Interdisciplinary management of skin cancer. / Die interdisziplinäre Behandlung von Hautkrebs.

The interdisciplinary treatment of skin cancer in the head and neck area requires close collaboration between different specialist disciplines. The most common non-melanoma skin cancer tumor entities are cutaneous squamous cell carcinoma and basal cell carcinoma as well as their precursor lesions. One of the less common tumors is Merkel cell carcinoma, which also occurs primarily in light-exposed areas and, in contrast to squamous and basal cell carcinoma, is more likely to metastasize. Due to the low tendency of basal cell carcinoma as well as cutaneous squamous cell carcinoma to metastasize, a cure can often be achieved by surgery. If the tumor growth exceeds certain levels it may require collaboration between dermatology and otorhinolaryngology. The primary goal of this interdisciplinary collaboration is to achieve a functional, cosmetically and aesthetically acceptable result in addition to adequate tumor treatment. Depending on the stage of the tumor and the clinical course, a case may be discussed in an interdisciplinary tumor board in order to determine a personalised, appropriate and adequate treatment concept for each patient, including prevention, therapy and follow-up.

[Update: Epidemiology and Prevention of Oropharyngeal Cancer]. / Update: Epidemiologie und Prävention des Oropharynxkarzinoms.

Due to the association with the causal HPV-16 infection, the oropharyngeal carcinoma spreads into two separate entities depending on HPV-16 positivity. More recent data show a diversified picture of the importance and prevalence of the surrogate parameter p16 (discordance) for a definitive HPV-16 association, which varies worldwide. In the context of prevention options, vaccination is of major and HPV screening of healthy people only of little importance.

Early postnatal high-dose fat-soluble enteral vitamin A supplementation for moderate or severe bronchopulmonary dysplasia or death in extremely low birthweight infants (NeoVitaA): a multicentre, randomised, parallel-group, double-blind, placebo-controlled, investigator-initiated phase 3 trial.

BACKGROUND: Vitamin A plays a key role in lung development, but there is no consensus regarding the optimal vitamin A dose and administration route in extremely low birthweight (ELBW) infants. We aimed to assess whether early postnatal additional high-dose fat-soluble enteral vitamin A supplementation versus placebo would lower the rate of moderate or severe bronchopulmonary dysplasia or death in ELBW infants receiving recommended basic enteral vitamin A supplementation. METHODS: This prospective, multicentre, randomised, parallel-group, double-blind, placebo-controlled, investigator-initiated phase 3 trial conducted at 29 neonatal intensive care units in Austria and Germany assessed early high-dose enteral vitamin A supplementation (5000 international units [IU]/kg per day) or placebo (peanut oil) for 28 days in ELBW infants. Eligible infants had a birthweight of more than 400 g and less than 1000 g; gestational age at birth of 32+0 weeks postmenstrual age or younger; and the need for mechanical ventilation, non-invasive respiratory support, or supplemental oxygen within the first 72 h of postnatal age after admission to the neonatal intensive care unit. Participants were randomly assigned by block randomisation with variable block sizes (two and four). All participants received basic vitamin A supplementation (1000 IU/kg per day). The composite primary endpoint was moderate or severe bronchopulmonary dysplasia or death at 36 weeks postmenstrual age, analysed in the intention-to-treat population. This trial was registered with EudraCT, 2013-001998-24. FINDINGS: Between March 2, 2015, and Feb 27, 2022, 3066 infants were screened for eligibility at the participating centres. 915 infants were included and randomly assigned to the high-dose vitamin A group (n=449) or the control group (n=466). Mean gestational age was 26·5 weeks (SD 2·0) and mean birthweight was 765 g (162). Moderate or severe bronchopulmonary dysplasia or death occurred in 171 (38%) of 449 infants in the high-dose vitamin A group versus 178 (38%) of 466 infants in the control group (adjusted odds ratio 0·99, 95% CI 0·73-1·55). The number of participants with at least one adverse event was similar between groups (256 [57%] of 449 in the high-dose vitamin A group and 281 [60%] of 466 in the control group). Serum retinol concentrations at baseline, at the end of intervention, and at 36 weeks postmenstrual age were similar in the two groups. INTERPRETATION: Early postnatal high-dose fat-soluble enteral vitamin A supplementation in ELBW infants was safe, but did not change the rate of moderate or severe bronchopulmonary dysplasia or death and did not substantially increase serum retinol concentrations. FUNDING: Deutsche Forschungsgemeinschaft and European Clinical Research Infrastructures Network (ECRIN).

