, . 181: 348 (1997) AUTHORS’ REPLY We would like to thank Dr Ogden for his comments. Although little has been published on the expression of CK-16 in head and neck cancer, limited data are available indicating that its expression increases during the carcinogenesis process, as published by van der Velden et al.1 and Morgan et al.2,3 In addition, it was hypothesized that being a marker of hyperproliferation, its expression might reflect increased levels of cell turnover, as can be expected in (pre-)malignant tissue. This marker could then act as a delayed form of other well-known proliferation markers like KI-67 expression. With respect to the occurrence of second primary tumours in relation to marker expression, this question cannot be answered. At this moment, the number of patients with a second primary tumour is too low to allow proper analysis. There is a chance that other risk factors (smoking, age, and variation in duration of follow-up) may play a confounding role. To correct for these other possible risk factors, it may very well be that 25 patients in the starting group is not enough. A further complication is that this group of patients is heterogeneous with respect to the TNM stage. We have already noted that a significant proportion of the patients, mainly those with a relatively high TNM stage, ? 1997 by John Wiley & Sons, Ltd. did not have the chance to experience a second primary tumour because they died of their first tumour. To prove the role of these markers in a definitive setting, we have collected cytological samples of a new group of over 100 patients with only early stage tumours, who will now be followed up for a sufficient period of time to allow this question to be resolved. B. J. M. B G. B. S Department of Otolaryngology Academisch Ziekenhuis Vrije Universiteit P.O. Box 7057 1007 MB Amsterdam The Netherlands REFERENCES 1. 2. 3. van der Velden L-A, Schaafsma HE, Manni JJ, Ramaekers FCS, Kuijpers W. Cytokeratin expression in normal and (pre)malignant head and neck epithelia. Head Neck 1992; 15: 133–146. Morgan PR, Shirlaw PJ, Johnson NW, Leigh IM, Lane EB. Potential applications of anti-keratin antibodies in oral diagnosis. J Oral Pathol 1987; 16: 212–222. Morgan PR, Su L. Intermediate filaments in oral neoplasia. I. Oral cancer and epithelial dysplasia. Oral Oncol Eur J Cancer 1994; 30B: 160–166.