Forty-two patients with recurrent respiratory papillomatosis (RRP) were accepted into a multicenter prospective study in 1983 to 1990, treated with alfa-IFN 3 MU/m 2 3 times a week and then followed-up until August 1, 2003. All the patients who had disease progression with pulmonary spread were characterized by insufficient response to IFN-therapy and detection of HPV type 11. Five patients (4/5 smokers) presented malignant transformation in lungs or nasopharynx (mean RRP duration was 27.2 +/- 8 years from RRP onset and 14.6 +/- 6.3 years from pulmonary spread until malignant transformation) with persistent RRP in larynx. The results of long-term follow-up in RRP patients with HPV 11 underline the necessity of reanalyzing the current therapy.

The obtained results revealed maximal effectiveness of IFN-alpha therapy in RRP patients with HPV 6 as compared with HPV 11. The association of HPV 11 with a worse long-term response to IFN-alpha therapy and a higher incidence of malignant transformation and mortality is clinically important and indicates the necessity of HPV typing in RRP patients after the first biopsy.

Patients with HPV type 11, a severity score >4, a high number of surgical procedures prior to interferon-alpha therapy and a high basal 2',5'-oligoadenylate synthetase activity should be considered at high risk of an aggressive clinical course, often with spread to lower airway passages, malignant transformation and death. Human papilloma virus type, score for recurrent respiratory papillomatosis severity, number of surgical procedures and 2',5'-oligoadenylate synthetase activity showed significant association with response to interferon-alpha therapy and the long-term clinical course, so these factors have value in predicting prognosis in recurrent respiratory papillomatosis.