Cancer-associated financial burden in German head and neck cancer patients.

Background: The financial toxicity of cancer causes higher morbidity and mortality. As the financial burden due to head and neck cancer (HNC) in European healthcare systems with legally established compulsory health insurance is still poorly understood, we set up an investigation to assess the financial impact of HNC. Methods: Between August 2022 and March 2023, HNC consecutive patients (n = 209) attending the cancer aftercare program of a university hospital in an outpatient setting were surveyed utilizing self-administered questionnaires about their socioeconomic situation, income loss, and out-of-pocket payments (OOPPs). Results: The majority of HNC patients (n = 119, 59.5%) reported significant financial burden as a consequence of OOPP (n = 100, 50.0%) and/or income loss (n = 51, 25.5%). HNC patients reporting financial burden due to OOPP had on average 1,716 € per year costs related to their disease, whereas patients reporting an income loss had a mean monthly income loss of 620.53 €. Advanced UICC (7th edition, 2017) stage, T3 or T4 category, and larynx/hypopharynx cancer are significant predictors of financial burden. Conclusion: HNC survivors suffer from significant financial burden after HNC treatment, even in Germany with a healthcare system with statutory health insurance. The findings from this study offer valuable insights for healthcare professionals and policymakers, helping them acknowledge the economic impact of HNC.

S3 guideline "actinic keratosis and cutaneous squamous cell carcinoma" - update 2023, part 2: epidemiology and etiology, diagnostics, surgical and systemic treatment of cutaneous squamous cell carcinoma (cSCC), surveillance and prevention.

Actinic keratosis (AK) are common lesions in light-skinned individuals that can potentially progress to cutaneous squamous cell carcinoma (cSCC). Both conditions may be associated with significant morbidity and constitute a major disease burden, especially among the elderly. To establish an evidence-based framework for clinical decision making, the guideline "actinic keratosis and cutaneous squamous cell carcinoma" was updated and expanded by the topics cutaneous squamous cell carcinoma in situ (Bowen's disease) and actinic cheilitis. The guideline is aimed at dermatologists, general practitioners, ear nose and throat specialists, surgeons, oncologists, radiologists and radiation oncologists in hospitals and office-based settings, as well as other medical specialties, policy makers and insurance funds involved in the diagnosis and treatment of patients with AK and cSCC. A separate guideline exists for patients and their relatives. In this part, we will address aspects relating to epidemiology and etiology, diagnostics, surgical and systemic treatment of cutaneous squamous cell carcinoma (cSCC), surveillance and prevention.

Immune checkpoint blockade induced shifts in cytokine expression patterns in peripheral blood of head and neck cancer patients are linked to outcome.

