Fig 1.
Age-standardized rates of CCA per 100000 women by country.
(A) Age-standardized point prevalence of CCA per 100,000 people in 2021, by country. (B) Age-standardized incidence rate of CCA per 100, 000 people in 2021, by country. (C) Age-standardized deaths rate of CCA per 100,000 people in 2021, by country. (D) Age-standardized DALY rate of CCA per 100,000 people in 2021, by country. Base map source: Natural Earth (public domain, CC0).
Fig 2.
Age-standardized rates trends of CCA per 100,000 women in different age groups.
(A) Global number of prevalent cases and prevalence of CCA per 100,000 women, by age in 2021. (B) Global number of incident cases and incidence of CCA per 100, 000 women, by age in 2021. (C) Global number of deaths and deaths rate of CCA per 100,000 women, by age in 2021. (D) Global number of DALYs and DALY rate of CCA per 100,000 women, by age in 2021. Lines indicate cases with 95% uncertainty intervals; dotted and dashed lines indicate 95% upper and lower uncertainty intervals.
Fig 3.
ASIR/ASDR of CCA for 21 regions and 204 countries and territories, by SDI, in 1990–2021.
(A) ASIR of CCA for 21 regions, by SDI, in 2021. (B) ASDR of CCA for 21 regions, by SDI, in 2021. Thirty points are plotted for each region and show the observed ASIR/ASDR from 1990 to 2021 for that region. (C) ASIR of CCA for 204 countries and territories, by SDI, in 2021. (D) ASDR of CCA for 204 countries and territories, by SDI, in 2021. Each point shows the observed ASIR/ASDR for each country in 2021. Black solid line shows the expected values based on SDI and disease rates in all locations. Regions or countries above the solid line represent a higher-than-expected burden and regions below the line show a lower-than-expected burden.
Fig 4.
Results of age–period–cohort (APC) model analysis.
(A) Annual percentage changes of the ASDR (net drift) and estimated age-specific local drifts. (B) Longitudinal age curves of female CCA deaths rates (per 100,000) adjusted for period effects. (C) Period rate ratios for death: adjusted for age and non-linear cohort effects by year. (D) Cohort rate ratios for death: adjusted for age and non-linear period effects. (E) Annual percentage changes of the ASIR (net drift) and estimated age-specific local drifts. (F) Longitudinal age curves of female CCA incidence rates (per 100,000) adjusted for period effects. (G) Period rate ratios for incidence: adjusted for age and non-linear cohort effects by year. (H) Cohort rate ratios for incidence: adjusted for age and non-linear period effects. RR > 1 indicates that the relative risk of death/incidence is higher for this birth period/cohort compared to the reference period/cohort. RR < 1 implies that the relative risk of death/incidence is lower for this birth period/cohort compared to the reference period/cohort.
Fig 5.
Bayesian age–period–cohort (BAPC) model–based projections of CCA.
(A) ASIR of HPV infection in women, 1990–2050. (B) ASDR attributable to HPV infection in women, 1990–2050.
Table 1.
Characteristics of VAERS reports of HPV vaccines in women, 2006–2025.
Fig 6.
Screening of safety signals for HPV vaccination.
Forest plot of PTs with a top 50 cases. The blue arrows indicate that the 95% confidence interval’s lower limit for ROR is above 50.
Fig 7.
Analysis of HPV Vaccine Reports and Google Search Trends.
(A) Number of HPV vaccine reports of VAERS and search popularity of the “HPV” topic on Google Trends. (B) Number of HPV vaccine reports of VAERS and search popularity of the “HPV vaccine” topic on Google Trends.
Fig 8.
Safety signals for vaccine administration differ by age.
(A) Forest plot of age-differentiated PT risk signals. (B) Volcano plot of different AEs between 9–17 years group and 18–26 years group receiving HPV vaccine injections. (C) Volcano plot of different AEs between 9–17 years group and 27–35 years group receiving HPV vaccine injections. (D) Volcano plot of different AEs between 9–17 years group and 36–45 years group receiving HPV vaccine injections. The horizontal coordinate shows the log2 ROR value, and the vertical coordinate indicates the adjusted p-value after log10 conversion. Significant signals are highlighted and annotated in prominent colors. P-values were adjusted using the Bonferroni correction method.