Dynamics of oncogenic human papillomavirus infection

Background: Sexually transmitted oncogenic human papillomaviruses(HPVs), particularly HPV type 16, are the major cause of several human cancers, notably cervical and other anogenital cancers. The spread of these infections in human populations can be monitored using seroepidemiology. Several Nordic countries have established large, population based biological specimen banks. By registry linkages based on the personal identity numbers, it is possible to design prospective cohort studies where the dynamics of the infection and its association with later cancer development can be studied.

Study designs: To determine the stability of HPV antibody levels over time, the attack rates of HPV 16 and of cervical intraepithelial neoplasia grade III (CIN III) and identify possible strategies and sample sizes required for HPV vaccination efficacy trials, two age-stratified cohorts of pregnant women resident in Helsinki, Finland, were studied. The first cohort comprised 1656 women who became pregnant for the first time 1983-4 or in 1990-1 and again within a follow-up of 5 years and was tested for presence and persistence of HPV 16 antibodies. The second cohort comprised all primiparous women pregnant between 1983-94 and was followed-up to the end of 1994 to identify new cases of CINIII. To investigate the extent of HPV transmission during childhood, a consecutive series of 1,031 serum samples from children up to 13 years of age were analysed for presence of antibodies of the three major oncogenic HPV types (HPV16, 18, 33). To assess long-term trends over time of HPV infection, a cross-sectional serosurvey of the seroprevalence of HPV 16 was performed among 3,512 women resident in Stockholm, Sweden, participating in the population-based serological screening during pregnancy, in 1969, 1983 and 1989. To analyse the joint effect on cervical cancer risk of several different HPV types, 182 women with cervical cancer who had prediagnostic samples in population-based serum banks in Finland, Norway or Sweden as well as matched control women, were analysed for presence of antibodies to 5 common HPV types.

Results: Serum IgG antibody levels to HPV16 were found to be generally stable during several years of follow-up, suggesting that seropositivity can be used as a marker of cumulative HPV exposure in epidemiological studies. The seroprevalences of the major oncogenic HPV types among children were found to be low, suggesting that infection in childhood is not common. A highly significant increase in seroprevalence of the most common oncogenic HPV type (HPV16) had occurred among pregnant women in Stockholm, Sweden between 1969 and 1983. Between 1983 and 1989, the HPV 16 seroprevalences had been stable. Attack rates of HPV 16 were very high in young primiparous women in Finland and declined with increasing age of the women. There was a 12-fold antagonistic interaction between HPV 16 and HPV6/1 I in their joint risk for development of cervical cancer.

Conclusions: Several dynamic aspects of oncogenic HPV infection were revealed: i) Acquisition of infection is strongly age-related: uncommon in childhood, high attack rate among young mothers, low attack rate in mothers >25 years of age. ii) The spread of the infection in populations can change over time. iii) Different HPV types may antagonize the oncogenic effects of each other. Knowledge of these properties of the infection is important for design of primary prevention efforts, such as prophylactic vaccination trials.

List of scientific papers

I. af Geijersstam V, Kibur M, Wang Z, Koskela P, Pukkala E, Schiller J, Lehtinen M, Dillner J. (1998). Stability over time of serum antibody levels to human papillomavirus type 16. J Infect Dis. 177(6):1710-4.
https://pubmed.ncbi.nlm.nih.gov/9607854

II. af Geijersstam V, Eklund C, Wang Z, Sapp M, Schiller JT, Dillner J, Dillner L (1999). A survey of seroprevalence of human papillomavirus types 16, 18 and 33 among children. Int J Cancer. 80(4):489-93.
https://pubmed.ncbi.nlm.nih.gov/9935145

III. af Geijersstam V, Wang Z, Lewensohn-Fuchs I, Eklund C, Schiller JT, Forsgren M, Dillner J. (1998). Trends in seroprevalence of human papillomavirus type 16 among pregnant women in Stockholm, Sweden, during 1969-1989. Int J Cancer. 76(3):341-4.
https://pubmed.ncbi.nlm.nih.gov/9579570

IV. Luostarinen T, af Geijersstam V, Bjorge T, Eklund C, Hakama M, Hakulinen T, Jellum E, Koskela P, Paavonen J, Pukkala E, Schiller JT, Thoresen S, Youngman LD, Dillner J, Lehtinen M. (1999). No excess risk of cervical carcinoma among women seropositive for both HPV16 and HPV6/11. Int J Cancer. 80(6):818-22.
https://pubmed.ncbi.nlm.nih.gov/10074912

V. Kibur M, af Geijerstamm V, Pukkala E, Koskela P, Luostarinen T, Paavonen J, Schiller J, Wang Z, Dillner J, Lehtinen M. (2000). Attack rates of human papillomavirus type 16 and cervical neoplasia in primiparous women and field trial designs for HPV16 vaccination. Sex Transm Infect. 76(1):13-7.
https://pubmed.ncbi.nlm.nih.gov/10817062