Vaccines against high-risk (hr) human papillomaviruses (HPVs) causing cervical cancer may soon be licensed. Thus, nature of HPV epidemics needs to be studied now. Random sampling for studies on HPV epidemiology was done from all 230,998 women belonging to the population-based Finnish Maternity Cohort and having a minimum of 2 pregnancies between 1983 and 1994. First pregnancy serum specimens were retrieved for 7,805 subjects, and were analyzed for antibodies to HPV6/11, 16 and 18 with standard ELISAs. HPV16 seroprevalence almost doubled from the 1980s to the 1990s, and the epidemic spread to new areas in 23-31 year olds, i.e. the bulk of pregnant female population in the southwest part of the country. The HPV16 epidemic in the 14-22 year olds in 1983-1988 (1961-1974 birth cohorts) and in the 23-31 year olds in 1989-1994 (1958-1971 birth cohorts) overlapped with strong clustering of HPV16 and HPV18 infections in the latter (odds ratio 8.0, 95% confidence interval 6.6-9.7). Similar clustering of HPV16 and HPV6/11 infections was not found. The epidemic and the clustering may be due to high transmission probability of the hrHPV types and increase in sexual activity of the index birth cohorts. ' 2006 Wiley-Liss, Inc.Key words: cervical cancer; vaccination; population-based followup; cohort study; cervical neoplasia; cancer registry; human papillomavirus Genital infections with human papillomaviruses (HPVs) peak shortly after the beginning of sexually active life between 18 and 22 years of age.1,2 There are about 40 HPV types causing genital infections. The types in Finland are identical to those seen in the other western/European countries: HPV6/11,16,18,31, 33 and 45. 3 Co-infection of HPV types is not uncommon, 4,5 but factors affecting their acquisition differ between the high risk (hr) and the low risk (lr) HPV types.6-9 Moreover, there is antagonism between hrHPVs and lrHPVs in cervical carcinogenesis. 10,11 During the past 30 years, sexual behavior has considerably changed in Finland with increases both in sexual activity and risktaking behavior among females.12 This has resulted in increasing trends of hrHPVs (e.g., HPV16) but not lrHPVs (e.g., HPV6/11) incidence in pregnant Finnish women since 1980s.13 Also, during the last 10 years, the incidence of cervical cancer (CxCa) among fertile-aged women has rapidly increased in Finland.14,15 Moreover distribution of hrHPV types has changed in the CxCa cases, and a new hrHPV type (HPV45) emerged during the 1990s (data on file). 16,17 This suggests that hrHPV epidemics in Finland have been in a dynamic state for the past 30 years.Vaccines against the major hrHPV types (HPV16 and HPV18) may be licensed during year 2006, and use of the HPV16/18 vaccine may considerably change the epidemic situation in the young, turning smaller or larger groups of susceptible (vaccine implementation at private or societal level) to group of immunes. Size of the immune group, in the vaccination era, will be determined both by vaccine coverage and changes in sexual behavior, and de...

To understand likelihood of type replacement after vaccination against the high-risk human papillomavirus (HPV) types, we evaluated competition of the seven most common genital HPV types in a population sample of unvaccinated, fertile-aged Finnish women. First trimester sera from two consecutive pregnancies were retrieved from 3,183 Finnish women (mean age, 23.1 years) of whom 42.3% had antibodies to at least one HPV type (6/11/16/18/31/33/45) at the baseline. Antibody positivity to more than one HPV types by the second pregnancy was common among the baseline HPV seropositives. However, compared to baseline HPV-seronegative women, significantly increased incidence rate ratios (IRRs), indicating an increased risk to seroconvert for another HPV type, were consistently noted only for HPV33 among baseline HPV16 or HPV18 antibody (ab)-positive women: HPV 16ab only fi 16&33ab IRR 2.9 [95% confidence interval (CI) 1.6-5.4] and HPV 18ab only fi 18&33ab IRR 2.5 (95% CI 1.1-6.0), irrespectively of the presence of antibodies to other HPV types at baseline: HPV 16ab fi 16&33ab IRR 3.2 (95% CI 2.0-5.2) and HPV 18ab fi 18&33ab IRR 3.6 (95% CI 2.1-5.9). Our findings suggest a possible competitive advantage for HPV33 over other genital HPV types in the unvaccinated population. HPV33 should be monitored for type replacement after HPV mass vaccination.There are at least 40 genital human papillomavirus (HPV) types classified into oncogenic and nononcogenic types. 1 Transmission probability of the most common type, HPV16, has been estimated to be up to 60%. 2 The presence of multiple types in the sexually active population is common, and the epidemic state of some (e.g., HPV16) but not all HPV types is dynamic (increasing) at the population level in Finland. [3][4][5] Due to high transmission probability and tendency to persist concomitant infections by high-risk (hr) HPVs are common. 5-10 Furthermore, multiple infections are associated with an even higher increased risk of developing cervical neoplasia. 10 Two highly efficacious HPV vaccines have now been licensed world wide. [11][12][13][14] By diminishing the pool of HPVsusceptible individuals and preventing transmission, HPV vaccination could rapidly change the ecosystem of genital HPV types. Consistent crossprotection provided by the current HPV6/11/16/18 and HPV16/18 vaccines against a number of closely HPV16-or HPV18-related HPV31 and HPV45, respectively, 15-17 makes the situation even more challenging. Replacement of vaccine hrHPV types in an ecological niche induced by mass vaccination may be possible. 18 The vaccine manufacturers already have more polyvalent HPV vaccines under development to tackle possible situations.We have previously reported the dynamic nature of epidemic caused by HPV16 in Finland 3 and about increased risk of acquiring HPV16 and HPV18 coinfections over time. 4,5 Replacement of vaccine-covered pneumococcal types with nonvaccine types predicted 15 years ago, has been verified after implementation of pneumococcal vaccination and threatens to jeopardize...

