Quantitative analysis of radiation-associated cellular changes in oral cancer and their correlations with histologic grade and clinical stage: a multivariate evaluation of 43 patients.

Objective: To quantitate radiation-associated cytologic abnormalities in oral cancer cells and analyze their relationships with radiation dose, clinical stage and histologic grade.

Study Design: Forty-three oral cancer patients receiving 2 Gy of fractionated radiotherapy per day were enrolled. Scrape smears were taken from the tumor surface before treatment and serially after 6-, 12-, 18- and 24-Gy fractions. Counts were done after Giemsa staining for the number of tumor cells; micronucleated, nuclear budded, binucleated and multinucleated tumor cells; cells with abnormal nuclear chromatin and membrane; cells with cytoplasmic granulation and vacuolization; and histiocytic giant cells. The variation in these counts with increasing radiation dose was assessed and compared with the histologic grade and clinical stage.

Results: Before therapy, counts for 7 of 10 cytologic abnormalities were significantly different between the 3 histologic grades (Kruskal-Wallis test). With increasing radiation dose, only micronucleation and nuclear budding remained significantly different within the grades. Most cytologic features were not significantly different in early and advanced clinical stage cancers before or after irradiation (Mann-Whitney U test).

Conclusion: Cellular changes do not show a relationship with clinical stage either before or after irradiation. However, they demonstrate a partial pretherapy correlation with histology. This relationship diminishes progressively with increasing radiation dose. Since micronucleation and nuclear budding remain significantly different between histologic grades even after 24 Gy of irradiation, they may be utilized as clinically practicable alternatives to biopsy at this stage and may be useful in further studies on cytologic prognostication of irradiated oral cancer.