Programme

Head and neck squamous cell carcinomas (HNSCC) develops in the mucosal lining of the upper aerodigestive tract. The tumours are generally preceded by precancerous changes in the mucosal epithelium. Some of these are macroscopically visible as lesions, but most can only be identified in surgical margins by microscopic examination for dysplasia or by genetic analysis. As these mucosal changes are often not macroscopically visible, they may stay behind untreated and cause recurrent disease.

Since two decades it became recognized that human papillomavirus infection causes a separate subgroup of oropharyngeal cancers. These tumours have a more favourable prognosis and during subsequent years it became apparent that one of the reasons for this favourable prognosis was the lack of precancerous fields preceding the carcinomas. This is highly remarkable as in cervical carcinogenesis, these HPV-mediated tumours are preceded by mucosal lesions that can be visualized using acetic acid, and are the main target of the population-based screening programs for cervical cancer.

Most information on HPV-mediated carcinogenesis has been obtained from cervical cancer research, and remarkable similarities between the putative target cells for malignant transformation, have been found. The lack of HPV-associated precancerous changes in the upper-aerodigestive tract, however, remains an enigma. In this presentation the various aspects of HPV-mediated carcinogenesis will be addressed, including a model and some novel insights.

Clinical Presentation and Outcome of HPV-positive Nasopharyngeal Carcinoma in a North American Cohort; Shao Hui Huang

Single cell RNA Sequencing allows mapping of HPV transcripts in head and neck cancer epithelial cells; Cornelius Kürten

Awareness of HPV-associated oropharyngeal cancer among the general population and general practitioners in The Netherlands: cross-sectional study; Femke Verhees

HPV16 sequence variants and prognosis in HPV-positive OPSCC; Irene Nauta

Combination immunotherapy of cancers caused by high risk HPV16
Anna-Sophia Wiekmeijer, Isa Pharmaceuticals

Therapeutic DNA-enabled Immunotherapies for the treatment of HPV diseases
Jeffrey Skolnik, Senior Vice President of Clinical Development, Inovio

Arenaviral Vectors Impacting HPV16+ HNSC
Klaus Orlinger and Corrine Iacobucci, Hookipa Biotech GmbH

The course of health-related quality of life from diagnosis to two years follow-up in patients with oropharyngeal cancer: does HPV status matter? Laura H.A. Korsten

Ninety-day Mortality following TORS or Definitive Radiotherapy for Oropharyngeal Cancer at American Commission on Cancer-Accredited Facilities; James Bates

Detection and Monitoring of Circulating Tumor HPV DNA in HPV-Associated Sinonasal and Nasopharyngeal Cancers; Daniel Faden

Differences between HPV positive and HPV negative oropharyngeal cancer detected by Non-Gaussian IVIM; Iris Lauwers

Loss of LRP1B expression drives chemo and radiation resistance in HPV-positive head and neck cancer; Mushfiq Shaikh

Proximity ligation-based sequencing for mapping viral integration sites in human papillomavirus positive head and neck squamous cell carcinomas; Imke Demers

HPV16+ OPSCC patients display an overall longer survival and a lower recurrence rate after standard of care treatment than HPV- patients.  Because the composition of the tumor immune microenvironment (TIME) associated with good prognosis generally also predicts the success of immunotherapy, we started  to analyze an unique prospective cohort of HPV- and HPV+  OPSCC patients. We found that clinical outcome is strongly linked to the presence of HPV-specific CD4+ and CD8+ tumor infiltrating lymphocytes (TIL) during >10 years follow-up. New evidence, suggests that immunity is not only targeted at the E6 and E oncoproteins but may also involve the E2 protein. Subsequently, we performed a comprehensive multimodal, high-dimensional strategy to dissect the TIME of treatment-naïve IR+ and IR− OPSCC tissue, including bulk RNA sequencing, imaging mass cytometry and combined single-cell gene expression profiling and T-cell receptor of TIL. This revealed that IR+ tumors expressed higher levels of genes strongly related to interferon gamma signaling, T-cell activation, TCR-signaling, and mononuclear cell differentiation, as well as several immune signaling pathways, than IR− patients, specifically related to ectopic lymphoid structure development. Moreover, scRNAseq identified a subset of clonally expanded CD8+ T cells, dominantly present in IR+ tumors, which secreted T-cell and DC-attracting chemokines. Immune cell infiltration in IR+ tumors is stronger, highly coordinated, and has a distinct spatial phenotypical signature characterized by intra-tumoral microaggregates of CD8+CD103+ and CD4+ T-cells with DCs. In contrast, the IR− TIME comprised spatial interactions between lymphocytes and various immunosuppressive myeloid cell populations, which differed per patient. The impact of these results are discussed in view of our previous and current trials with (combinations of) therapeutic vaccination and checkpoint strategies.

Role of the PuraBond haemostatic agent in Trans oral Robotic surgery – A case series; Mriganka De

Early detection of recurrent HPV-positive HNSCC by ctDNA analysis; Annouk Pierik

Deciphering Knowledge and Opinions of HPV and HPV Vaccination for Facilitation of Point-of-Care Vaccination; Daniel Faden

Nodal involvement determines the initial quantity of circulating free HPV16 DNA in patients with HPV-related oropharyngeal cancer; Tomasz Rutkowski

The tumor immune microenvironment of HPV-negative and HPV-positive oropharynx squamous cell carcinomas; Tara Muijlwijk

5-slide Pitch Hans Berkhof: Preventive vaccination, also in treated OPSCC patients?
5-slide Pitch Tim Waterboer: HPV serology for screening
5-slide Pitch Ingeborg Tinhofer-Keilholz: HPV DNA assays for screening
5-slide Pitch Carole Fakhry: Positively screened for HPV: which intervention?