Oropharyngael cancer : changing management and the role of Toll-like receptors

Research output: ThesisDoctoral ThesisCollection of Articles


Head and neck cancers constitute the seventh most common cancer group worldwide. Their incidence has been declining in the Western world, along with the decrease in tobacco smoking. The incidence of oropharyngeal squamous cell carcinoma (OPSCC) has been rising over the last two to three decades in many Western countries. This trend is attributed to human papillomavirus (HPV), which is responsible for the majority of OPSCC cases, whereas, the incidence of HPV-unrelated OPSCC has decreased. HPV-positive OPSCC differs from the HPV-negative form in various aspects: Patients are younger, and they typically have less tobacco and alcohol consumption. They tend to have smaller primary tumors but more advanced disease in the neck. Patients with HPV-positive tumors have better odds of survival, but their post-treatment lifetime may be harmed by major treatment-related morbidity. Many prospective randomized trials delivering de-intensified treatment for this OPSCC patient group are currently ongoing. Validated predictive biomarkers could aid in the treatment individualization of OPSCC. The only well-validated prognostic biomarkers in OPSCC are HPV and protein p16, reflecting HPV involvement. Toll-like receptors (TLRs) are receptors, which initiate immunological cascades. In HPV-associated cervical carcinoma, alteration in the expression of TLRs has been observed. These receptors are also expressed in an altered pattern when HPV infection persists in the cervix. Therefore, these receptors could have a role in HPV-associated OPSCC. The first part of the present study analyzed the treatment and outcome in two patient series treated over a ten-year period. Study I included all OPSCC patients treated at the Finnish university hospitals, and Study II focused on the management of the neck in cN+ disease of patients treated at the Helsinki University Hospital. The cohort included 674 patients, and during the study period, the incidence of this disease increased, which mainly occurred in the group of patients carrying a HPV-associated tumor. The outcome of lateral-wall OPSCC (tonsil) remained similar compared to an earlier Finnish nationwide report, but the outcome of anterior-wall disease (base of tongue) slightly improved. Study II revealed that the relative rate of neck dissections had decreased while the delivery of definitive oncological treatment had increased. However, the regional control rate had not worsened. Regional failures occurred in patients with class cN2b or higher and they often developed on the contralateral side of the neck, including in patients with an ipsilateral primary tumor. The second part of this thesis study (Studies III and IV) evaluated the role of TLRs in OPSCC. As a pilot study, we analyzed TLR 2, 3, 4, 5, 7, and 9 expression, p16 expression, and HPV status in 35 OPSCC samples. TLR 5, 7, and 9 expression varied according to p16 and HPV status. Based on these results, we evaluated the association of TLR 5, 7, and 9 with clinicopathological and outcome data in a cohort of 202 OPSCC patients. The findings indicated that high TLR 5 expression and low TLR 7 expression were related to poor disease-specific survival in the group of HPV-positive OPSCC patients.
Original languageEnglish
  • Atula, Timo Sakari, Supervisor
  • Mäkitie, Antti, Supervisor
  • Hagström, Jaana, Supervisor
Award date9 Mar 2018
Place of PublicationHelsinki
Print ISBNs978-951-51-4049-4
Electronic ISBNs978-951-51-4050-0
Publication statusPublished - 2018
MoE publication typeG5 Doctoral dissertation (article)

Fields of Science

  • 3125 Otorhinolaryngology, ophthalmology
  • 3122 Cancers
  • 3111 Biomedicine

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