Background: Immune-checkpoint blockade (ICB) of programmed-death-1 (PD-1) with pembrolizumab or nivolumab is approved for treating recurrent/metastatic (R/M) head and neck squamous cell carcinoma (HNSCC). NadiHN and ADRISK are phase IIB trials investigating in locally advanced (LA) HNSCC having low or high risk of recurrence the potential benefits from adding nivolumab to post-operative radiotherapy or pembrolizumab to cisplatin-based radio-chemotherapy. Methods: Along five randomized controlled ICB trials including NadiHN and ADRISK, blood samples were taken before and after starting ICB in n=25 patients. Concentrations of vascular endothelial growth factor A (VEGF), CCL2 (MCP-1), interleukin-6 (IL-6), IL-8, interferon-gamma (IFN-γ), and CXCL10 (IP-10) pre- and post-ICB in EDTA-anticoagulated plasma and serum were compared. We used receiver operating characteristic (ROC) curves to identify optimal cutoff for defining subgroups before analyzing overall survival (OS) applying Kaplan-Meier plots and multivariate Cox regression. Results: We detected huge heterogeneity between cytokine patterns in pre-and post-ICB plasma and serum. We observed high correlation between concentrations of some cytokines. Despite absent systematic OS differences after ICB with pembrolizumab or nivolumab or between LA-HNSCC versus R/M HNSCC patients, we noticed improved outcome of patients having lower IFN-γ concentrations pre- and post-ICB and following ICB reduced concentrations of VEGF, IL-6, and IL-8 but not MCP-1. Contrarily, increases in IL-6, IL-8, and VEGF levels correlated with impaired outcome. Multivariate Cox regression revealed five independent OS predictors among cytokines; using natural logarithms of their hazard ratios to estimate an individual's risk of dying, three cytokine-expression pattern (CEP)-risk groups with no death within mean (95% confidence interval) follow-up of 29.2 (22.1-36.2) months and median OS of 11.3 (8.8-13.8) and 2.9 (0.4-5.4) months were found. Conclusion: Whereas individual pre- or post-ICB cytokine concentrations in serum or plasma alone failed to predict the survivor group, CEP-risk groups may support the identification of individual patients with long-lasting benefit from ICB.

Oral health in patients with different sites of head and neck squamous cell carcinoma is not different.

Oral health might not only act as risk factor for head and neck squamous cell carcinoma (HNSCC), but might also have a predictive value for the patients' survival. Currently, information on the effect of oral health on survival of patients with different sites of HNSCC is lacking. This single-center retrospective study aimed to compare oral health in patients with different sites of HNSCC and to analyse whether oral health is associated with survival in the different subsets of HNSCC patients. Dental records of HNSCC patients referred for dental assessment prior to radio(chemo)therapy were included. Patient-related parameters (age at time of diagnosis, sex, tobacco exposure, alcohol consumption, HPV status), treatment data (primary treatment, intent), performance status, tumor demographics (anatomical site, TNM staging), and oral health parameters (DMFT, periodontal health, teeth with/without root canal treatment and with/without periodontitis apicalis) were obtained. Oral health parameters were compared between different anatomical sites. Survival of all HNSCC patients and of individual subsets was assessed using Kaplan-Meier statistics, and the effect of tumor demographics, patient-related parameters, and oral health on survival was analysed by cox regression analyses (α = 5%). 371 patients with HNSCC (oral: n = 86, oropharyngeal: n = 174, hypopharyngeal: n = 59, laryngeal: n = 15, other: n = 37) were included. Oral health parameters did not differ between subsets (padj.≥0.199). Five-year cumulative survival of HNSCC patients amounted to 78.6%. Only for HNSCC originating in the oral cavity and oropharynx, survival was associated with the treatment intent (p = 0.015) or performance status (p = 0.007) in the multivariable analyses, respectively. Within the limitations of this study, oral health was not different between different subsets and had no significant effect on survival of HNSCC patients.

Is High-Risk Sexual Behavior a Risk Factor for Oropharyngeal Cancer?

(1) Background: Several lines of evidence established a link between high-risk (HR) sexual behavior (SB), the persistence of human papillomavirus (HPV) DNA in saliva, and the presence of oncogenic HR-HPV subtypes in oropharyngeal squamous cell carcinoma (OPSCC). A highly influential case-control study by D'Souza et al. comparing OPSCC patients and ENT patients with benign diseases (hospital controls) established HR-SB as a putative etiological risk factor for OPSCC. Aiming to replicate their findings in a nested case-control study of OPSCC patients and propensity score (PS)-matched unaffected controls from a large population-based German cohort study, we here demonstrate discrepant findings regarding HR-SB in OPSCC. (2) Methods: According to the main risk factors for HNSCC (age, sex, tobacco smoking, and alcohol consumption) PS-matched healthy controls invited from the population-based cohort study LIFE and HNSCC (including OPSCC) patients underwent interviews, using AUDIT and Fagerström, as well as questionnaires asking for SB categories as published. Afterwards, by newly calculating PSs for the same four risk factors, we matched each OPSCC patient with two healthy controls and compared responses utilizing chi-squared tests and logistic regression. (3) Results: The HNSCC patients and controls showed significant differences in sex distribution, chronologic age, tobacco-smoking history (pack years), and alcohol dependence (based on AUDIT score). However, PS-matching decreased the differences between OPSCC patients and controls substantially. Despite confirming that OPSCC patients were more likely to self-report their first sexual intercourse before age 18, we found no association between OPSCC and HR-SB, neither for practicing oral-sex, having an increased number of oral- or vaginal-sex partners, nor for having casual sex or having any sexually transmitted disease. (4) Conclusions: Our data, by showing a low prevalence of HR-SB in OPSCC patients, confirm findings from other European studies that differ substantially from North American case-control studies. HR-SB alone may not add excess risk for developing OPSCC.

