Human papillomavirus genome integration in multifocal vulvar Bowen's disease and squamous cell carcinoma

Human papillomavirus (HPV) is an important aetiological agent in cervical carcinomas and in malignant skin tumours. Integration of the HPV DNA into host genome is one of the most important risk factors for malignant transformation. We report a patient with multiple black plaques and an erythematous nodule on her vulva. On histological examination, multifocal vulvar Bowen's disease (BD) and invasive squamous cell carcinoma (SCC) were found. An amplification of papillomavirus oncogene transcripts (APOT) assay showed that two locations of BD had only episome-derived HPV16 transcripts, but the other two sites of BD and the nodule of invasive SCC had HPV16 transcripts derived from integration. Sequencing analysis revealed that the invasive SCC had its integration site at 8q24, the Myc locus. Our results suggest that the APOT assay in multiple sites of the same patient may be a valuable tool for evaluation of the clinical degree of malignancy for vulvar BD.