Klinisk institutt 1

Midtveisevaluering - Borghild Ljøkjel

Midtveisevaluering for ph.d.-graden ved Universitetet i Bergen for kandidat Borghild Ljøkjel

Borghild Ljøkjel er tilknyttet Klinisk institutt 1. Veiledere er Hans Jørgen Aarstad, Lars Helgeland og Stein Lybak.


The clinical relevance of being HPV infected as Head and Neck Squamous Cell Carcinoma patient


In 2008, there were approximately 630 000 new cases of cancers of the lip, oral cavity, pharynx and larynx reported worldwide, making head and neck cancer (HNC) the sixth most common cancer worldwide. In Norway, the prognosis has improved somewhat the last years, but still only 65% of HNSCC patients survive 5 year. There is a major surge to improve the treatment modalities of this disease. Although smoking has decreased markedly in the population, the incidence of cancer, especially in the tonsils and base of tongue, has increased steeply during the last two decades. In recent years it has been clear that Human Papilloma Virus (HPV) is linked to development of oropharynx squamous cell carcinoma (OPSCC). We, and others, have found an increased incidence of OPSCC probably due to HPV infection.

Haukeland University Hospital (HUH) treats all cases of head and neck cancer (HNC) in the Western Health Care region of Norway, which has approximately one million inhabitants. Since 1992, all patients diagnosed with HNC at the Department of Otolaryngology/ Head and Neck Surgery, HUH, have been registered in a hospital-based HNC registry. From this current databank we have extracted the patients with oropharyngeal cancer in the period 1992-2008. We have determined HPV status of these patients tumors by PCR method.

In our study we have showed that the incidence of HPV-positive OPSCC increased form 0,34 in the period 1993-1998 to 1,0 in 2002-2007, while the numbers of HPV-negative patients remained constant. We also showed that the survival was better among HPV-positive patients compared to HPV-negative patients.

For this population of OPSCC in Western Norway we have also found that TNM score predicted survival only among HPV-negative patients. A previous history of smoking and age predicted DSS among HPV-positive patients whereas operability at diagnosis predicted DSS among both HPV-positive and HPV-negative patients.

We have also published a paper which shows that primary surgery gives no  survival benefit compared to primary radiation for these oropharyngeal cancer patients treated in Western Norway.

We have recently studied macrophage and T lymphocytes infiltration in OPSCC tumors. We have performed immuno-histo-chemistry analyses studying tumor density of CD68, CD3 and FoxP3 positive cells. We are no analyzing these data. Preliminary results shows that macrophage (CD68), total T lymohocytes and T regulatory (FoxP3) epithelial tumor infiltration levels predict five-year disease-specific survival of OPSCC patients. Macrophage infiltration level predicted in particular survival among HPV negative patients, whereas T regulatory cell levels predicted survival among both HPV negative and positive patients.

Hopefully, the results will contribute to a better understanding of OPSCC biology.