Postoperative adjuvant radiochemotherapy with cisplatin versus adjuvant radiochemotherapy with cisplatin and pembrolizumab in locally advanced head and neck squamous cell carcinoma- the study protocol of the Adrisk trial.

Most of the patients with head and neck squamous cell carcinoma (HNSCC) are diagnosed with locally advanced disease. Standards of care for curative-intent treatment of this patient group are either surgery and adjuvant radio(chemo)therapy (aRCT) or definitive chemoradiation. Despite these treatments, especially pathologically intermediate and high-risk HNSCC often recur. The ADRISK trial investigates in locally advanced HNSCC and intermediate and high risk after up-front surgery if the addition of pembrolizumab to aRCT with cisplatin improves event-free sur-vival compared to aRCT alone. ADRISK is a prospective, randomized controlled investiga-tor-initiated (IIT)-phase II multicenter trial within the German Interdisciplinary Study Group of German Cancer Society (IAG-KHT). Patients with primary resectable stage III and IV HNSCC of the oral cavity, oropharynx, hypopharynx and larynx with pathologic high (R1, extracapsular nodal extension) or intermediate risk (R0 <5 mm; N≥2) after surgery will be eligible. Two hun-dred forty patients will be randomly assigned (1:1) to either standard aRCT with cisplatin (standard arm) or aRCT with cisplatin + pembrolizumab (200 mg iv, in 3-week cycle, max. 12 months) (interventional arm). Endpoints are event-free and overall survival. Recruitment started in August 2018 and is ongoing.

Effect of postoperative systemic prednisolone on short-term and long-term outcomes in chronic rhinosinusitis with nasal polyps: A multi-centered randomized clinical trial.

Introduction: The objective of this study was to determine whether postoperative additive systemic steroid administration in chronic rhinosinusitis with nasal polyps (CRSwNP) impacted selected endoscopic, subjective and objective outcome measures. Methods: This was a prospective, randomized, double-blind, placebo-controlled, noninferiority multicenter trial of n=106 patients with CRSwNP. All patients underwent primary functional endoscopic sinus surgery (FESS) followed by topical nasal steroids. Patients were randomized to a systemic steroid or placebo for 1 month. Patients were followed up for 2 years over 9 time points. The primary outcome measures were the differences between groups with respect to the nasal polyp score (NPS) and sinonasal quality of life (SNQoL). Secondary outcome measures included interactions with respect to the Lund-Kennedy score (LKS), sinonasal symptoms, general quality of life (GQoL), 16-item odor identification test scores, recurrence rates, need for revision surgery and mucus biomarker levels. Results: 106 patients were randomized to either the placebo or the systemic steroid group (n=53 per group). Postoperative systemic steroids were not superior to placebo with respect to all primary (p= 0.077) and secondary outcome measures (p>0.05 for all). Reported adverse events were similar between the two groups. Conclusion: In conclusion, the addition of postoperative systemic steroids after primary FESS did not confer a benefit over topical steroid nasal spray alone with respect to NPS, SNQOL, LKS, GQOL, sinonasal symptoms, smell scores, recurrence rates, the need for revision surgery or biomarkers over a short-term follow-up of up to 9 months and a long-term follow-up of up to 24 months in CRSwNP patients. Functional endoscopic surgery did, however, show a strong effect on all outcome measures, which remained relatively stable up to the endpoint at 2 years.

Oral health in HPV-positive and HPV-negative patients with oropharyngeal squamous cell carcinoma.

