HPV DNA POSITIVITY AND NATURAL-KILLER-CELL ACTIVITY IN THE CLINICAL OUTCOME OF MILD CERVICAL DYSPLASIA - INTEGRATION BETWEEN VIRUS AND IMMUNE-SYSTEM

The objective was to examine the prevalence of human papillomavirus (H PV) DNA infection in mild cervical dysplasia and to evaluate longitudi nally the persistence of HPV DNA positivity in an observational study. aiming at identifying the role of peripheral blood lymphocyte natural killer activity in the natural history of dysplastic disease. Twenty- three patients with histologically proven mild cervical dysplasia were selected. The HPV DNA positivity, determined by polymerase chain reac tion, and cervical dysplasia were monitored cytologically and colposco pically at the 3rd (time 1), 6th (time 2) and 12th months (time 3), an d defined by biopsies for routine histology taken at times 2 and 3. Fo r each patient included in the study, the immune reactivity was evalua ted at the time of diagnosis and afterwards, longitudinally during the follow-up. The immune status analysis included T lymphocyte subsets ( CD3, CD4, CD8, CD56, CD16 monoclonal antibodies by Beckton Dickinson, Mountain View, Calif., USA) and determinations of natural killer cell activity (against the sensitive cell line K 562). Eighteen out of the 23 women with mild cervical dysplasia (78.3%) were found positive for HPV DNA, with a significantly high representation of HPV DNA type 16 ( 55.6% of cases). At the end of the study, 12 out of 18 HPV-DNA-positiv e women became negative (defined by two or more negative tests) for th e original HPV DNA type, with 66.7% of spontaneous HPV DNA negativizat ion rate (p = 0.6). In 83.3% of the women with definitive HPV DNA nega tivization and in 7.5% of those with a constant HPV DNA negativity, th e resolution of HPV DNA infection was associated with a clinical-patho logic remission of the lesion. Patients with spontaneous HPV DNA negat ivization and/or clinical-pathologic resolution of cervical dysplasia had a significantly higher mean value of natural killer activity than those with persistent disease. No significant modifications were obser ved with respect to lymphocyte subsets. The longitudinal evaluation of natural killer activity showed constantly low values of natural cytot oxicity in patients with persistent dysplasia, while women with regres sive lesions had a significant increase in immune reactivity during th e follow-up. The majority of patients with mild HPV-DNA-associated dys plasia can be followed with confidence and with the expectation that t he minimal degree of dysplasia will eventually disappear. The evaluati on of natural cytotoxicity is a useful parameter of functional immune status, correlated with the natural history of the disease.