Human papillomavirus (HPV) is the most common sexually transmitted infectious agent; its 14 oncogenic types are causally associated with 5-10% of all cancers. The major structural HPV protein ...self-assembles into immunogenic virus-like particles. Two licensed HPV vaccines--the bivalent vaccine comprising HPV types 16 and 18, and the quadrivalent vaccine comprising HPV types 6, 11, 16 and 18--have proven to be safe and efficacious against 6-month-persistent cervical infections of HPV16 and HPV18 and associated precancerous lesions, and both have efficacies of 90-100%. Among baseline HPV-negative adolescent females, vaccine efficacies against the immediate precursor of cervical cancer (intraepithelial neoplasia grade 3) irrespective of HPV type are 93.2% and 43.0% for the bivalent and quadrivalent vaccines, respectively. The quadrivalent vaccine is efficacious (>75% vaccine efficacy) against any of the more-severe precursors of vulval, vaginal and anal cancers. A strong increase in vaccine efficacy with increasing severity of the precancerous lesion is explained by accumulation of the most-oncogenic HPV types 16 and 18 in these lesions. Therefore, prophylactic HPV vaccination will exceed the best results from screening for cancer. With the extremely efficacious prophylactic HPV vaccines, the focus of organized intervention (vaccination and screening) programmes should, however, shift from reducing the HPV disease burden to controlling the prevalence of oncogenic HPV (and nononcogenic HPV) types. Eradication of the major oncogenic HPV types should be pursued.
Abstract
Background
Although human papillomavirus (HPV) vaccines are highly efficacious in protecting against HPV infections and related diseases, vaccination may trigger replacement by nontargeted ...genotypes if these compete with the vaccine-targeted types. HPV genotype replacement has been deemed unlikely, based on the lack of systematic increases in the prevalence of nonvaccine-type (NVT) infection in the first decade after vaccination, and on the presence of cross-protection for some NVTs.
Methods
To investigate whether type replacement can be inferred from early postvaccination surveillance, we constructed a transmission model in which a vaccine type and an NVT compete through infection-induced cross-immunity. We simulated scenarios of different levels of cross-immunity and vaccine-induced cross-protection to the NVT. We validated whether commonly used measures correctly indicate type replacement in the long run.
Results
Type replacement is a trade-off between cross-immunity and cross-protection; cross-immunity leads to type replacement unless cross-protection is strong enough. With weak cross-protection, NVT prevalence may initially decrease before rebounding into type replacement, exhibiting a honeymoon period. Importantly, vaccine effectiveness for NVTs is inadequate for indicating type replacement.
Conclusions
Although postvaccination surveillance thus far is reassuring, it is still too early to preclude type replacement. Monitoring of NVTs remains pivotal in gauging population-level impacts of HPV vaccination.
It is probably still too early to preclude human papillomavirus genotype replacement after a decade of postvaccine surveillance, because replacement could occur after a honeymoon period owing to the combination of infection-induced cross-immunity and vaccine-induced cross-protection for a nonvaccine type.
Human papillomavirus (HPV) vaccination is predicted to lower the positive predictive value (PPV) of cytology.
We included 153,250 girls born between 1989 and 1993, resident in Sweden since the ...introduction of HPV vaccines (October 2006) and attending cervical screening at age 23 years. We assessed their first cytology and following histopathological diagnosis using Swedish National Cervical Screening Registry (NKCx). By linkage with the national Swedish HPV vaccination registry, we determined PPV of abnormal cytology for cervical intraepithelial neoplasia grade 2 or worse (CIN2+) and the differences with 95% confidence intervals (CIs) according to vaccination status.
The PPV of high-grade cytology for CIN2+ was 69.9% (95% CI, 67.9-71.9), 64.9% (95% CI, 59.8-69.8) and 57.4% (95% CI, 50.9-63.7) among women unvaccinated, initiating vaccination at age 17-22 years and initiating vaccination before age 17 years, corresponding to reduction in PPV by 8% (95% CI, 0-15%) and 17% (95% CI, 7-26%) in vaccinated groups after adjustment for birth cohort, respectively.
The PPV of cytology for CIN2+ decreased among vaccinated women, and the decrease was stronger for girls vaccinated at younger ages. A switch from cytology to HPV testing might potentially improve the screening performance.
Age-specific type-distribution of high-risk human papillomavirus (hrHPV) in cervical precancerous lesions is subject to change in the HPV vaccination era. Knowing the pre-vaccination ...type-distribution helps to anticipate changes induced by mass vaccination and optimize screening.