This study compared oral health in oropharyngeal squamous cell carcinoma (OPSCC) patients with positive or negative human papillomavirus (HPV) status and analysed whether oral health was associated with survival. Patients referred for dental assessment prior to radio(chemo)therapy between 2009 and 2019 were included. Patient-related risk factors for OPSCC (alcohol, tobacco, HPV status), age, sex, treatment (primary treatment, intent), performance status, tumor/node/metastasis (TNM) staging, and oral health parameters (DMFT, periodontal status, teeth with/without root canal treatment and with/without periodontitis apicalis) were compared between HPV-negative and HPV-positive patients. Survival was assessed using Kaplan-Meier statistics. The effect of patient-related risk factors and oral health parameters was analysed by cox regression analyses (α=5%). A total of 119 patients (n=50 HPV-negative, n=69 HPV-positive) was included. HPV-positive patients showed more present teeth, a higher number of filled teeth, were less often edentulous and presented a lower DMFT compared to HPV-negative patients (padj.≤0.003). Among dentulous patients, HPV-positive patients showed more present teeth and fewer teeth with periodontitis apicalis lacking a root canal treatment (padj.≤0.036). Survival probability differed between groups (p=0.006) and trended towards being associated with HPV status, tobacco exposure, performance status, T stage, N stage, and the number of missing or filled teeth as well as the number of root canal treated teeth with periodontitis apicalis and the number of teeth with periodontitis apicalis lacking a root canal treatment (p≤0.077). However, only tobacco exposure, performance status, and the number of teeth with periodontitis apicalis lacking a root canal treatment in dentulous patients remained significant in the multivariate analyses (p≤0.047). HPV-negative patients with OPSCC showed a poorer oral health compared to HPV-positive patients, but survival was not associated with oral health.

Vascular Malformations of the Head and Neck in Children.

BACKGROUND/AIM: Vascular malformations are congenital abnormalities that result from disturbances in the embryologic development of the vascular system. A retrospective study at a single institution was performed to determine the localization and treatment patterns for vascular malformations in children. PATIENTS AND METHODS: A total of 198 pediatric patients were identified. Age at diagnosis and presentation, sex, localization, diagnostics, and therapy were described. RESULTS: The most common diagnosis was lymphatic malformation (LM, 58.6%), followed by venous (VM, 31.8%) and arteriovenous malformation (AVM, 4.5%). The mean age at diagnosis was 2.2 years, while the mean age at presentation at our hospital was 7.2 years. The sex ratio showed a female predominance (1.44:1), which was most evident in children with AVM. The neck, cheek/parotid gland and oral cavity were the most predominant locations. Half of the patients required at least one intervention at our hospital. Especially, CM and LM were managed by watch-and wait, whereas lymphovenous malformation (LVM) and AVM were most often treated. Treatment differed between the various malformation types, the most common used treatment was conventional surgery followed by laser therapy. In case of treatment, the average number of procedures in our hospital was 1.58 for VM, 1.53 for LM, 1.33 for AVM, and 1.0 for LVM. CONCLUSION: In children with vascular malformations interventional treatment is often necessary, in many cases more than one treatment step is needed. Correct identification of the malformation type is important for optimal treatment and appropriate care of patients with vascular malformations.

Association between malformation type, location and functional deficits in lymphatic malformations of the head and neck in children.

PURPOSE: Lymphatic malformations (LM) are congenital malformations of the lymphatic system, mainly located in the head and neck area. They can be staged based on location according to de Serres and based on different morbidity items using the Cologne Disease Score (CDS), a clinical staging system. In many cases, functional impairment greatly affects the life of patients suffering from lymphatic malformations. The present study aims to analyze a cohort of pediatric patients with LM. METHODS: A retrospective analysis of 144 pediatric patients with head and neck LM was performed. Location, type of malformation (microcystic, macrocystic, mixed), scoring according to two different scoring systems and therapy were analyzed. Kruskal-Wallis test was used to analyze the difference in CDS between the patient groups and Dunn's test was used for post-hoc pairwise comparison. RESULTS: The average age at presentation was 6.1 years. The most common sites were neck (47%), cheek/parotid gland (26%), tongue (17%) and orbit (8%). Macrocystic malformations dominated the lateral neck, while microcystic malformations were predominantly localized in the tongue and floor of mouth. Macrocystic malformations (mean CDS 9.44) were associated with significantly better CDS than microcystic (mean CDS 7.11) and mixed (mean CDS 5.71) malformations (p < 0.001). LM in stage V according to de Serres had the lowest values (mean CDS: 4.26). The most common therapeutic procedures were conventional surgical (partial) resection, laser therapy and sclerotherapy with OK-432. CONCLUSIONS: There is an association between malformation type, location according to de Serres and CDS in children with LM of the head and neck. Patients with microcystic and mixed malformations in stage V had lowest CDS levels.

