Background: Head and neck cancers are often diagnosed at a late stage, thus resulting in a generally poor prognosis. This is partly attributable to patients’ hesitancy in seeking treatment. However, the length and causes of these patient delays remain relatively unknown. Material and methods: We included all new head and neck cancer patients treated at our tertiary care center between 2016 and 2017. Using a patient questionnaire, we collected data on patients’ symptoms and other factors related to seeking medical care, and recorded both patient- and primary health care-related delays. We then compared the data collected from these patients to patient and tumor characteristics collected from hospital records, and analyzed various causes for delay before a specialist consultation to the Department of Otorhinolaryngology – Head and Neck Surgery. Results: Among the patients (n = 142) in our study, the median patient delay was 35 d with 73% of patients seeking medical care within 3 months. In comparison, the median primary health-care delay was 20 d. Certain symptoms influenced patient delay. Hoarseness and breathing difficulties correlated with longer patient delay while patients with a lump on the neck had a shorter delay. Patient delay was associated with certain tumor-related factors such as the tumor site and the presence of regional metastases, which resulted in shorter patient delay. None of the patient-related factors appeared to impact delay. Important factors influencing primary health-care delay included the initial location visited and whether any follow-up visit was scheduled or not. Conclusions: Although most patients sought medical advice without a major delay and were adequately referred, we found that long delays existed. Raising awareness of the symptoms of head and neck cancer among general population and health-care providers is probably the best way to get patients to curative treatment without delay.

Different Toll-Like Receptor Expression Patterns in Progression toward Cancer

Background: The etiological role of human papillomavirus (HPV) in oropharyngeal squamous cell carcinoma (OPSCC) is confirmed. However, the role of other oncoviruses in OPSCC is unknown. Materials and methods: A total of 158 consecutive OPSCC patients treated with curative intent were included. DNA extracted from tumor sections was used to detect Epstein–Barr virus (EBV), HPV, and the following polyomaviruses: John Cunningham virus (JCV), Simian virus 40 (SV40), and BK virus (BKV) with PCR. In addition, p16 expression was studied by immunohistochemistry, and EBV-encoded small RNA (EBER) transcripts were localized by in situ hybridization. The effect of viral status on overall survival (OS) and disease-free survival (DFS) was analyzed. Results: A total of 94/158 samples (59.5%) were HPV-positive, 29.1% contained BKV DNA, 20.3% EBV DNA, 13.9% JCV DNA, and 0.6% SV40 DNA. EBER was expressed only in stromal lymphocytes adjacent to the tumor and correlated with HPV positivity (p = 0.026). p16 expression associated only with HPV. None of the three polyomaviruses had an impact on survival. Patients with EBER-positive but HPV-negative OPSCC had significantly poorer OS and DFS than those with HPV-positive OPSCC and slightly worse prognosis compared with the patients with EBER-negative and HPV-negative OPSCC. Conclusion: Polyomaviruses are detectable in OPSCC but seem to have no impact on survival, whereas HPV was the strongest viral prognostic factor. EBER expression, as a sign of latent EBV infection, may have prognostic impact among patients with HPV-negative OPSCC. EBER analysis may identify a new subgroup of OPSCCs unrelated to HPV.

Background An emerging subset of oropharyngeal squamous cell carcinomas (OPSCC) is caused by HPV. HPV-positive OPSCC has a better prognosis than HPV-negative OPSCC, but other prognostic markers for these two different diseases are scarce. Our aim was to evaluate serum levels and tumor expression of matrix metalloproteinase-8 (MMP-8) and tissue inhibitor of metalloproteinase-1 (TIMP-1) and to assess their prognostic role in HPV-positive and HPV-negative OPSCC. Materials and methods A total of 90 consecutive OPSCC patients diagnosed and treated with curative intent at the Helsinki University Hospital between 2012 and 2016 were included. Serum samples were prospectively collected. An immunofluorometric assay and an enzyme-linked immunosorbent assay were used to determine MMP-8 and TIMP-1 serum concentrations, respectively. HPV status of the tumors was determined using a combination of HPV-DNA genotyping and p16-INK4a immunohistochemistry. The endpoints were overall survival (OS) and disease-free survival (DFS). Results High TIMP-1 serum levels were strongly and independently associated with poorer OS (adjusted HR 14.7, 95% CI 1.8–117.4, p = 0.011) and DFS (adjusted HR 8.7, 95% CI 1.3–57.1, p = 0.024) among HPV-negative patients; this association was not observed in HPV-positive OPSCC. Although TIMP-1 was immunoexpressed in the majority of the tumor tissue samples, the level of immunoexpression was not associated with prognosis, nor did MMP-8 serum levels. Conclusion Our results indicate that serum TIMP-1 levels may serve as an independent prognostic marker for HPV-negative OPSCC patients.