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- Lei, Jiayao, et al.
(författare)
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High-risk human papillomavirus status and prognosis in invasive cervical cancer : A nationwide cohort study
- 2018
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Ingår i: PLoS Medicine. - : PUBLIC LIBRARY SCIENCE. - 1549-1277 .- 1549-1676. ; 15:10
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Tidskriftsartikel (refereegranskat)abstract
- Background: High-risk human papillomavirus (hrHPV) infection is established as the major cause of invasive cervical cancer (ICC). However, whether hrHPV status in the tumor is associated with subsequent prognosis of ICC is controversial. We aim to evaluate the association between tumor hrHPV status and ICC prognosis using national registers and comprehensive human papillomavirus (HPV) genotyping.Methods and findings: In this nationwide population-based cohort study, we identified all ICC diagnosed in Sweden during the years 2002-2011 (4,254 confirmed cases), requested all archival formalin-fixed paraffin-embedded blocks, and performed HPV genotyping. Twenty out of 25 pathology bio-banks agreed to the study, yielding a total of 2,845 confirmed cases with valid HPV results. Cases were prospectively followed up from date of cancer diagnosis to 31 December 2015, migration from Sweden, or death, whichever occurred first. The main exposure was tumor hrHPV status classified as hrHPV-positive and hrHPV-negative. The primary outcome was all-cause mortality by 31 December 2015. Five-year relative survival ratios (RSRs) were calculated, and excess hazard ratios (EHRs) with 95% confidence intervals (CIs) were estimated using Poisson regression, adjusting for education, time since cancer diagnosis, and clinical factors including age at cancer diagnosis and International Federation of Gynecology and Obstetrics (FIGO) stage. Of the 2,845 included cases, hrHPV was detected in 2,293 (80.6%), and we observed 1,131 (39.8%) deaths during an average of 6.2 years follow-up. The majority of ICC cases were diagnosed at age 30-59 years (57.5%) and classified as stage IB (40.7%). hrHPV positivity was significantly associated with screen-detected tumors, young age, high education level, and early stage at diagnosis (p < 0.001). The 5-year RSR compared to the general female population was 0.74 (95% CI 0.72-0.76) for hrHPV-positive cases and 0.54 (95% CI 0.50-0.59) for hrHPV-negative cases, yielding a crude EHR of 0.45 (95% CI 0.38-0.52) and an adjusted EHR of 0.61 (95% CI 0.52-0.71). Risk of all-cause mortality as measured by EHR was consistently and statistically significantly lower for cases with hrHPV-positive tumors for each age group above 29 years and each FIGO stage above IA. The difference in prognosis by hrHPV status was highly robust, regardless of the clinical, histological, and educational characteristics of the cases. The main limitation was that, except for education, we were not able to adjust for lifestyle factors or other unmeasured confounders.Conclusions: In this study, women with hrHPV-positive cervical tumors had a substantially better prognosis than women with hrHPV-negative tumors. hrHPV appears to be a biomarker for better prognosis in cervical cancer independent of age, FIGO stage, and histological type, extending information from already established prognostic factors. The underlying biological mechanisms relating lack of detectable tumor hrHPV to considerably worse prognosis are not known and should be further investigated.
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| 2. |
- Lei, Jiayao, et al.
(författare)
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HPV vaccination and the risk of invasive cervical cancer
- 2020
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Ingår i: New England Journal of Medicine. - 0028-4793 .- 1533-4406. ; 383:14, s. 1340-1348
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND The efficacy and effectiveness of the quadrivalent human papillomavirus (HPV) vaccine in preventing high-grade cervical lesions have been shown. However, data to inform the relationship between quadrivalent HPV vaccination and the subsequent risk of invasive cervical cancer are lacking. METHODS We used nationwide Swedish demographic and health registers to follow an open population of 1,672,983 girls and women who were 10 to 30 years of age from 2006 through 2017. We assessed the association between HPV vaccination and the risk of invasive cervical cancer, controlling for age at follow-up, calendar year, county of residence, and parental characteristics, including education, household income, mother’s country of birth, and maternal disease history. RESULTS During the study period, we evaluated girls and women for cervical cancer until their 31st birthday. Cervical cancer was diagnosed in 19 women who had received the quadrivalent HPV vaccine and in 538 women who had not received the vaccine. The cumulative incidence of cervical cancer was 47 cases per 100,000 persons among women who had been vaccinated and 94 cases per 100,000 persons among those who had not been vaccinated. After adjustment for age at follow-up, the incidence rate ratio for the comparison of the vaccinated population with the unvaccinated population was 0.51 (95% confidence interval [CI], 0.32 to 0.82). After additional adjustment for other covariates, the incidence rate ratio was 0.37 (95% CI, 0.21 to 0.57). After adjustment for all covariates, the incidence rate ratio was 0.12 (95% CI, 0.00 to 0.34) among women who had been vaccinated before the age of 17 years and 0.47 (95% CI, 0.27 to 0.75) among women who had been vaccinated at the age of 17 to 30 years. CONCLUSIONS Among Swedish girls and women 10 to 30 years old, quadrivalent HPV vaccination was associated with a substantially reduced risk of invasive cervical cancer at the population level.