Outcome differences in HPV-driven head and neck squamous cell carcinoma attributable to altered human leukocyte antigen frequencies.

Background: Effective immune surveillance requires a functioning immune system and natural killer (NK) and T cells for adequate innate and antigen-specific immune responses critically depending on human leukocyte antigens (HLAs) and haplotypes representing advantageous combinations of HLA antigens. Recently, we reported a link between altered frequencies of HLA alleles and haplotypes and developing head and neck squamous cell carcinoma (HNSCC). Whereas the majority of HNSCCs seem to be related to classical risk factors alcohol and tobacco, a subset of HNSCC and especially oropharyngeal squamous cell carcinoma (OPSCC) were etiologically linked to human papillomavirus (HPV) recently. Here, we demonstrate in HPV-driven (p16-positive high risk-HPV DNA-positive) HNSCC a deviating distribution of HLA antigens and haplotypes and their relevance to outcome. Methods: Leukocyte DNA of n = 94 HPV-driven HNSCC patients (n = 57 OPSCC, n = 37 outside oropharynx) underwent HLA SSO typing, allowing allele, antigen (allele group), and haplo-typing. Besides comparing these frequencies with those of German blood donors, we analyzed their impact on outcome using Kaplan-Meier plots and Cox proportional hazard regression. Results: Antigen and haplotype frequencies demonstrate enrichment of rare antigens and haplotypes. The HLA score for unselected HNSCC patients was not predictive for outcome here. However, together with alcohol consumption, tobacco smoking, T category, and extranodal extension of locoregional metastases and treatment applied, eight HLA traits allow for predicting progression-free and tumor-specific survival. Conclusion: Patients can be categorized into low, intermediate-low, intermediate-high, and high risk groups. Using a new PFS risk score for HPV-driven HNSCC may allow to improve prognostication.

Frailty and Increased Levels of Symptom Burden Can Predict the Presence of Each Other in HNSCC Patients.

Frailty is an important risk factor for adverse events (AEs), especially in elderly patients. Therefore, assessing frailty before therapy is recommended. In head and neck squamous cell carcinoma (HNSCC) patients, frailty is prognostic for severe postoperative complications and declining quality of life (QoL) after HNSCC treatment. Thus, assessment of frailty may help to identify individuals at risk for AE caused by oncologic therapy. We investigated the relationship between frailty and symptom burden to better understand their interaction and impact on HNSCC patients. In this prospectively designed cross-sectional study, the presence of frailty and symptom burden was assessed by using the Geriatric 8 (G8) and Minimal Documentation System (MIDOS2) questionnaires. A total of 59 consecutively accrued patients with a first diagnosis of HNSCC before therapy were evaluated. Patients were considered frail at a total G8 score ≤ 14. The MIDOS2 symptom burden score was considered pathological with a total score ≥ 4 or any severe symptom (=3). Statistical correlations were analyzed using Spearman and Pearson correlation. Receiver operator characteristic (ROC) curves were used to analyze the potential of predicting frailty and MIDOS2. p-values < 0.05 were considered significant. A total of 41 patients (69.5%) were considered frail, and 27 patients (45.8%) had increased symptom burden. "Tiredness" was the most common (overall rate 57.8%) and "Pain" was the most often stated "severe" symptom (5 patients, 8.5%). G8 and MIDOS2 correlated significantly (ρ = -0.487, p < 0.001; r = -0.423, p < 0.001). Frailty can be predicted by MIDOS2 symptom score (AUC = 0.808, 95% CI 0.698-0.917, p < 0.001). Vice versa, the G8 score can predict pathological symptom burden according to MIDOS2 (AUC = 0.750, 95% CI 0.622-0.878, p < 0.001). Conclusions: The strong link between frailty and increased symptom burden assessed by G8 or MIDOS2 indicates a coherence of both risk factors in HNSCC patients. Considering at least one of both scores might improve the identification of individuals at risk and achieve higher QoL and reduced complication rates by decision making for appropriate therapy regimens.

