IntroductionThe purpose of this study was to test whether the 8th edition of the AJCC/UICC TNM staging system (UICC) precisely differentiates between stages and reflects disease outcome in human papilloma virus (HPV)-associated oropharyngeal squamous cell carcinoma (OPSCC).Patients and methodsOPSCC patients that were diagnosed between 2000 and 2016 were included in this analysis and HPV status was determined by combined DNA and p16 testing. Stratification was done according to 7th and 8th UICC staging rules. Incidence trends of HPV-associated tumorigenesis, 5-year overall survival (OS) according to tumor stages as well as the influence of therapy and prognostic factors toward the outcome were calculated using Kaplan–Meier method and Cox proportional-hazards model.ResultsA significant increase [2000; n = 8/39 (21%)–2015; n = 17/32 (53%); p = 0.002] in HPV-associated OPSCC was seen in the observation period. Together, 150/599 (25.0%) of the patients had HPV-driven OPSCC and 64.7% of curative treatments in all OPSCC patients included upfront surgery of the primary and the neck. 7th edition staging rules led to no discrimination in all respective four UICC stages in HPV OPSCC underlining the need for new staging rules. However, only discrimination between stages I vs. II and III vs. IV was significant in our patients with HPV-OPSCC (94.4 vs. 77.5%; p = 0.031 and 63.9 vs. 25.0%; p = 0.013), and stages II vs. III did not differ in OS rates (p = 0.257), when applying the new staging rules. For HPV-negative OPSCC, significant outcome differences were only seen between UICC stages III vs. IV (57.6 vs. 35.2%; p = 0.012).DiscussionWhile the 7th edition of UICC shows invalid discrimination between stages, the 8th edition is more suitable for HPV-associated carcinoma. Due to lack of differentiation between stages II and III further adaption is essential.

Background:Upfront surgery is a valuable treatment option for oropharyngeal squamous cell carcinoma (OPSCC) and risk stratification is emerging for treatment de-escalation in human papillomavirus (HPV)-related OPSCC. Available prognostic models are either based on selected, mainly non-surgically treated cohorts. Therefore, we investigated unselected OPSCC treated with predominantly upfront surgery.Methods:All patients diagnosed with OPSCC and treated with curative intent between 2000 and 2009 (n=359) were included. HPV association was determined by HPV-DNA detection and p16INK4a immunohistochemistry. Predictors with significant impact on overall survival (OS) in univariate analysis were included in recursive partitioning analysis.Results:Risk models generated from non-surgically treated patients showed low discrimination in our cohort. A new model developed for unselected patients predominantly treated with upfront surgery separates low-, intermediate- and high-risk patients with significant differences in 5-year OS (86%, 53% and 19%, P<0.001, respectively). HPV status is the most important parameter followed by T-stage in HPV-related and performance status in HPV-negative OPSCC. HPV status and ECOG remained important parameters in risk models for patients treated with or without surgery.Conclusions:Regardless of treatment strategies, HPV status is the strongest predictor of survival in unselected OPSCC patients. The proposed risk models are suitable to discriminate risk groups in unselected OPSCC patients treated with upfront surgery, which has substantial impact for design and interpretation of de-escalation trials.

Sialendoscopy is an established, minimally invasive technique to diagnose and treat obstructive disorders of major salivary glands. Knowledge about patient satisfaction and quality of life is limited. All patients who underwent sialendoscopy were prospectively followed and evaluated. To determine the quality of life after sialendoscopy, an established questionnaire was evaluated (Short-Form-36 Health Survey-SF-36). To determine patient satisfaction, a self-made questionnaire was applied and evaluated. Furthermore, postoperative follow-up examination and the amount of patients who could be saved from sialadenectomy were determined. Main reasons for sialendoscopy were recurrent or permanent swelling of the affected salivary gland. 46 patients were included, 52 sialendoscopies were performed. Immediately after sialendoscopy operative ablation of the respective gland was averted in 98.1 % of the patients. After the follow-up period of 225.4 ± 79.0 days operative ablation of the respective gland was avoided in 89.9 % of the patients. Overall, 85.2 % reported an improvement of symptoms during follow-up, however, values for role-physical functioning (p = 0.025) and bodily pain (p = 0.011) still showed a significant difference when compared to a matched reference group of healthy individuals. Significant negative influence factors towards the outcome were younger age, long-term duration of symptoms and selected SF-36 items (vitality, social functioning, and mental health). Operative ablation of major salivary glands can be avoided by means of sialendoscopy in high percentages during short-term. There seems to be a high patient satisfaction in these selected cases. The duration of preoperative symptoms appears to be an important factor predisposing towards poor satisfaction.

