Human papillomavirus and overexpression of P16INK4a in nonmelanoma skin cancer.
BACKGROUND
P16INK4a overexpression has been identified as a specific biomarker in high-risk human papillomavirus (HPV)-infected cervical (pre)cancer lesions.


OBJECTIVE
To evaluate the overexpression of this cyclin-dependent kinase inhibitor in skin tumors depending on HPV infections, we analyzed normal skin, benign skin disease, and skin cancer specimens.


METHODS
Biopsies of 23 patients with normal histology (3), psoriasis (2), verrucae vulgaris (2), actinic keratoses (5), squamous cell carcinoma (SCC) in situ (3), Bowen's carcinoma (1), and SCC (7) were analyzed. Specimens of 23 patients were immunostained using the monoclonal antibody E6H4 specific for p16INK4a. HPV status was assessed by a polymerase chain reaction (PCR) system to detect all currently known HPV types. MY (MY09/MY11 and MYN9/MYN10)-, CP (CP65/CP70 and CP66/CP69)-nested PCR, and three single PCR methods CN1, CN3, and CN4 were used in a first step, and HPV typing was performed by restriction fragment length polymorphism analysis. Only beta-globin-positive patients were included in this study.


RESULTS
HPV DNA was detected in all actinic keratoses, SCC in situ, Bowen's carcinoma, and SCC, in 50% (one of two) of verrucae vulgaris, in 66% (two of three) of normal skin, and in none of two psoriasis. P16INK4a expression was not detected in normal skin, psoriasis, and verrucae vulgares. Overexpression of p16INK4a was detected in a subset of dysplastic cells (10% to 80%) of all skin (pre)cancer lesions such as actinic keratoses, SCC in situ, Bowen's carcinoma, and SCC infected with HPV independent of sun exposure.


CONCLUSIONS
P16INK4a appears to be overexpressed in a portion of dysplastic cells from actinic keratoses and SCC. Further studies to examine the association of HPV infection and the overexpression of p16INK4a are warranted.
Charité, University of Berlin, Department of Dermatology, Berlin, Germany. ingo.nindl@charite.de
Ingo
I
Nindl
Thomas
T
Meyer
Tobias
T
Schmook
Claas
C
Ulrich
Rüdiger
R
Ridder
Heike
H
Audring
Wolfram
W
Sterry
Eggert
E
Stockfleth
D000368:Aged; D000369:Aged, 80 and over; D015344:DNA Probes, HPV; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D019942:Genes, p16; D006801:Humans; D008297:Male; D008875:Middle Aged; D027383:Papillomaviridae / Q000145:classification; D030361:Papillomavirus Infections / Q000235:genetics*; D012878:Skin Neoplasms / Q000473:pathology* / Q000821:virology*
D015344:DNA Probes, HPV