High-Risk Human Papillomavirus (HR-HPV) DNA Detection in Mouthwashes for Diagnosis of HPV-Driven Oropharynx Cancer and Its Curative Therapy-A Feasibility Study.

Detection of p16 through immunohistochemistry (IHC) is the standard for determining the HPV status of the tumor according the TNM eighth edition released in 2017 and has become crucial for determining the HPV status of oropharyngeal squamous cell carcinomas (OPSCC) with direct impact on staging and prognostication. In recent years, detection of HPV DNA in mouthwashes has been proposed as a noninvasive alternative, both for OPSCCs and for other head and neck squamous cell carcinomas (HNSCCs). However, the prospect of using the mouthwashes to monitor the response to therapy is unclear. To evaluate the effect of curative therapy on the detection of HPV DNA, we performed a prospective study comparing the detection frequency of high-risk HPV DNA (HR-HPV-DNA) in pre- and post-therapy mouthwashes. We collected 137 mouthwashes from 88 pathologically confirmed HNSCC patients for DNA isolation and HPV genotyping with the Inno-LiPA assay. We show that HPV DNA in pretherapeutic mouthwashes can detect HPV-driven HNSCCs with a sensitivity of 50.0% and specificity of 85.4%, alongside a high negative predictive value of 79.5% and an accuracy of 74.5%. Furthermore, we observed a notable decrease in the detection frequency of HR-HPV-DNA after successful treatment (pre-therapy 50.0% (9/18) versus post-therapy 9.7% (3/28)). However, the comparatively low sensitivity regarding detection of HPV-driven OPSCC argues against its use in clinical routine.

Prognostic Significance of the Nodal Ratio and Number of Positive Nodes in Patients With Squamous Cell Carcinomas of the Head and Neck.

BACKGROUND/AIM: The lymph node status has high prognostic relevance in head and neck squamous cell carcinoma (HNSCC). This study aimed to address the hypothesis that the number of positive nodes and the nodal ratio have a prognostic impact on survival in HNSCC. PATIENTS AND METHODS: A retrospective analysis of 221 patients with HNSCC and clinical N+ status who underwent a neck dissection during primary surgery or after definitive radio(chemo)therapy was performed. The possible influence of age, sex, TNM stage, number of positive nodes and nodal ratio on survival was analyzed by univariate and multivariate Cox models and log-rank tests. RESULTS: On average, 30.1 lymph nodes were removed and 4.96 metastases were detected. The mean nodal ratio was 9.4%, the median nodal ratio was 5.3%. Multivariate analysis demonstrated a nodal ratio of ≥6-<12.5% [hazard ratio (HR)=2.33, 95% confidence interval (CI)=1.24-4.37; p=0.008] and of ≥12.5% (HR=2.86, 95% CI=1.40-5.84; p=0.004) compared to nodal ratio 0, number of positive nodes pN=1 compared to number of positive nodes=0 (HR=2.02, 95% CI=1.08-3.80. p=0.029), as well as N3 compared to N0 (HR=8.10, 95% CI=1.89-34.66; p=0.005), and Mx compared to M0 (HR of 2.76, 95% CI=1.59-4,79, p≤0.001) were of main importance for poor prognosis. Postoperative radio(chemo)therapy after surgery was associated with prolonged survival in multivariate analysis (HR=0.37, 95% CI=0.24-0.57; p≤0.001). CONCLUSION: The nodal ratio and number of positive nodes seem to have a high prognostic impact in patients with HNSCC and can be of value in identifying patients at high risk who warrant more aggressive therapy.