HPV16 and HPV18 integration into host cell DNA contributes to malignant transformation. Viral physical status was compared among samples from different tumour areas, and from tumour and paired non-lesional adjacent epithelium, in order to evaluate the levels of HPV integration that could account for local recurrences. Fifty-nine surgical biopsies were collected from 24 women with HPV16 and/or HPV18-associated genital tumours, including 3 preinvasive and 21 invasive lesions. HPV integration was analysed by type-specific and multiplex PCRs for E6, E1 and E2 sequences. Nine tumours contained HPV16, 1 HPV18 and 14 both viruses. Intra-tumour heterogeneity occurred in 3 of the 10 tumours with multiple sampling (30%), including different HPV16 physical forms between core and periphery in 2 cases, and different type of HPV infection in 1 case. Almost all tumours contained integrated forms of either HPV16 and/or HPV18. Analysis of the 15 tumour-free tissues displayed 11 HPV-positive (73%) and 4 HPV-negative tissues. HPV16 was pure integrated in 1 case, mixed in 1 and episomal in 8, whereas HPV18 was integrated in all 6 positive tissues (100%). When compared to the corresponding tumour, the positive control mucosa contained the same HPV type and the same physical status as the tumour in 6 cases, whereas 5 samples contained different HPV16 physical forms, episomal DNA being more frequent than in the lesion. These data showing the presence of high-risk HPV integrated forms in normal mucosa, especially in HPV18-positive cases, indicate that the research of viral integration in the adjacent tumour tissues may be a valuable tool in assessing risk factors for local recurrences.

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