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, 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.