Abstract. The aim of this review is to present the current knowledge on the status and significance of human papillomavirus (HPV) in tonsillar cancer. An increase in the incidence of tonsillar cancer has been reported and recent data suggest that this increase is due to an increased proportion of HPV in these tumours. Furthermore, patients with HPV positive cancer have been shown to have a lower risk of relapse and longersurvivalcomparedtopatientswithHPV-negativetonsillar cancer.Tailoringindividualtreatmentintonsillarcancermaybe of importance in order to reduce patient suffering as well as to increase patient survival. Finally, the fact that the presence of HPV-type16E6andE7mRNAhasbeenascertainedintonsillar cancer suggests that HPV-16 indeed is an aetiological factor associated with the disease and that preventive vaccination for this patient group should be discussed. After years of development and anticipation, preventative vaccines against human papillomavirus (HPV) have now reached clinical practice. This has put even more focus on research regarding which types of cancers are associated with HPV infection, which groups of patients should be vaccinated and the possible beneficial effects of such vaccination (1, 2). The main goal of the two presently approved vaccines (Gardasil and Cevarix), both directed against HPV 16 and 18, is to protect against HPV-induced cervical cancer (3-5). In addition, Gardasil also aims to protect against HPV 6 and 11 and the development of genital warts (3). However, the presence of HPV is not only associated with cervical cancer but also with some types of head and neck, anogenital and non-melanoma skin cancer (6-12). In this review, we focus on the presence of HPV in tonsillar cancer and the increasing role of HPV in this tumour type, since this is the type of head and neck cancer where HPV is most commonly found (8). Tonsillar Cancer Tonsillar cancer is the most common oropharyngeal cancer and tumours are mainly squamous cell carcinomas (8-10, 13). Unfortunately, when patients seek counselling for symptoms, such as pain related to swallowing or difficulties in swallowing, the tumour is fairly large, since small tumours do not present similar distress (9). Treatment with curative intent implies surgery and/or radiotherapy and in some cases also chemotherapy (10, 13). Radiotherapy can be given alone, before surgery i.e. preoperatively, or after surgery i.e. postoperatively. The primary goal for all treatment is to be radical, causing as limited functional and cosmetic damage aspossible.Theextentofthesurgerydependsonthesizeof the primary tumour, the presence of metastases to the neck lymph nodes and the response to the given radiotherapy. If a cure cannot be obtained, the patients receive palliative therapy in order to treat pain and discomfort. Patients with stage I-II oropharyngeal cancer have a 5-year survival of around 60-70%, while patients with larger tumours, stage III-IV, have a 5-year survival of around 10- 25%, while overall survival is around 25% (10, 13). Furthermore, despite similar histology and stage, as well as standardised treatment, it is difficult to predict the outcome of any individual case. Recently, several reports describe the incidence of tonsillar cancer as increasing and indicate that patients with HPV-positive tonsillar cancer have a better clinical outcome than those with HPV-negative tonsillar cancer (10, 14-17). 1133 Correspondence to: Professor Tina Dalianis, Department of Oncology-Pathology, Karolinska Institute, Cancer Center Karolinska R8:01, Karolinska Hospital, 171 76 Stockholm, Sweden. Tel: +46 8 51776583, Fax: +46 8 517 76630, e-mail: Tina.Dalianis@ki.se Key Words: Tonsillar cancer, head and neck cancer, HPV, review. ANTICANCER RESEARCH 28:1133-1138(2008) Review Human Papillomavirus Accounts both for Increased Incidence and Better Prognosis in Tonsillar Cancer HANNA DAHLSTRAND, ANDERS NÄSMAN, MIRCEA ROMANITAN, DAVID LINDQUIST, TORBJÖRN RAMQVIST and TINA DALIANIS Department of Oncology-Pathology, Karolinska Institute, Karolinska Hospital, 171 76 Stockholm, Sweden 0250-7005/2008 $2.00+.40