Methods for early diagnosis of head and neck cancer

Abstract

Head and Neck squamous cell cancer (HNSCC) is the fifth most common malignancy in the western countries and in Sweden it comprises 2- 3% of all cancer cases. Alcohol and tobacco are known as principal etiological factors but other carcinogenic attributes i.e. viruses and bethel chewing have also been recognised. The HNSCC is classified according to the TNM classification and morphologically graded into well, moderately and undifferentiated tumors. Curative treatment implies surgery and/or radiotherapy. Despite therapeutic advances such as chemotherapy concomitant to radiation, intensified radiation regimes and advanced surgical approaches the long term clinical outcome of the patients with HNSCC has not improved significantly in the last decades.

Cancers diagnosed at an early stage have better cure rates than late stage diseases. The aim of this thesis was to elucidate and investigate if laminin-5 and DNA-analysis (aneuploidy) are useful for risk assessment and diagnosis in HNSCC.

Laryngeal cancer in situ (CIS) lesions can progress to invasive cancer and there is no reliable predictor for this. Distinction between CIS and invasive cancer can at times be difficult to asses and hence delay appropriate therapy. In a retrospective study of laryngeal CIS lesions we found that lesions which progressed to invasive cancer during 5-year followup were significantly more often laminin positive than the lesions that did not progress. Various mucosal lesions are frequently encountered in the oral cavity. A marker to identify the truly preneoplastic lesions in order to warrant appropriate treatment and follow-up would be of utter clinical value.

In a retrospective study of dysplastic and reactive lesions which later progressed to cancer or CIS lesions on the same site, we found that 60% of precursor lesions were laminin-5 positive and hereby differed significantly from the matched control lesions that did not progress. Although these investigations are small, our data indicates that laminin-5 expression can help to identify CIS laryngeal lesions with invasive potential and identify oral mucosal lesions at risk for tumor progression.

Distinction between branchial cleft cyst (BCC) and cystic metastases of HNSCC can at times be difficult by cytomorphology. A vast majority of HNSCC exhibit aneuploidy at time of diagnosis. We performed Image cytometry DNA analysis on the fine needle aspiration (FNA) specimens of "BCC"s both in a retrospective and a prospective study. We found that all benign lesions were diploid whereas in the former study 53% of the "BCC"s which later proved to be malignant by histopathology showed aneuploidy.

In the latter study INA from all 14NSCC cystic metastasis which could be assessed showed aneuploidy. Our data suggests that ICM DNA analysis is a valuable supplement when distinction between BCC and cystic metastases of HNSCC is required especially when conventional cytological evaluation is ambiguous.