The causal role of human papillomaviruses (HPV) in squamous cell
carcinogenesis of
tonsillar cancers (TSCC) depends on the activity of the viral
oncoproteins E6 and E7, leading to inactivation of the cellular
tumor suppressor p53 and the retinoblastoma gene product pRb. Because of the negative feedback mechanisms, the pRb inactivation causes an increase of the inhibitor of the
cyclin-dependent kinases p16(INK4a). In 39 TSCC specimens, genotyping based on the amplification of HPV
DNA was carried out using PCR by applying HPV type-specific
oligonucleotides. Subsequently, amplicons were hybridised with fluorescence-labeled complementary probes using the Southern blot technology. For HPV E6/E7
mRNA expression, Northern hybridization and RT-PCR were performed, and for
p16(INK4a) detection, immunohistochemistry was performed. With 21/39 (53%) HPV-positives, the detection rate is within the range that can be expected in TSCC. The E6/E7 oncogene
mRNA was detectable in 11 cases, 10 of which showed positive signals after
p16(INK4a) staining. Albeit the small study group was investigated, the correlation of the HPV
DNA status with the
p16(INK4a) expression was of statistical significance (p = 0.02). Kaplan-Meier estimations revealed better survival outcome for patients with HPV-positive
tumors with detectable E6/E7
mRNA and
p16(INK4a) overexpression (p = 0.02, median observation time 29 months). As
mRNA expression tests are not routinely available in many clinical diagnostic laboratories, and based on the high correlation of
p16(INK4a) staining with HPV E6/E7
mRNA expression, in conclusion we suggest for a deeper exploration for the use of
p16(INK4a) as a
surrogate marker with the potential to impact the standard of care of HPV
DNA-positive head and neck
carcinomas.