Abstract. Background: Human papillomavirus (HPV) is a favourable prognostic factor in oropharyngeal cancer. Moreover, we and others reported that HPV-positive cancer of unknown primary in the head and neck region (HNCUP) has better outcome than HPVHead and neck squamous cell carcinoma (HNSCC), including cancer of the pharynx, larynx, oral cavity, nose and nasal sinuses, often presents as a lump in the neck, and the specific site of the primary tumour is in general revealed after subsequent diagnostic procedures. However, in 2-9% of the cases the primary tumour is not found and the condition is denoted as cancer of unknown primary in the head and neck region (HNCUP) (1). Treatment of the latter has traditionally comprised of neck dissection followed by postoperative oncological treatment, i.e. radiotherapy, at times with the addition of platinum-based chemotherapy or cetuximab, while today in some cases only oncological treatment is given (2).Human papillomavirus (HPV)-associated oropharyngeal SCC is a HNSCC subset dominated by tonsillar and base of tongue SCC (3, 4). HPV-positive tonsillar and base of tongue SCC have increased in incidence in the past decades in the developed world and have better clinical outcomes than HNSCC in general [~80% vs. 40% 5-year overall survival (OS)] (5-8). HPV is frequently found in HNCUP and such cases likely have an HPV-positive oropharyngeal SCC origin, which gives reasons for steering diagnostic procedures as well as radiotherapy towards the oropharynx (9-11).Treatment de-escalation may be attainable in patients with HPV-positive HNCUP, similar to that discussed for patients with HPV-positive oropharyngeal SCC (12). Still, before HPV status of HNCUP can be used to guide treatment, more knowledge on the biology and clinical behaviour of the 665 Τhis article is freely accessible online.

Long-term survival data in relation to sub-sites, human papillomavirus (HPV), and p16INK4a (p16) for patients with oropharyngeal squamous cell carcinoma (OPSCC) is still sparse. Furthermore, reports have indicated atypical and late recurrences for patients with HPV and p16 positive OPSCC. Therefore, we assessed long-term survival and recurrence in relation to oropharyngeal subsite and HPV/p16 status. A total of 529 patients with OPSCC, diagnosed in the period 2000–2010, with known HPVDNA and p16-status, were included. HPV/p16 status and sub-sites were correlated to disease-free and overall survival (DFS and OS respectively). The overexpression of p16 (p16+) is associated with significantly better long-term OS and DFS in tonsillar and base of tongue carcinomas (TSCC/BOTSCC), but not in patients with other OPSCC. Patients with HPVDNA+/p16+ TSCC/BOTSCC presented better OS and DFS compared to those with HPVDNA−/p16− tumors, while those with HPVDNA−/p16+ cancer had an intermediate survival. Late recurrences were rare, and significantly more frequent in patients with p16− tumors, while the prognosis after relapse was poor independent of HPVDNA+/−/p16+/− status. In conclusion, patients with p16+ OPSCC do not have more late recurrences than p16−, and a clear prognostic value of p16+ was only observed in TSCC/BOTSCC. Finally, the combination of HPVDNA and p16 provided superior prognostic information compared to p16 alone in TSCC/BOTSCC.

Background: TNM-8 staging separates oropharyngeal squamous cell carcinomas (OPSCC) into human papillomavirus (HPV)-mediated and-unrelated OPSCC based on p16INK4a overexpression (p16þ), as surrogate marker for HPV. However, OPSCC is histologically and clinically heterogenous including tonsillar and base of tongue squamous cell carcinomas (TSCC and BOTSCC respectively), and carcinomas of soft palate and walls (otherOPSCC). The significance of HPV is established in TSCC/BOTSCC, while its role in otherOPSCC is unclear, which is not considered in TNM-8. Here, p16þ was therefore evaluated in relation to overall survival (OS) and tumor stage per OPSCC subsite. Patients and methods: All 932 patients, treated with curative intent in Stockholm 2000e2016 with OPSCC, previously analyzed for p16 expression, were included. Clinical data, including stage and OS, was collected retrospectively. Results: Patients with p16þ otherOPSCC had significantly poorer OS compared to patients with p16þ TSCC/BOTSCC (p Z 0.005) and their survival was similar to that of patients with p16-otherOPSCC/TSCC/BOTSCC. Moreover, patients with TNM-8 stage I-II and p16þ otherOPSCC had a significant poorer OS compared to patients with p16þ TSCC/BOTSCC

HPV16 DNA detection in fine-needle aspirations from neck masses is reliable and HPV16 DNA in a metastasis is a strong indicator of an HPV-positive oropharyngeal SCC. © 2016 Wiley Periodicals, Inc. Head Neck 39: 419-426, 2017.