No confirmed case of human papillomavirus DNA-negative cervical intraepithelial neoplasia grade 3 or invasive primary cancer of the uterine cervix among 511 patients

OBJECTIVE: This study was undertaken to analyze the prevalence and peculiarities of high-grade cervical neoplasias that are not associated with human papillomavirus (HPV) DNA. STUDY DESIGN: Four hundred nineteen women with a first-time diagnosis of cervical intraepithelial neoplasia grade 3 and 92 women with cervical cancer were examined prospectively with a commercially available HPV DNA test. Negative samples were re-tested by polymerase chain reaction (PCR) with general and type-specific primers while the corresponding histology specimens were evaluated by immunohistochemistry. RESULTS: Of the 511 cases examined, 14 were HPV DNA negative on initial analysis. Of these, 7 were found not to be high-grade cervical neoplasia on histologic review, 3 cases were found to contain high-risk HPV types by PCR, and 2 samples were found to be inadequate for analysis. The 2 remaining HPV-negative cases were FIGO stage III and IV tumors. Immunohistochemistry was consistent with a primary adenocarcinoma of the ovary in 1 case and a primary bladder tumor in the other, although a primary cancer of the cervix could not be ruled out completely. CONCLUSION: After exclusion of inadequate samples and erroneous diagnoses, HPV DNA was associated with all confirmed cervical intraepithelial neoplasia grade 3 and primary cervical cancers.