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Human papillomavirus antibody reactivities to vulvar precancerous lesions were reported but the role of human papillomavirus in some of the lesions is still unclear. Reports supported the role of high-risk human papillomavirus types, mainly human papillomavirus-16, in the pathogenesis of different vulvar lesions with atypia.

Women with cervical cancer who have antibodies in their blood against human papillomavirus 16 appear to have a better prognosis than women who do not, according to a study of 68 women with cervical cancer and 65 healthy women. The presence of antibodies against the virus may indicate that the virus has not yet inserted its DNA into the host cell.

Background: A growing body of evidence supports the hypotheses that the retinoic acid receptor [Beta]2 (RAR-[Beta]2) gene is a tumor suppressor gene and that the chemopreventive effects of retinoids are due to induction of RAR-[Beta]2. RAR-[Beta]2 expression is reduced in many malignant tumors, and we examined whether methylation of RAR-[Beta]2 could be responsible for this silencing. Methods: RAR-[Beta]2 expression was studied by reverse transcription--polymerase chain reaction (RT-PCR) analysis in eight breast cancer cell lines that were either treated with the demethylating agent 5-aza-2'-deoxycytidine and subsequently with all-trans-retinoic acid (ATRA) or left untreated. Sodium bisulfite genomic sequencing was used to determine the locations of 5-methylcytosines in the RAR-[Beta]2 genes of three of these cell lines. In 16 breast cancer biopsy specimens and non-neoplastic breast tissue, methylation-specific PCR was used to determine the methylation status of RAR-[Beta]2, and, in 13 of the specimens, RT-PCR analysis was used to detect RAR-[Beta]2 expression. Results: Cell lines SK-BR-3, T-47D, ZR-75-1, and MCF7 exhibited expression of RAR-[Beta]2 only after demethylation and treatment with ATRA. The first exon expressed in the RAR-[Beta]2 transcript was methylated in cell lines ZR-75-1 and SK-BR-3. Six breast cancer specimens showed methylation in the same region of the gene. No expression of RAR-[Beta]2 was found in any grade III lesion. An inverse association between methylation and gene expression was found in all grade II lesions. The RAR-[Beta]2 gene from non-neoplastic breast tissue was unmethylated and expressed. Conclusions: Methylation of the RAR-[Beta]2 gene may be an initial step in breast carcinogenesis; treatment of cancer patients with demethylating agents followed by retinoic acid may offer a new therapeutic modality. [J Natl Cancer Inst 2000;92:826-32]