Population dynamics of serologically identified coinfections with human papillomavirus types 11, 16, 18 and 31 in fertile‐aged Finnish women

Abstract

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...

Differences in incidence and co‐occurrence of vaccine and nonvaccine human papillomavirus types in Finnish population before human papillomavirus mass vaccination suggest competitive advantage for HPV33

“…As previously described, 5 we calculated incidence rates (IRs) per 1,000 person-years. Incidence rate ratios (IRRs) with 95% confidence intervals (CIs) were used to estimate the risk of seroconversion for different HPV types after initial infection indicated by antibodies for only one HPV type (HPV 16ab only or HPV 18ab only ) or at least one HPV type (HPV 16ab or HPV 18ab ) compared to those individuals without antibodies to any of the seven HPV types.…”

“…5 A random subcohort of 3,600 women was stratified by calendar time at the midpoint of two consecutive pregnancies in three 3-year time bands and by age at the midpoint in four 3-year age bands (Table 1). In our previous studies, few HPV seroconversions were discovered after the age of 30 years.…”

“…To maximize study power, we selected twice as many random subjects in the older age groups between 23 and 28 years of age (Table 1). 5 3,21 A pool of serum samples from adolescent virginal females comprised the negative reference by which the absorbance cutoff levels were determined. Seroconversion between the first and the second pregnancy samples was defined by doubling of the absorbance level.…”

“…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][6][7][8][9][10] Furthermore, multiple infections are associated with an even higher increased risk of developing cervical neoplasia.…”

“…[3][4][5] Due to high transmission probability and tendency to persist concomitant infections by high-risk (hr) HPVs are common. [5][6][7][8][9][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.…”