Study of multiple human papillomavirus-related lesions of the lower female genital tract by in situ hybridization

Twenty-six women with multiple human papillomavirus (HPV)-related lesions of the lower genital tract were investigated by immunohistochemistry for the internal genus-specific capsid antigen of HPV and by DNA-DNA in situ hybridization with ³⁵S-radiolabeled probes for sequences of HPV- 6 11, HPV-16, and HPV-18. The vulva was the most frequently affected site in all of these cases; the cervix was the second most frequently affected site. The lesions displayed the features of papillomavirus infection in 14 patients, and there was also histologic evidence of early neoplasia in 12 patients. The mean age of patients with and without neoplasia was 40 and 30 years, respectively. Evidence of HPV association was found in 73% of the vulvar lesions and in 40% of the other synchronous lesions by one or both methods. Viral DNA was found in 67% of patients with neoplasia and in 71% of patients without neoplasia. Eleven of 12 HPV-positive patients with neoplasia revealed the presence of HPV-16 in their tissues by in situ hybridization. On the other hand, 50% of those without neoplasia had HPV-16 DNA, whereas the presence of HPV- 6 11 was found in the other 50%. The clinical course of the disease, the distribution of HPV type, and the type of antigen in patients with and without neoplasia suggest that progression to neoplasia was associated with HPV-16. These results stress the practical value of the in situ hybridization method for the identification of those patients with HPV infection who are at risk for progression to malignancy.