at the Istituti Fisioterapici Ospitalieri (IFO). All HCW were asked to be vaccine by the national vaccine campaign at the beginning of 2021. Serum samples were collected on day 1 just prior to the first dose of the vaccine and on day 21 just prior to the second vaccination dose. Thereafter sera samples were collected 28, 49, 84 and 168 days after the first dose of BNT162b2. Quantitative measurement of IgG antibodies against S1/S2 antigens of SARS-CoV-2 was performed with a commercial chemiluminescent immunoassay. RESULTS: Two hundred seventy-four HWCs were analyzed, 175 women (63.9%) and 99 men (36.1%). The maximum antibody geometric mean concentration (AbGMC) was reached at T2 (299.89 AU/mL; 95% CI: 263.53-339.52) with a significant increase compared to baseline (p < 0.0001). Thereafter, a progressive decrease was observed. At T5, a median decrease of 59.6% in COVID-19 negative, and of 67.8% in COVID-19 positive individuals were identified with respect to the highest antibody response. At T1, age and previous COVID-19 were associated with differences in antibody response, while at T2 and T3 differences in immune response were associated with age, gender and previous COVID-19. At T4 and T5, only COVID-19 positive participants demonstrated a greater antibody response, whereas no other variables seemed to influence antibody levels. CONCLUSIONS: Overall our study clearly shows antibody persistence at 6 months, albeit with a certain decline. Thus, the use of this vaccine in addressing the COVID-19 pandemic is supported by our results that in turn open debate about the need for further boosts.

Evolving Profile of HPV-Driven Oropharyngeal Squamous Cell Carcinoma in a National Cancer Institute in Italy: A 10-Year Retrospective Study.

Globally, 30% of oropharyngeal carcinomas (OPSCC) are caused by Human Papillomavirus (HPV). Recently, increasing incidence trends for HPV-driven OPSCC have been reported in many countries and changes in the typical HPV-positive OPSCC patient have been recorded, with an increase in the median age and diagnoses in women. We investigated the characteristics of the OPSCC patients attending an Italian Cancer Institute from 2010 to 2019 and assessed possible changes overtime of demographic, behavioral, and clinico-pathologic variables of HPV-driven OPSCC. Overall, 339 OPSCCs were evaluated. HPV-DNA and p16 positivity were 48.7% and 55.2%, respectively, with an HPV-driven fraction (i.e., HPV-DNA+/p16+) of 48.3%. We observed a significant increase overtime in the rate of HPV-associated cases (53.7% in 2015-2019 vs. 40.3% in 2010-2014, p = 0.019). The rate of HPV-driven cases was significantly higher among women, never smokers, patients with T1-T2 tumors, and with nodal involvement. A trend was also observed toward an increase in HPV-driven OPSCCs among patients >61 years, women, former smokers, and patients with no nodal involvement in 2015-2019. Our findings consolidate the observation that HPV-associated OPSCCs are also increasing in Italy. Moreover, they suggest that the profile of the HPV-driven OPSCC patient might be changing.

Literature in the time of COVID-19: The "phase two".

The sudden onset of the COVID-19 pandemic has put a strain on the whole scientific world. We assisted to a tremendous effort by researchers with the final goal of achieving a better management of COVID-19 patients. The world of otorhinolaryngology, likewise, has not been exempt from this commitment to research. In this commentary we perform a bibliometric review of the available academic literature about COVID-19 in the top 20-ranked ENT journal, with the goal of providing an overview of what has been published to date and encouraging a shift towards quantitative research.

Transoral robotic retropharyngeal lymph node dissection in a recurrent head and neck carcinoma.

BACKGROUND: A step-by-step demonstration of the transoral robotic surgical approach (TORS) used in retropharyngeal node dissection (RND) in a recurrent head and neck carcinoma. METHODS: Clinical human study of TORS RND via en bloc resection using a daVinci Si system (Intuitive Surgical, Inc., Sunnyvale, California). RESULTS: A daVinci Si system provided sufficient access, reach, and visualization to perform TORS-RND. Access and exposure were achieved with a Feyh-Kastenbauer (FK) retractor (Gyrus Medical Inc., Tuttlingen, Germany). Two surgical instruments and one 3D camera arm can be deployed with minimal collision or restriction of arm movement. CONCLUSIONS: Routine transcervical, transparotid, and transmandibular RNDs can provoke potentially serious surgical morbidities and complications. This study demonstrates the technical feasibility of TORS RND in a 68-year-old man.