Both episomal and integrated forms of human papillomavirus type 16 are involved in invasive cervical cancers.

The form of human papillomavirus type 16 (HPV 16)DNA in specimens of invasive cervical cancer was investigated. High molecular, tandem repeats of viral sequences were detected as several distinct bands, using a low concentration (0.5%) agarose gel and a no-cut enzyme (HindIII) for HPV 16. Two-dimensional agarose gel electrophoresis allowed us to differentiate between the episomal multimeric and the integrated forms of viral DNA. All 34 cervical cancer specimens showed the characteristic PstI cleavage pattern of HPV 16 DNA, indicating that a full viral genome was present in these specimens, and 24 specimens (70%) showed only episomal monomeric or multimeric forms without the integrated form of HPV 16 DNA. The remaining 10 specimens (30%) showed integrated multimeric forms of viral DNA, either without the episomal form (8 specimens) or with the concomitant episomal form (2 specimens). In addition, a metastatic tumor in a pelvic lymph node showed only the episomal form of viral DNA, whereas its primary cervical cancer showed both episomal and integrated forms of viral DNA. There was no correlation between the forms of viral DNA and the clinical stages of tumors. The result indicates that both episomal and integrated forms of a complete HPV 16 DNA are involved in invasive cervical cancers.