We recruited 1279 women referred to colposcopy for abnormal cytology into a population-based study on HPV type distribution in diagnostic cervical samples (ISRCTN10933736). The HPV genotyping findings were grouped as: HPV16/18+, other hrHPV+ (HPV31/33/35/39/45/51/52/56/58/59/66/68), non-vaccine targeted hrHPV+ (HPV35/39/51/56/59/66/68), low-risk HPV, and HPV negative. We estimated the HPV group-specific prevalence rates according to diagnostic histopathological findings in the age groups of <30 (n = 339), 30–44.9 (n = 614), and ≥45 (n = 326).
Altogether 503 cases with high grade squamous intraepithelial lesion or worse (HSIL+) were diagnosed. More than half, 285 (56.7%) of HSIL+ cases were associated with HPV16/18: 64.3% (101/157) in women <30 years (reference group), 58.4% (157/269) in women 30–44.9 years (risk ratio (RR) 0.91, 95% confidence interval (95% CI) 0.78–1.06), and 35.1% (27/77) in women ≥45 years of age (RR 0.55, 95% CI 0.39–0.75). Conversely, other hrHPV's were associated with 191 (38.0%) of HSIL+: 31.9% (50/157) in women <30, 36.8% (99/269) in women 30–44.9 years, 54.6% (42/77) and in women ≥45 (RR 1.71, 95% CI 1.26–2.33). The proportion of non-vaccine targeted hrHPV and HPV negative HSIL+ increased with advancing age.
Pre-vaccination HPV type distribution in HSIL+ was distinctly polarised by age with HPV16/18 attributed disease being markedly more prevalent in women aged <30. In the older women the other hrHPV types, however, dominated suggesting a need for more age-dependent screening strategies.
•HPV distribution was markedly polarised by age in women referred to colposcopy.•HPV16/18 was twice as common in women <30 years than in women ≥45 with HSIL lesions.•In women ≥45 years other high-risk HPVs were more common in HSIL lesions.•In women ≥45 years approximately 10% of HSIL lesions were negative for high-risk HPV.
The aim of the study was to examine the construct validity of the Three-Factor Eating Questionnaire -R18 (TFEQ-R18), a measure of eating behaviour, and to evaluate cognitive restraint, uncontrolled ...eating and emotional eating in a sample of adolescent and young adult females of different weights.
Subjects were 2 997 females, aged 17 to 20 years, who participated in a phase III human papillomavirus vaccination trial in Finland in 2004 - 2009.Self-administered questionnaires and weight and height measurements were used. The factor structure of the TFEQ-R18 was verified by factor analysis. Connections between measured eating behaviour and Body Mass Index (BMI) were tested using analysis of variance.
The original factor structure of the TFEQ-R18 was replicated: six of the eighteen items measured cognitive restraint, nine measured uncontrolled eating, and three measured emotional eating. On average, higher BMI was associated with higher levels of cognitive restraint (p < 0.001) and emotional eating (p < 0.001), but not with uncontrolled eating.
Structural validity of the TFEQ-R18 was good in this sample of young Finnish females with a varying range of body weights. Use of the instrument as a measure of eating behaviour was thus corroborated. Connections of restrained and emotional eating with BMI were in accordance with previous findings from young females.
Evidence suggests that the hormonal milieu of pregnancy is an important determinant of subsequent cancer and other chronic diseases in both the mother and the offspring. Many of the existing ...maternity and birth cohorts include specimens drawn only once during pregnancy. How well a single blood specimen collected during a pregnancy characterizes exposure to these hormones throughout gestation, and also in subsequent pregnancies, is not well understood.
We used serial serum samples from 71 pregnant women (25 primiparous, 25 multiparous, and 21 with two consecutive pregnancies) with natural, complication-free pregnancies and a healthy offspring at term who participated in a population-based screening trial for congenital infections in Finland between January 1st, 1988 and June 30, 1989 and provided a blood sample in each trimester.
Hormone levels were more strongly correlated between consecutive trimesters of a pregnancy than between the 1st and 3rd trimester (e.g., estradiol, rT1 vs. T2 = 0.51 and rT2 vs. T3 = 0.60, p < 0.01; rT1 vs. T3 = 0.32, p < 0.05). Concentrations of sRANKL remained stable throughout gestation, whereas estradiol, estrone, progesterone, testosterone, prolactin, and osteoprotegerin increased throughout pregnancy. First trimester hormone concentrations explained less of the variation in the third trimester on their own than second trimester hormone levels (e.g. estradiol R(2) T1 = 16 % and R(2) T2 = 42 %). Addition of maternal (e.g., smoking) and/or child characteristics (e.g., sex) improved the accuracy of the 3rd trimester estimates for some of the hormones.
