Abstract
A total of 532 women with established cervical HPV infection have been prospectively followed (without treatment) since 1981 for a mean of 45 (SD 21) months. The patients were examined by colposcopy, PAP smears and/or punch biopsy every 6 months. The life-table method was applied to analyze the clinical course (i.e. regression and progression) of the HPV lesions, stratified by their colposcopic pattern, PAP smear findings and grade of CIN. During the follow-up, 107 (41.8%) of 256 patients with HPV-NCIN lesion in the first punch biopsy, experienced spontaneous regression. The corresponding proportions for HPV-CIN I, HPV-CIN II and HPV-CIN III lesions were 31.1%,34.2%, and 20.7%, respectively. In the overall comparison between these four groups, the heterogeneity in the probability of regression was statistically significant (p = 0.0005). Clinical progression was also associated significantly with the histological grade of the lesions in the first biopsy. Progression rate was only 5.8% for HPV-NCIN lesions, as compared to 12.3% for HPV-CIN I, 20% for HPV-CIN II, and 55.2% for HPV-CIN III. The probability of progression varied significantly between the four groups (p < 0.00001). Cumulative proportion of regression was 46% for patients with PAP smear class I, 84% with class II, and 82% for those with class III, cells, i.e. PAP smear was not of value in predicting the regression. However, PAP smears predicted clinical progression (p = 0.006 overall). Cumulative proportion of progression was low (18%) for lesions with normal colposcopic pattern on first clinical examination, as contrasted to 45% and 53% for those with mosaic and punctation, respectively (overall, p = 0.101). These data confirm the previous concepts on HPV-CIN as true precancer lesions with a definite potential for clinical progression. The value of histologic grade and, to lesser extent, the PAP smear findings as prognostic factors is emphasized.
Similar content being viewed by others
References
BMDP Statistical Software, 1985 Printing (1985): University of California Press, Berkeley, Los Angeles, London. pp. 557–575.
BoshartM.et al. (1984): A new type of papillomavirus DNA, its presence in genital cancer biopsies and in cell lines derived from cervical cancer. - EMBO J. 3: 1151–1157.
BrokerT.R.et al. (1986): Papillomaviruses: Retrospectives and prospectives. DNA Tumor Viruses. - Cancer Cells 4:17–36.
CampionM.et al. (1986): Progressive potential of mild cervical atypia: Prospective cytological, colposcopic, and virological study. - Lancet ii: 237–238.
CohenT. (1960): A coefficient of agreement for nominal scales. - Educ. Psychol. Meas. 20: 37–46.
deBruxJ.et al. (1983): Lesions condylomateuses du col uterin: evolution chez 2466 patients. - Bull. Cancer 70: 410–422.
DemeterT.et al. (1987): Detection of DNA of human papillomavirus types 6/11 and 16/18 in cell scrapings of the uterine cervix by filter in situ hybridization. Correlation with cytology, colposcopy and histology.- Eur. J. Epidemiol. 3: 404–413.
DurstM.et al. (1983): A papillomavirus DNA from a cervical carcinoma and its prevalence in cancer biopsy samples from different geographic regions. -Proc. Natl. Acad. Sci. USA 80: 3812–3814.
GissmannL.et al. (1984): Presence of Human papillomavirus in genital tumors. - J. Invest. Dermatol. 83: 26–28.
KadishA.S.et al. (1986): Human papillomavirus of different types in precancerous lesions of the uterine cervix: Histologic, immunocytochemical and ultrastructural studies. - Hum. Pathol. 17: 384–392.
KaplanE.C.et al. (1958): Nonparametric estimation from incomplete observations. - J. Am. Statist. Ass. 53: 457–481.
KnoxE.G.et al. (1988): Cancer of the cervix and the papilloma viruses. - Eur. J. Epidemiol. 4: 83–92.
KossL.G.et al. (1963): Some histological aspects of behavior of epidermoid carcinoma in situ and related lesions of the uterine cervix. A long-term prospective study. - Cancer 9: 1160–1211.
KossL.G. (1987): Cytologic and histologic manifestations of human papillomavirus infection of the female genital tract and their clinical significance.- Cancer 60: 1942–1950.
15.KulskiJ.K.et al. (1987): DNA sequences of human papillomavirus types 11, 16 and 18 in invasive cervical arcinoma of Western Australian women. -Immunol. Cell Biol. 65: 77–84.
LeeE.T. (1984): Statistical methods for survival data analysis. Life Time Learning Publications, Belmont, California, pp. 9–156.
