The expression of key cell cycle markers and presence of human papillomavirus in squamous cell carcinoma of the tonsil

Head Neck. 2004 Jan;26(1):1-9. doi: 10.1002/hed.10335.


Background: Chemical carcinogens induce squamous cell carcinoma (SCC) of the head and neck by targeting the p53 and the retinoblastoma (pRb) pathways. Human papillomavirus (HPV) might have an etiologic role in these cancers at particular sites. Few studies have compared cell cycle protein expression in HPV-positive and HPV-negative tumors in this region.

Methods: Fifty tonsil SCCs were analyzed for HPV by PCR and for expression of cell cycle proteins (p53, pRb, p16(INK4A), p21(CIP1/WAF1), p27(KIP1), and cyclinD1) by immunohistochemistry.

Results: HPV was present in 42%; almost all were type 16. There were statistical associations between HPV positivity and reduced expression of pRb and cyclinD1, overexpression of p16, and younger patient age. Tumor with down-regulated p27 tended to have down-regulated pRb and p21.

Conclusions: HPV-positive tonsil SCCs have distinct molecular pathways. Their association with younger patient age suggests that they are biologically distinct from HPV-negative tumors.

MeSH terms

  • Adult
  • Age Factors
  • Aged
  • Biomarkers, Tumor / metabolism
  • Carcinoma, Squamous Cell / metabolism*
  • Carcinoma, Squamous Cell / virology*
  • Cyclin D1 / metabolism
  • Cyclin-Dependent Kinase Inhibitor p16 / metabolism
  • DNA, Viral / isolation & purification
  • Down-Regulation
  • Female
  • Humans
  • Immunohistochemistry
  • Male
  • Microfilament Proteins / metabolism
  • Middle Aged
  • Muscle Proteins*
  • Papillomaviridae / isolation & purification*
  • Polymerase Chain Reaction
  • Proto-Oncogene Proteins p21(ras) / metabolism
  • Retinoblastoma Protein / metabolism
  • Tonsillar Neoplasms / metabolism*
  • Tonsillar Neoplasms / virology*
  • Up-Regulation


  • Biomarkers, Tumor
  • Cyclin-Dependent Kinase Inhibitor p16
  • DNA, Viral
  • Microfilament Proteins
  • Muscle Proteins
  • Retinoblastoma Protein
  • Tagln protein, mouse
  • Cyclin D1
  • Proto-Oncogene Proteins p21(ras)