Factors of importance for radiosensitivity of tonsillar carcinoma

Radiotherapy (RT) alone or in combination with surgery is the only curative treatment of tonsillar carcinoma (TC). As distant metastases are rare the loco-regional control is the most important factor determining survival. Methods for prediction of radiocurability are lacking. Finding biological markers for predicting the outcome of RT in TC may offer the possibility to customise radiotherapy aiming to decrease the RT-related morbidity and to increase local control and survival.

Human papilloma virus (HPV) is frequently found in TC and may influence response to RT and prognosis. Since HPV may abrogate the function of P53 and since P53 may influence radiosensitivity (RS), it is important to investigate how HPV infection and P53 may influence RT outcome and survival. Proteins involved in detection and repair of DNA damage such as the DNA-PK complex may also have a potential in predicting RT outcome. The aim of this thesis is to investigate HPV, P53 and its negative regulator MDM2 and the components of the DNA-PK complex: DNA-PKcs, Ku86, Ku70 as molecular factors which may predict RT outcome and possibly be used as prognostic factors in TC. An analysis of patients with TC receiving RT at Radiumhemmet 19801995 showed that complete remission (CR) after RT predicted for long term survival. In a subset of these patients, HPV positivity was found to predict for improved survival and diminished risk for tumour relapse.

Tumours expressing high levels of Ku86 had better loco-regional control in contrast to tumours expressing low levels of Ku86. Thus, Ku86 may be used as a predictive factor for radiotherapy outcome in patients with tonsillar carcinoma. High expression of DNA-PKcs is prognostic for better survival when compared to low expression of DNA-PKcs. The prognostic strength of DNA-PKcs expression by IHC may increase if it is analysed together with P53 or MDM2.

List of scientific papers

I. Friesland S, Fernberg JO, Lundell G, Munck-Wikland E, Strander H, Lewensohn R (1999). Prognostic impact of complete remission after preoperative irradiation of tonsillar carcinoma: a retrospective analysis of the radiumhemmet data, 1980-1995. Int J Radiat Oncol Biol Phys. 45(5): 1259-66.
https://pubmed.ncbi.nlm.nih.gov/10613321

II. Mellin H, Friesland S, Lewensohn R, Dalianis T, Munck-Wikland E (2000). Human papillomavirus (HPV) DNA in tonsillar cancer: clinical correlates, risk of relapse, and survival. Int J Cancer. 89(3): 300-4.
https://pubmed.ncbi.nlm.nih.gov/10861508

III. Friesland S, Mellin H, Munck-Wikland E, Nilsson A, Lindholm J, Dalianis T, Lewensohn R (2001). Human papilloma virus (HPV) and p53 immunostaining in advanced tonsillar carcinoma--relation to radiotherapy response and survival. Anticancer Res. 21(1B): 529-34.
https://pubmed.ncbi.nlm.nih.gov/11299799

IV. Friesland S, Kanter-Lewensohn L, Munck-Wikland E, Tell R, Lewensohn R, Nilsson A (2002). Expression of Ku86 confers favourable outcome of tonsillar carcinoma treated with radiotherapy. [Submitted]