One hormone measurement in early pregnancy, in conjunction with maternal and fetal characteristics, permits estimation of 3rd trimester hormone concentrations. Therefore, single hormone measurements available from maternity cohorts are suitable to quantify hormone exposure during pregnancy. To our knowledge, we provide the first data on correlations between hormone concentrations both across trimesters of a single pregnancy, as well as between two subsequent pregnancies.
Serological surveys of the prevalence of SARS-CoV-2 are instrumental to understanding the course of the COVID-19 epidemic. We evaluate the seroprevalence of SARS-CoV-2 among young adult Finnish ...females residing in 25 communities all over Finland from 2020 until 2022. Between 1.sup.st March 2020 and 30.sup.th June 2022, 3589 blood samples were collected from 3583 women born in 1992-95 when aged 25 or 28 years old attending the follow-up of an ongoing population-based trial of cervical screening strategies. The crude and population standardized SARS-CoV-2 seroprevalence was measured using nucleocapsid (induced by infection) and spike wild-type (WT) protein (induced both by infection and by vaccination) antigens over time and stratified by place of residence (inside or outside the Helsinki metropolitan region). During 2020 (before vaccinations), spike-WT and nucleocapsid IgG antibodies followed each other closely, at very low levels (<5%). Spike-WT seropositivity increased rapidly concomitant with mass vaccinations in 2021 and reached 96.3% in the 2.sup.nd quartile of 2022. Antibodies to nucleocapsid IgG remained relatively infrequent throughput 2020-2021, increasing rapidly in the 1.sup.st and 2.sup.nd quartiles of 2022 (to 19.7% and 56.6% respectively). The nucleocapsid IgG seropositivity increased more profoundly in participants residing in the Helsinki metropolitan region (4.5%, 8.4% and 43.9% in 2020, 2021 and 2022 respectively) compared to those residing in communities outside the capital region (4.5%, 4.3% and 34.7%). Low SARS-CoV-2 infection-related seroprevalence during 2020-2021 suggest a comparatively successful infection control. Antibodies to the SARS-CoV-2 WT spike protein became extremely common among young women by the end of 2021, in line with the high uptake of SARS-CoV-2 vaccination. Finally, the rapid increase of seroprevalences to the SARS-CoV-2 nucleocapsid protein during the first and second quartile of 2022, imply a high incidence of infections with SARS-CoV-2 variants able to escape vaccine-induced protection.
Infections with oncogenic human papillomaviruses (HPV) globally cause about 9% of cancers in females and 1% of cancers in males. HPV disease burden can be effectively controlled by prophylactic ...HPV-vaccination provided it has high impact.
A unique series of biobank-based and health registry-based studies that exploit randomized intervention cohorts has provided data on population-level safety of HPV vaccination, duration of vaccine-induced protection and impact of gender-neutral HPV vaccination, providing a scientific basis for policies to eradicate oncogenic HPV types and associated diseases worldwide.
The ultimate goal of HPV vaccination is the eradication of high-risk (hr) HPVs. Seventy-five percent coverage gender-neutral vaccination of early adolescents will rapidly eradicate also HPV16 from the general population.
Abstract
The elimination of cervical cancer rests on high efficacy of human papillomavirus (HPV) vaccines. The HPV type distribution among cases of invasive cervical cancer (ICC) is used to make ...predictions about the impact of eliminating different types of HPV, but accumulating evidence of differences in age-specific cancer incidence by HPV type exists. We used one of the largest population-based series of HPV genotyping of ICCs (n = 2,850; Sweden, 2002–2011) to estimate age-specific ICC incidence by HPV type and obtain estimates of the cancer-protective impact of the removal of different HPV types. In the base case, the age-specific ICC incidence had 2 peaks, and the standardized lifetime risk (SLTR, the lifetime number of cases per birth cohort of 100,000 females) for HPV-positive ICC was 651 per 100,000 female births. In the absence of vaccine types HPV 16 and HPV 18, the SLTR for ICC was reduced to 157 per 100,000 female births (24% of HPV-positive SLTR). Elimination of all 9 types that can currently be vaccinated against reduced the remaining SLTR to 47 per 100,000 female births (7%), the remaining ICC incidence only slowly increasing with age. In conclusion, after elimination of vaccine-protected HPV types, very few cases of ICC will be left, especially among fertile, reproductive-age women.
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