Advanced, unresectable squamous cell cancer (SCC) of the Head and Neck (H&N) remains an incurable disease in spite of aggressive surgical and/or radiation therapy. Single and combination chemotherapy has been added to surgery and/or radiation therapy in an attempt to improve this outcome. Impressive cytoreduction has been achieved with cis-platinum containing regimens with overall response rates between 80 and 90% and complete response rates in the range of 50-60% having been reported. In the last six years over 300 such patients have been treated with these regimens at Wayne State University. During these trials both favorable and unfavorable prognostic groups have been identified on the basis of clinical presentation and initial response to chemotherapy. Careful review of these trials has failed to identify clinical or morphological criteria that pretherapeutically recognize or predict these prognostically important subgroups on an individual patient basis. Recently, cellular parameters determined by flow cytometry (FCM) particularly cellular DNA content as defined by DNA index (DI) and percent S phase fraction (SPF), have been reported to correlate with response to chemotherapy, survival and biological behavior in large heterogenous groups of tumors as well as certain individual tumors. This application proposes to investigate the possibility of identifying therapeutically and prognostically important subgroups of SCC of H&N using FCM determined cellular parameters. Such identification would allow the appropriate stratification of clinical trials, the design of more aggressive protocols for poor prognostic groups and the ability to recognize and study the biological differences between these clinical subgroups.