Licensed human papillomavirus (HPV) vaccines are expected to prevent high-risk (hr) HPV-infections (most notably types 16 and 18). Whether HPV vaccination will change the distribution of hrHPVs at the population level is open, since competition between HPV types is not well understood. Two stratified random subcohorts (1983-1997 and 1995-2003) of 7,815 and 3,252 women with a minimum of 2 pregnancies (<32 years) were selected from the Finnish Maternity Cohort. Using ELISA based on virus-like particles (VLP), we determined antibodies to HPV11, 16, 18 and 31 in paired sera of the women and used Poisson regression models to estimate the risk of further infection with other HPV types in those positive for HPV16 or HPV18 at baseline. Baseline HPV16 seropositivity was associated with increased risk of later infections with HPV18 (3.1, 95% CI: 1.7, 5.6). HPV18 seropositivity was associated with increased risk of HPV16 (3.9, 95% CI: 2.5, 6.1). Our observations favor a coinfection rather than superinfection model for the different HPV types and are not suggestive for typereplacement following HPV vaccination. Coinfections of different HPV types in the same individual, both concurrent and sequential, are known to occur. 4,5 Past infections with a low-risk (lr) HPV types decrease the risk of ICC associated with hrHPV types close to unit relative risk, 6,7 whereas cross-sectional studies have found increased relative risk of ICC also in cases with multiple hrHPVs. 2,8,9 In Finland, population-based organized screening and treatment for cervical cancer started in the 1960s and reduced the incidence of ICC from 15 to 3 per 100,000 in 20 years. 10 However, since 1990, the incidence of ICC among fertile-aged women has been increasing again. 11,12 This is probably to a great extent due to increasing sexual risk-taking behavior and steadily increased incidence of HPV16 among Finnish women. 13,14 However, the role of other hrHPV types, which have also increased in prevalence in Finland since the 1990s, is unknown. 15,16 Two prophylactic vaccines, one against HPV types 16 and 18, and another against HPV types 6, 11, 16 and 18 have been licensed. [17][18][19] What will happen to the distribution of HPV types at the population level following vaccination is an enigma of HPV epidemiology? 20 Broad vaccine induced cross immunity against nonvaccine HPV types would be the best case scenario. Preliminary data suggest that vaccination targeting HPV16 and HPV18 induces cross protection also against HPV31 and HPV45 infection at least up to 4.5 years with 94% (95% confidence interval: 63%, 100%) and 55% (12%, 78%) vaccine efficacy. 18 On the other hand, vaccination could result over time in HPV type-replacement by other, immunologically distinct hrHPV types, not targeted by the vaccine. [21][22][23] The impact of (cross immunity from) natural infections on HPV type distribution and its dynamics at the population level is very difficult to evaluate, and there are only a few studies about the competition of different HPV types. 5,[24][25][26][2...

Pregnancy reduces maternal risk of breast cancer in the long-term, but the biological determinants of the protection are unknown. Animal experiments suggest that estrogens and progesterone could be involved, but direct human evidence is scant. A case-control study (536 cases, 1,049 controls) was nested within the Finnish Maternity Cohort. Eligible were primiparous women, who delivered at term a singleton offspring before age 40. For each case, two individually matched controls by age (±6 months) and date of sampling (±3 months) were selected. Estradiol, estrone, and progesterone in first-trimester serum were measured by High Performance Liquid Chromatography Tandem Mass Spectrometry and sex-hormone binding globulin (SHBG) by immunoassay. Odds ratios (OR) and 95% confidence intervals (CI) were estimated through conditional logistic regression. In the whole study population, there was no association of breast cancer with any of the studied hormones. In analyses stratified by age at diagnosis, however, estradiol concentrations were positively associated with risk of breast cancer before age 40 (upper quartile OR, 1.81; CI, 1.08-3.06), but inversely associated with risk in women who were diagnosed ≥age 40 (upper quartile OR, 0.64; CI, 0.40-1.04), pinteraction 0.004. Risk estimates for estrone mirrored those for estradiol, but were less pronounced. Progesterone was not associated with risk of subsequent breast cancer. Our results provide initial evidence that concentrations of estrogens during the early parts of a primiparous pregnancy are associated with maternal risk of breast cancer and suggest that the effect may differ for tumors diagnosed before and after age 40.

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