Human papillomavirus 16 is an aetiological factor of scrotal cancer

Br J Cancer. 2017 Apr 25;116(9):1218-1222. doi: 10.1038/bjc.2017.74. Epub 2017 Apr 4.


Background: Squamous cell scrotal carcinoma (SCSC) is an infrequent skin cancer associated historically with occupational carcinogens. Human papillomavirus (HPV) DNA has been associated with SCSC but there is no definitive proof of its oncogenic role.

Methods: Human papillomavirus-DNA and -E6*I mRNA were analysed in six invasive histologically typed SCSC. LCM-PCR was used to localise HPV DNA to tumour cells. P16INK4aand p53 expression were studied by immunohistochemistry.

Results: In three warty or basaloid SCSC HPV16-DNA and E6*I-mRNA were detected. LCM-PCR confirmed HPV16 was in p16INK4a-positive malignant cells. However, of three usual-type SCSC, all were HPV-negative and two expressed p53 protein but not p16INK4a.

Conclusions: Human papillomavirus 16 was present in tumour cells and oncogenically active in basaloid and warty SCSC, whereas usual SCSC was HPV-negative and showed immunostaining, suggesting p53 mutation. The dual pathways of oncogenesis and relation between histological type of SCSC and HPV are similar to that in penile cancers.

MeSH terms

  • Adult
  • Aged
  • Carcinoma, Squamous Cell / diagnosis
  • Carcinoma, Squamous Cell / genetics
  • Carcinoma, Squamous Cell / pathology
  • Carcinoma, Squamous Cell / virology*
  • Cyclin-Dependent Kinase Inhibitor p16 / biosynthesis*
  • Cyclin-Dependent Kinase Inhibitor p16 / genetics
  • DNA, Viral / isolation & purification
  • Gene Expression Regulation, Neoplastic
  • Human papillomavirus 16 / genetics
  • Human papillomavirus 16 / isolation & purification*
  • Human papillomavirus 16 / pathogenicity
  • Humans
  • Male
  • Middle Aged
  • Mutation
  • Oncogene Proteins, Viral / biosynthesis*
  • Oncogene Proteins, Viral / genetics
  • Papillomavirus Infections / diagnosis
  • Papillomavirus Infections / virology
  • Penile Neoplasms / diagnosis
  • Penile Neoplasms / genetics
  • Penile Neoplasms / pathology
  • Penile Neoplasms / virology*
  • Repressor Proteins / biosynthesis*
  • Repressor Proteins / genetics
  • Tumor Suppressor Protein p53 / biosynthesis*
  • Tumor Suppressor Protein p53 / genetics


  • Cyclin-Dependent Kinase Inhibitor p16
  • DNA, Viral
  • E6 protein, Human papillomavirus type 16
  • Oncogene Proteins, Viral
  • Repressor Proteins
  • TP53 protein, human
  • Tumor Suppressor Protein p53