Morphology, DNA ploidy and HPV in lung cancer and head and neck cancer

Lung cancer and head and neck cancer have similar genotoxic risk factors. While the vast majority of lung cancers are caused by cigarette smoking alone, smoking together with heavy drinking are the major etiological agents of head and neck cancer. In addition, human papilloma virus (HPV) has been identified as an important causative factor of tonsillar carcinomas. In contrast, chromosomal instability and aneuploidy identifiable by DNA measurement are predominately associated with cancer progression. This selective review summarizes our studies that aimed to gain a better understanding of the biology and pathology of lung cancer and head and neck cancer. In particular, it was attempted (a) to develop a microscopy-based tumor classification system that provides insight into the genetics of cancer cells and in particular their DNA ploidy, (b) to apply this classification system to lung cancer and head and neck cancer and to correlate it with clinicopathological parameters and molecular biomarkers, and (c) to analyze molecular characteristics and in particular the presence of human papilloma virus in lung cancer and head and neck cancer. Therefore, we developed a core classification based on the semi-quantitative assessment of the size and type of tumor cell nuclei and mitoses. It was found that (1) nuclear and mitosis size correlated with the DNA content of the tumor cells, (2) tripolar mitoses were indicative of cancer with near-triploid DNA content, (3) morphological and DNA parameters indicating variability of the cancer genome were associated with poor prognosis of lung cancer patients, (4) HPV-positive head and neck squamous cell carcinomas were characterized by smaller tumor nuclei and reduced DNA amount compared to HPV-negative carcinomas, and (5) HPV is associated with lung cancer in certain geographical regions of the world.