[Update on HPV-associated head and neck cancer-highlights from the 2019 ASCO Annual Meeting]. / Update zu HPV-assoziierten Kopf-Hals-Karzinomen ­ Highlights der ASCO-Jahrestagung 2019.

At this year's Annual Meeting of the American Society for Clinical Oncology (ASCO), the keyword search "HPV-associated head and neck cancer" resulted in 920 hits-74% of the hits on human papillomavirus (HPV). This underlines the relevance of the topic. The spectrum ranged from validation and separation of the prognostic groups of patients with HPV-associated oropharyngeal carcinoma (OPSCC) according to TNM 8, to the characterization of new tumor markers and tumor mutational burden for possible de-escalation strategies to avoid toxicity of standard multimodal treatments. It has been shown that the separation of p16-positive OPSCC into Union for International Cancer Control (UICC) stages I and II with the current TNM 8 classification without further markers is not sufficiently successful to justify de-escalation strategies. Following publication of the results of the De-ESCALaTE- and RTOG-1016 trials in 2018, which confirm the current standard of care for p16-positive OPSCC, no further phase III studies on de-escalation were presented. In a presented prospective phase II study (NCT02281955), the radiotherapy dose was reduced to cumulative 60 Gy, whereby the simultaneous chemotherapy regimen with cisplatin 30 mg/m2 weekly is not standard of care and could be administered as an alternative to cisplatin cetuximab. Some work dealt with the oral and intestinal microbiota as prognostic markers or their treatment-related changes, particularly under immunotherapy. Modification seems to have a positive impact on the success of therapy. However, robust data are still lacking for the various modified treatments for HPV-associated OPSCC, which are needed before their implementation in daily practice.

[Immunotherapy for head and neck cancer : Highlights of the 2019 ASCO Annual Meeting]. / Immuntherapie von Kopf-Hals-Tumoren : Highlights der ASCO-Jahrestagung 2019.

BACKGROUND: In the field of immunotherapy of head and neck squamous cell carcinoma (HNSCC), a high level of study activity can still be observed. The results of the Keynote-048 study on first-line therapy with pembrolizumab were a highlight at this year's meeting of the American Society of Clinical Oncology (ASCO). MATERIALS AND METHODS: All abstracts and presentations on immunotherapy of head and neck tumors presented at ASCO 2019 were evaluated for relevance and the most interesting studies were summarized. RESULTS: The Keynote-048 study showed an improvement in overall survival with pembrolizumab monotherapy for patients with measurable programmed cell death ligand 1 (PD-L1) expression according to the combined positive score (CPS), and for the whole cohort with the combination of pembrolizumab and platin/5-fluorouracil (FU). The EAGLE study on durvalumab ± tremelimumab in second-line therapy did not demonstrate any improvement in response rates or overall survival compared to standard therapy. In addition, several new immunotherapeutic approaches and combinations were presented. CONCLUSION: The results of the Keynote-048 study have already led to the approval of pembrolizumab in the first line for platin-sensitive HNSCC in the USA and the expected approval in Europe will presumably change the therapeutic landscape in the long term. In the future, effective therapies for patients without a response to programmed cell death 1 (PD-1)/PD-L1 inhibition will be needed.

[Immunotherapy highlights of the ASCO annual meeting 2018 for head and neck cancers]. / Highlights der ASCO Jahrestagung 2018 zur Immuntherapie von Kopf-Hals-Tumoren.

BACKGROUND: Immunotherapeutic strategies are becoming increasingly more important for head and neck cancer and numerous clinical trials were presented at the annual meeting of the American Society of Clinical Oncology (ASCO) 2018. OBJECTIVE: In this review the most interesting clinical trials and trial results for immunotherapy of head and neck cancer are summarized. MATERIAL AND METHODS: All abstracts and presentations on immunotherapy of head and neck cancer at the annual meeting of the ASCO 2018 were screened to select the most interesting trials for a more detailed analysis. RESULTS: For head and neck cancer, practice changing phase III trial results were missing, but several noteworthy new strategies and trial results for immunotherapy were presented. Neoadjuvant immunotherapy trials, results concerning immunotherapy in old age, prognostic implications of immune-mediated adverse events and new immunotherapy combinations are summarized in this article. CONCLUSION: The role of immunotherapy for the treatment of head and neck cancer is markedly increasing. Many pioneering trials are currently ongoing, in the phase of data analysis or in planning.

[HPV-associated oropharyngeal cancer-incidence, trends, diagnosis, and treatment]. / Das HPV-getriebene Oropharynxkarzinom ­ Inzidenz, Trends, Diagnose und Therapie.

A rising incidence of oropharyngeal squamous cell carcinoma (OPSCC) is reported by many countries worldwide and OPSCC associated with human papillomavirus (HPV) has been recently defined as a new class of head and neck cancers. Besides tobacco and alcohol consumption, HPV is an accepted risk and prognostic factor for OPSCC. Although the incidence increase of HPV-associated OPSCC is convincing, cancer registry studies and studies based on cohorts often have drawbacks regarding data linkage to comparable experimental data, comparable anatomical definitions or HPV diagnostics. Patients with HPV-associated OPSCC have remarkably better prognosis and the tumors differ from HPV-negative OPSCC with respect to molecular and genetic aspects. Nevertheless, choice of therapy is independent of HPV, and rather is subject to the individual patient's condition, local preference and anatomic characteristics. New concepts emerge in immune-checkpoint oncology, which might be a valuable add-on to established concepts. Also, treatment de-escalation (e.g., by reduction of radiation dosage) might be suitable for patients with certain risk profiles. Prophylactic vaccination can contribute to reducing HPV-induced disease, likewise OPSCC. Prerequisite is a high rate of vaccination, which is currently not sufficient in Germany. Because of currently low vaccination rates and the rather long time between initial infection and HPV-induced carcinogenesis, reduction of incidence increase or prevalence of HPV-associated OPSCC is not expected in the near future.

