HUMAN PAPILLOMAVIRUS INFECTIONS IN NONMELANOMA SKIN CANCERS FROM RENAL-TRANSPLANT RECIPIENTS AND NONIMMUNOSUPPRESSED PATIENTS

Background: Nonmelanoma carcinomas of the skin represent the most freq uent cancers among the Caucasian population worldwide. They occur with high frequency in renal allograft recipient patients after prolonged immunosuppression. Purpose: We analyzed tumors obtained from both immu nosuppressed and nonimmunosuppressed patients for human papillomavirus (HPV) DNA. Methods: Twenty-nine specimens of nonmelanoma carcinomas o f the skin were obtained from 19 renal allograft recipient patients; t hese included 20 specimens of squamous cell carcinoma (SCC) from 11 pa tients, five specimens of basal cell carcinoma (BCC) from four patient s, and four specimens of carcinoma in situ (CIS) from four patients. F orty-one specimens of nonmelanoma carcinomas of the skin were obtained from 32 nonimmunosuppressed patients; these included 26 SCC specimens from 19 patients, 11 BCC specimens from nine patients, and four kerat oacanthoma (benign epithelial tumor) specimens from four patients. A p olymerase chain reaction method involving use of degenerate oligonucle otide primers, in which the conserved region of the open reading frame of the HPV L1 (major capsid protein) gene is amplified, was used to a mplify total cellular DNA purified from individual tumors. The DNA of each specimen was subjected to 16 different amplification reactions; d ifferent primer combinations were used in order to increase the sensit ivity and specificity of HPV detection. Resulting products were probed with a radioactively labeled, degenerate oligonucleotide. HPV-specifi c DNA was either sequenced directly after elution from the gel or ampl ified with semi-nested, degenerate primers, after which the products w ere cloned and sequenced. Sequences were compared with all known papil lomavirus sequences. Results: Thirteen (65%) of the 20 SCC specimens a nd three of the five BCC specimens from immunosuppressed (renal allogr aft recipient) patients contained identifiable HPV-related sequences, among them 13 putative novel HPV genomes. In addition, all other malig nant tumor specimens from this patient group revealed faint signals up on amplification and hybridization; the origin of these signals has no t been identified in the present study. In nonimmunosuppressed patient s, eight (31%) of 26 SCC specimens and four (36%) of 11 BCC specimens contained sequences of HPV types. Two putative novel HPV sequences cou ld be identified in this group. Faint signals of yet undetermined orig in were observed in eight of the SCC specimens and in two of the BCC s pecimens. Two of four keratoacanthoma specimens contained sequences of known HPV type. (Keratoacanthoma is a nonmalignant lesion for which t he natural history has not been defined.) The spectrum of HPV types in both groups of patients differed substantially. Conclusions: These da ta point to the frequent presence of HPV sequences in SCCs and BCCs of the skin. The etiologic relationship of these infections to the respe ctive malignant tumors remains to be evaluated. Implications: The pres ence of HPV DNA in a large percentage of specimens of nonmelanoma carc inomas of the skin from immunosuppressed patients, as well as from non immunosuppressed patients, renders a papillomavirus infection as a pos sible factor in the etiology of this disease.