SPONTANEOUS EVOLUTION OF INTRAEPITHELIAL LESIONS ACCORDING TO THE GRADE AND TYPE OF THE IMPLICATED HUMAN PAPILLOMAVIRUS (HPV)

Because of the fact that any meaningful classification should bear a c lose relationship to the biological behavior of the lesions, the usefu lness of all new classifications of cervical precancer lesions can onl y be established by well controlled prospective follow-up studies. How ever, several methodological and conceptual problems are encountered i n the natural history studies conducted during the past several decade s. While reviewing the available prospective follow-up studies on cerv ical intraepithelial neoplasia (GIN), Ostor (1993) found 3529 cases of CIN 1, of which 57% showed regression, persistence was found in 32%, progression to CIN III in 11%, and progression to invasive cancer in 1 % of cases. The corresponding figures for CIN II were 43%, 35%, 22%, a nd 5%, respectively. The recognition of the association between human papillomavirus (HPV) and CIN has further complicated the assessment of the natural history of cervical precancer lesions. Results from the e arly prospective follow-up studies are remarkably consistent, however. Progression from HPV-NCIN (i.e., koilocytosis without GIN) to CIN I o r greater was reported for 18 (8%) of 232 women followed by Syrjanen e t al. for an average of 25 months, for 26 (8%) of 314 women followed b y de Brux et al. (1981) for 15 to 18 months, and for 113 (13%) of 846 women followed for up to six years by Mitchell et al. During a 42-mont h follow-up period, 100% progression rate was found in 1269 women with HPV-CIN I, and in 17% of 762 women with HPV-CIN II by de Brux et al. (1983). The spontaneous regression rates were 53% and 39% in these coh orts, respectively. This is fully consonant with our experience from a n almost 14-year follow-up of 530 women in Kuopio, where the spontaneo us regression rate seems to increase in parallel with the extent of th e followup time, currently being 66.7% for HPV-NCIN and 55.7% for HPV- CIN I. The figures for progression are 6.3% and 14.2%, respectively. I t is obvious that the probability of a cervical precancer lesion to pr ogress into an invasive disease increases with the severity of the aty pia. Another distinct prognostic factor is HPV type, HPV 16 lesions po ssessing a significantly higher risk for progression than infections b y other HPV types. The follow-up data also indicate, however, that eve n the high grade lesions may spontaneously regress, which should have important implications in therapy. The continuous problem still remain s; these natural history observations only apply to a large series of women but are of little help in predicting the disease outcome in indi vidual women.