Background A remarkably better prognosis is associated with oropharyngeal squamous cell carcinomas (OPSCC) driven by human papillomaviruses (HPV) compared with HPV-negative OPSCC. Consequently, de-escalation of standard treatment has been suggested. Due to modest specificity rates, debates are ongoing, whether p16INK4a, a surrogate marker for HPV-driven OPSCC, is sufficient to correctly identify those tumours and avoid substantial HPV misattribution and thus undertreatment of patients by de-escalation. Robust data estimating the proportion of potentially undertreated patients are missing. Methods We assessed a large-scale cohort of consecutively included OPSCC diagnosed between 2000 and 2017 for HPV–DNA, HPV genotypes, p16INK4a expression and multiple tumour- and patient-related risk factors, and investigated their impact on patients’ survival in comprehensive uni- and multivariate analyses. Results Aetiological relevance of HPV (p16INK4a- and high-risk HPV–DNA-positivity) was detected in 27.1% (n = 192) of OPSCC, with HPV16 being the most abundant HPV type (94.6%). In 5.5% patients (n = 39), p16INK4a overexpression but no HPV–DNA was detected. Principal component and survival analyses revealed that 60.6% of these p16INK4a-positive OPSCC lacking HPV–DNA did not resemble HPV16-driven but HPV-negative OPSCC regarding risk-factor profile and overall survival. Notably, this group represented 10.6% of all p16INK4a-overexpressing OPSCC. Conclusions p16INK4a as a single marker appears insufficient to indicate OPSCC patients suitable for treatment de-escalation.

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Human papillomavirus(HPV)-related head and neck cancer is recognized as a distinct tumor entity with rising incidence reported for several countries. These tumors arise from squamous cells, typically in the oropharynx. In contrast to cancer associated with other risk factors, HPV-related cancer is driven by viral oncoprotein activity and has individual profiles regarding protein expression, and genetic and epigenetic alterations. Molecular characteristics are p16^IN4A overexpression, absence of p53 inactivating mutations, and PI3K/AKT and Wnt pathway modulation. Patients with HPV-related head and neck cancer have improved survival compared to those with HPV-negative tumors, and p16^INK4A staining has been introduced into tumor staging recently. However, no specific or toxicity-reduced treatment modalities have been established for this entity so far. Although the still incomplete and partially inconsistent data in this field needs further study, particular features of HPV-related cancers such as specific microRNA expression, immunology, or gene methylation patterns certainly have the potential to be implemented in future diagnostic and therapeutic concepts.

Introduction: This study reports the oncological outcome of a non-selected series of patients with human papillomavirus(HPV)-positive and -negative oropharyngeal squamous cell carcinoma (OSCC) preferentially managed with upfront surgery. Methods: Consecutive OSCC cases (n = 378) diagnosed from 2000 to 2010 in our department were evaluated for risk factors, HPV association, therapy and overall survival (OS). HPV status was determined by combined DNA and p16 testing, and treatment was defined as the first course of treatment with any kind of surgery (upfront surgery) or primary chemoradiotherapy. OS of HPV-associated and HPV-negative patients was compared using Kaplan-Meier and multivariable Cox regression analyses. Results: The majority of OSCC patients (215 of 361; 69.5%) received upfront surgery as first-line treatment in curative intent. The 5-year OS rate in patients with HPV-positive and HPV-negative tumors were 81.1 and 39.7%, respectively. Upfront surgery in HPV-negative (p < 0.001) and HPV-positive patients (p = 0.05) resulted in improved OS only in advanced stages. Multivariate analysis for patients revealed age in HPV-associated OSCC as an independent predictor for improved survival, and age, performance, N status and therapy as independent predictors in HPV-negative OSCC. Conclusions: Non-selected OSCC patients amenable to curative therapy show poor 5-year OS. The benefit of upfront surgery remains unclear. A younger patient age was the main factor for a better outcome in patients with HPV-associated OSCC.

Our nomograms are reliable prognostic methods in patients with OPSCC. Combining HPV DNA and p16 is essential for correct prognostication. The nomograms are available at www.orograms.org .