Genital human papillomavirus (HPV) infections and their importance for the handling of precancerous lesions of the cervix uteri

Abstract: Background: The development of cervical carcinoma, in a vast majority of cases, is closely related to infections with certain types of the human papillomavirus (HPV). The virus is supposed to exert its oncogenic effect mainly through interference with two proteins that are responsible for growth arrest as a response to DNA damage. The infection is an early event in the development of this tumour, and the further carcinogenesis probably necessitates additional co-factors. The development of invasive carcinoma of the cervix uteri can to some extent be prevented through cytological health control screening and subsequent treatment of detected precursor lesions. Many cases of such cancer will, however, develop in spite of screening, mainly due to lack of sensitivity of the cytological test. One way to improve the sensitivity in detecting patients at risk for developing cervical carcinoma may be an additional search for HPV infections. This can be done using morphology, molecular biology or immunology; all these techniques vary in sensitivity and specificity. Aims: These studies were under-taken to evaluate the diagnostic significance of various cytomorphological findings; to validate and compare different diagnostic methods for the diagnosis of an HPV infection and to exploit the possible clinical use of HPV testing as a mean to detect precancerous lesions in otherwise healthy women and as follow-up after treatment for such lesions. Findings: All tested cytomorphological criteria were significantly more common among infected patients, although only three of them: koilocytosis, parakeratosis and/or dyskeratosis and karyorrhexis, were of major diagnostic importance. These morphological criteria, Southern blot and PCR analysis canall be used to specifically diagnose HPV infections. The clinical sensitivity of the cytological algorithm is <40%, of Southern blot analysis - outstanding for typing purposes - 60% or lower, while PCR analysis of archival smears is highly sensitive and specific. HPV DNA can be detected many years before the development of cervical cancer, even in cytologically normal smears, but the specificity in detecting risk patients is insufficient for screening purposes. HPV DNA analysis seems to be the best way to detect patients at risk for recurring disease following conization for CIN 3. These results also in-dicate that the successful management of these precancerous lesions depended on both radicality of surgery and on the clearance of persistent HPV infection.