We have shown a high frequency (48%) of reduced p16 expression in HNSCC. The reported frequencies of negative expression (the definitions of negative expression were not mentioned in the reports) of p16 in HNSCC were 83% in 29 tumours (sites not mentioned) by Reed and colleagues9
and 67% in 27 maxillofacial squamous cell carcinomas by Zhao et al
However, the clinicopathological significance was not analysed in these two previous reports. Because we were interested to know the clinicopathological significance in relation to surgical management, we excluded patients without surgical treatment.
p16 expression was not significantly related to sex, age of patients, or grade of tumours. However, decreased expression of p16 was found more frequently in carcinomas of the larynx compared with the pharynx (the oropharynx and hypopharynx had similar incidences) and the oral cavity. There are significant differences in the clinical features, risk of nodal metastasis, and prognosis for squamous cell carcinoma of the oral cavity, pharynx, and larynx, despite their similar histological features.12–17
Different p16 expression patterns in distinct sites in the head and neck region may be one of the genetic abnormalities that have contributed to their differences in clinical behaviour.
Weak expression of p16 was also found more frequently in advanced T stages. In HNSCC, the larger the tumour size, the higher the T stage. Because the p16 protein is an important cell cycle regulatory protein, the underexpression of this protein will allow cancer cells to proliferate without control. In HNSCC, it might indicate that weak expression of p16 contributes to a more proliferative cancer behaviour so that tumours with weak p16 expression would tend to be of a larger size and higher T stage.
The most common treatment failure in HNSCC is nodal metastasis.12–16
Although downregulation of p16 expression contributed significantly to tumour proliferation and tumour size, it did not significantly affect nodal metastasis. p16 gene expression is unrelated to metastasis phenotype. However, p16 expression in HNSCC had no prognostic significance for survival in patients who were treated by surgery. The result of prognosis of surgical patients cannot be projected for those patients who are treated by primary radiotherapy and or chemotherapy.
In conclusion, downregulation of p16 expression was seen frequently in HNSCC. Tumours of the larynx, pharynx, and oral cavity had significantly different incidences of decreased expression of p16. Downregulation of p16 significantly contributed to cellular proliferation and tumour size. However, it has no prognostic significance for nodal metastasis and survival.