E6/E7 expression of human papillomavirus types in cutaneous squamous cell dysplasia and carcinoma in immunosuppressed organ transplant recipients.
BACKGROUND
DNA of cutaneous human papillomavirus (HPV) types is frequently found in nonmelanoma skin cancer, and their E6 and E7 proteins can have transforming properties.


OBJECTIVE
To assess the biological activity of HPV types found in tumour tissues we examined HPV E6/E7 RNA expression and the antibody response to E6, E7 and L1 proteins.


METHODS
Thirty-one snap-frozen biopsies from six immunosuppressed organ transplant recipients representing seven squamous cell carcinomas (SCCs), one basal cell carcinoma, four actinic keratoses (AKs), seven normal skin and 12 verrucae vulgaris (Vv) were analysed for 24 cutaneous HPV types by an L1 DNA polymerase chain reaction (PCR)-based method. The presence of E6/E7 transcripts of HPV 5, 8, 9, 15 and 20 was investigated by real-time reverse transcription-PCR. HPV DNA load was determined for HPV 8, 9 and 15 in 11 biopsies. Antibody response was measured by enzyme-linked immunosorbent assay using affinity-purified, bacterially expressed complete viral proteins fused to glutathione S-transferase as antigens.


RESULTS
HPV DNA was detected in 25 of 31 tissue samples, indicating eight single and 17 multiple HPV infections. E6/E7 transcripts of HPV 8, 9 and 15 were found in low copy numbers in one SCC and three AKs, but not in normal skin or Vv. All four patients examined showed antibodies to cutaneous HPV antigens, but the antibody response did not correlate with E6/E7 expression detected in the tumour.


CONCLUSIONS
Transcriptional activity of the E6/E7 oncogenes in AK and SCC suggests an active role of HPV in the lesion.
Dang
C
C
Department of Dermatology, Charité, Skin Cancer Center Charité, University Hospital of Berlin, Charitéplatz 1, D-10117 Berlin, Germany.
Koehler
A
A
Forschner
T
T
Sehr
P
P
Michael
K
K
Pawlita
M
M
Stockfleth
E
E
Nindl
I
I
D000914:Antibodies, Viral / Q000097:blood; D036022:Capsid Proteins / Q000235:genetics; D002294:Carcinoma, Squamous Cell / Q000276:immunology / Q000821:virology*; D004279:DNA, Viral / Q000032:analysis; D004268:DNA-Binding Proteins / Q000235:genetics*; D006801:Humans; D016867:Immunocompromised Host; D009856:Oncogene Proteins, Viral / Q000235:genetics*; D016377:Organ Transplantation; D050725:Papillomavirus E7 Proteins / Q000235:genetics* / Q000276:immunology; D012367:RNA, Viral / Q000032:analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012867:Skin / Q000276:immunology / Q000473:pathology / Q000821:virology; D012878:Skin Neoplasms / Q000276:immunology / Q000821:virology*; D019562:Viral Load
D000914:Antibodies, Viral; D036022:Capsid Proteins; D004279:DNA, Viral; D004268:DNA-Binding Proteins; C466081:E6 protein, Human papillomavirus type 8; C487708:E6 protein, human papillomavirus type 5; C114580:HPV L1 protein, Human papillomavirus; D009856:Oncogene Proteins, Viral; D050725:Papillomavirus E7 Proteins; D012367:RNA, Viral