MacnabJ.C.M.et al. (1986): Human papillomavirus in clinically and histologically normal tissue of patients with genital cancer. - N. Engl. J. Med. 315: 1052–1058.
MantelN. (1966): Evaluation of survival data and two new Rank order statistics arising in its consideration.- Cancer Chemother. Rep. 50: 163–170.
MeiselsA.et al. (1976): Condylomatous lesions of cervix and vagina. I. Cytologic patterns. - Acta Cytol. 20: 505–509.
MitchellH.et al. (1986): Prospective evaluation of risk of cervical cancer after cytological evidence of Human papillomavirus infection. - Lancet i: 573–575.
MunozN.et al. (1988): Does human papillomaviruses cause cervical cancer? The state of the epidemiological evidence. - Br. J. Cancer 57: 1–5.
MurdochJ.B.et al. (1988): Histological and cytological evidence of viral infection and human papillomavirus type 16 DNA sequences in cervical intraepithelial neoplasia and normal tissue in the west of Scotland: evaluation of treatment policy. - Br. Med. J. 296: 381–385.
NashJ.D.et al. (1987): Biologic course of cervical human papillomavirus infection. - Obstet. Gynecol. 69: 160–169.
NasiellK.et al. (1986): Behavior of mild cervical dysplasia during long-term follow-up. - Obstet. Gynecol. 67: 665–669.
OrielJ.D. (1981): Genital warts. - Sex. Transm. Dis. 8: 326–329.
PetoR.et al. (1977): Design and analysis of randomized clinical trials requiring prolonged observation of each patient. II. Analysis and examples. - Br. J. Cancer 35: 1–39.
SPSS-X Users Guide (1983): McGraw-Hill Book Company, New York, 1983, pp. 96–104.
SyrjänenKJ (1983): Human papillomavirus (HPV) lesions in association with cervical dysplasias and neoplasias. - Obstet. Gynecol. 62: 617–624.
SyrjänenK.et al. (1984): Sexual behaviour of the females with Human papillomavirus (HPV) lesions in the uterine cervix. - Brit. J. Vener. Dis. 60: 243–248.
SyrjänenK.et al. (1985): Human papillomavirus (HPV) type as an important determinant of the natural history of HPV infections in uterine cervix. -Eur. J. Epidemiol. 1: 180–187.
SyrjänenK.et al. (1985): Cervical papillomavirus infection progressing to invasive cancer in less than three years. - Lancet i: 510–511.
SyrjänenK.et al. (1985): Natural history of HPV infections in uterine cervix as determined by prospective follow-up. In: P.M. Howley and T.R. Broker (eds). Papilloma Viruses: Molecular and Clinical Aspects, UCLA Symposia on Molecular and Cellular Biology, Alan R. Liss, Inc., New York. - New Series, 32: 31–45.
SyrjänenK.J. (1987): Biology of Human papillomavirus (HPV) infections and their role in squamous cell carcinogenesis. - Med. Biol. 65: 21–39.
Syrj:anenK.et al. (1987): Assessing the biological potential of human papillomavirus infections in cervical carcinogenesis. - Cancer Cells 5: 281–289.
SyrjänenK.J.et al. (1987): Cervical PAP smears in assessment of the natural history of cervical Human papillomavirus (HPV) infections in prospectively followed-up women. - Acta Cytol. 31: 855–865.
SyrjänenK.et al. (1988): Factors associated with clinical progression of cervical human papillomavirus (HPV) infections during a long-term prospective follow-up. - Brit. J. Obstet. Gynaecol. 95: 1096–1102.
Syrjänen K. et al. (1988): Factors associated with the clinical behavior of cervical human papillomavirus (HPV) infections during a long-term prospective follow-up. - Cervix & l.f.g.t. In press.
VdyrynenM. (1986): Natural history of cervical HPV infections. Colposcopic assessment and biological considerations. Publications of the University of Kuopio, Orig. Rep. 2: pp. 1–83.
WellsM.et al. (1987): Demonstration of human papillomavirus types in paraffin processed tissue from human anogenital lesions by in-situ DNA hybridization. - J. Pathol. 152: 77–86.
Author information
Authors and Affiliations
Additional information
Corresponding author.
Laboratory of Pathology & Cancer Research, Finnish Cancer Society, Kuopio
Rights and permissions
About this article
Cite this article
Kataja, V., Syrjänen, K., Mäntyjärvi, R. et al. Prospective follow-up of cervical HPV infections: Life table analysis of histopathological, cytological and colposcopic data. Eur J Epidemiol 5, 1–7 (1989). https://doi.org/10.1007/BF00145037
Issue Date:
DOI: https://doi.org/10.1007/BF00145037