A causal association of high risk HPV persistent infections with cervical cancer is firmly established by epidemiological and experimental evidence. Since HPV is considered a necessary factor for cervix carcinoma development and disease severity, the HPV DNA persistence may represent an indicator of both therapy effectiveness and risk of recurrence. The presence of HPV in locally advanced cervical carcinoma was analysed at the beginning of therapy, shortly after treatment and during follow-up, in 18 patients with cervix carcinoma treated by radio/chemotherapy. Persistence of HPV DNA sequences was revealed in 62.5% (10/16) of HPV positive patients, in which the HPV type and its physical status were exactly the same as at the onset of therapy, even many years after surgery. Interestingly, in two patients the HPV18 sequence analysis detected the same point mutations in the samples before and after the chemotherapy, and during the follow-up. HPV DNA clearance was associated with a better patient outcome because the majority of the HPV cleared women showed a complete response (6/6), no disease recurrence (4/6), and are still alive. Nevertheless, statistically significant association was seen only with complete responses versus partial or no responses. In conclusion, we demonstrated that HPV DNA positive tumour cells might persist for years in the genital epithelia, even after the surgical removal of the cervix and that HPV DNA detection after therapy is a valid and significant (p=0.03) tool to assess the efficacy of the treatment.