[Update on HPV-associated head and neck cancer-highlights of the 2018 ASCO Annual Meeting]. / Update zu HPV-assoziierten Kopf-Hals-Karzinomen ­ Highlights der ASCO-Jahrestagung 2018.

Rising incidence rates in human papillomavirus (HPV)-associated oropharyngeal squamous cell carcinoma (OPSCC) and a significantly improved prognosis have brought this entity into scientific focus. At this year's American Society of Clinical Oncology (ASCO) Annual Meeting, 291 studies with the keyword "HPV" were presented, the majority of which were in head and neck cancer. Due to high rates of late toxicities after conventional therapy, de-intensified treatment concepts are being increasingly discussed, although data from prospective phase III studies were not presented. Retrospective data on the latest TNM staging (downstaging in many HPV-associated patients) and other risk stratification systems were presented. HPV diagnostics based solely on p16 immunohistochemistry were discussed. Many groups presented work on the HPV association and its prognostic relevance not only in oropharyngeal carcinoma, but also in oral cavity, hypopharyngeal, and locally advanced laryngeal squamous cell carcinoma. New prognostic biomarkers such as methylation signatures appear to be promising. New data suggest equal survival rates in HPV-associated stage I OPSCC treated with surgery alone in comparison to patients who received adjuvant therapy after surgery. A possible negative effect on overall survival in stage III HPV-associated OPSCC with a cisplatin dose ≤200 mg/m2 was discussed. Results of de-escalation studies are urgently awaited, in order to be able to treat HPV-associated OPSCC patients as precisely and as specifically as possible and ensure long-term quality of life.

[Human papillomavirus and squamous cell cancer of the head and neck region : Prognostic, therapeutic and prophylactic implications]. / Humane Papillomviren bei Plattenepithelkarzinomen der Kopf- und Halsregion : Relevanz für Prognose, Therapie und Prophylaxe.

Human papilloma viruses (HPV) are responsible for approximately half of all oropharyngeal squamous cell carcinomas (OPSCC) and incidence rates of HPV-associated OPSCC continue to increase substantially. The defined viral carcinogenesis permits development of specific diagnostic, therapeutic, and prophylactic approaches. Laboratory identification of HPV-associated OPSCC may be achieved by p16(INK4a) immunohistochemistry combined with HPV DNA detection by polymerase chain reaction (PCR) using tumor tissue. Patients with HPV-associated OPSCC have a relatively good prognosis; therefore, the HPV status plays an important role in patient guidance. Due to the relatively favorable prognosis, ongoing studies are evaluating whether less rigorous therapy for HPV-positive patients results in equally good cure rates. The criteria for patient selection are, however, still uncertain. Particularly markers for detection of HPV-positive patients with a high risk of treatment failure are lacking. Besides tumor stage and comorbidities, distinct genomic, epigenetic, and immunologic alterations are prognostically relevant for HPV-associated OPSCC, and might be of predictive value. Furthermore, the characteristic molecular alterations suggest the possibility of novel vigilant and specific therapy approaches. These may be inhibitors of the phosphatidylinositol 3­kinase (PI3K) pathway, which is frequently activated in HPV-associated OPSCC, and immunotherapeutic methods, e. g., therapeutic vaccination. Although prophylactic HPV vaccinations may also prevent development of HPV-associated OPSCC, foreseeable effects on OPSCC incidence will be low, given the low vaccination rates in Germany. This highlights the fact that interdisciplinary research networks should enhance the necessary activities related to HPV-associated OPSCC.

[HPV-associated head and neck cancer : mutational signature and genomic aberrations]. / HPV-assoziierte Kopf­Hals­Karzinome : Mutationssignaturen und genomische Aberrationen.

A significantly increasing proportion of oropharyngeal head and neck carcinomas (OSCC) in North America and Europe are associated with human papillomavirus (HPV) infections. HPV-related OSCC is regarded as a distinct tumor type with regard to its cellular, biologic, and clinical characteristics. Patients with HPV-related OSCC have significantly better local control, but higher rates of regional lymph node and distant metastases as compared to patients with HPV-negative OSCC. Classical molecular genetic investigations demonstrated specific chromosomal aberration signatures in HPV-related OSCC, and recent developments in next generation sequencing (NGS) technology have rendered possible the sequencing of entire genomes, and thus detection of specific mutations, in just a few days. Initial data from The Cancer Genome Atlas (TCGA) project obtained by using genome-wide high throughput methods have confirmed that HPV-related OSCC contain fewer, albeit more specific mutations than HPV-negative tumors. Additionally, these data revealed the presence of specific-potentially therapeutically targetable-activating driver mutations in subgroups of HPV-positive OSCC, some of which have a prognostic impact. Specific targeted NGS technologies provide new possibilities for identification of diagnostic, prognostic, and predictive biomarkers and the development of personalized cancer treatment. Patients with HPV-positive tumors are likely to profit from these developments in the future, since the genetic alterations are relatively homogenous and frequently lead to signal pathway activation. There is an urgent need for network research activities to carry out the necessary basic research in prospective cohort studies.