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| 4. |
- Lei, Jiayao
(författare)
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Prevention and prognosis of cervical cancer : the interplay of human papillomavirus, vaccination and screening
- 2020
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Human papillomavirus (HPV) is the major cause of cervical cancer. The well-established natural history from HPV infection to the occurrence of invasive cervical cancer serves as the basis for prevention of cervical cancer through prophylactic HPV vaccination (primary prevention) and cervical screening (secondary prevention). Cervical cancer detected through screening also has better chances of being cured than cancers not detected through screening. This thesis addresses research questions on prevention and prognosis of cervical cancer within the framework of the interplay of HPV, vaccination, and cervical screening, and it also provides insights for evidence-based decision-making. In Paper I, we examined the association between cervical screening with cytology and risk of adenosquamous cell carcinoma (ASC) and rare histological types of invasive cervical carcinoma (RICC). Based on a nationwide cervical cancer Audit, we conducted a nested case- control study including 338 cases of ASC and RICC diagnosed during 2002-2011 in Sweden with their year-of-birth-matched controls. We found that screening with cytology was associated with decreased risk of ASC and RICC, but the magnitude of risk reduction in relation to cervical screening was less for RICC than for ASC. The majority of ASC and RICC cases were positive for high-risk HPV in tumor tissues. In Paper II, we evaluated whether the tumor high-risk human papillomavirus (hrHPV) status was associated with the prognosis of cervical cancer. In a nationwide population-based study, we included 2845 primary invasive cervical cancer cases diagnosed in Sweden during 2002– 2011, and comprehensively tested diagnostic blocks for 13 hrHPV types and 24 HPV types which were not established as oncogenic. Women with hrHPV-positive cervical tumors had a substantially better prognosis (39% lower excess mortality) than women with hrHPV-negative tumors. The difference of prognosis by tumor hrHPV status remained statistically significant, irrespective of age, cancer stage, and histological type. In Paper III, we investigated screening performance in terms of positive predictive value (PPV) of cytology for cervical intraepithelial neoplasia grade 2 or worse (CIN2+) among HPV- vaccinated birth cohorts. Using a population-based cohort design, we included women born 1989-1993 who were resident in Sweden since the introduction of HPV vaccination and attended cervical screening at age 23, based on records from Swedish National Cervical Screening Registry (NKCx). We found that vaccinated women had lower PPV of cytology for CIN2+ compared to unvaccinated women. The decrease in PPV was greater among women vaccinated before age 17 than those vaccinated at age 17-22. In Paper IV, we assessed the association between HPV vaccination and the risk of invasive cervical cancer in a population-based cohort study. An open cohort of women aged 15-30 (including age 30) living in Sweden were included and followed during 2006-2017 for HPV vaccination and first occurrence of invasive cervical cancer. The findings showed that HPV vaccination was related to a 52% lower risk of invasive cervical cancer for vaccinated women compared to unvaccinated women. Younger age at vaccination initiation was associated with a more pronounced risk reduction (83% risk reduction when vaccinated before age 17). In conclusion, this thesis shows that cervical screening can effectively reduce the risk of ASC and RICC, which is beyond the established evidence on preventing squamous cell carcinoma and adenocarcinoma. HPV vaccination can effectively reduce the risk of cervical cancer; the ultimate goal of cervical cancer prevention. With the implementation of HPV vaccination, the PPV of cytology for CIN2+ has decreased in vaccinated women compared to unvaccinated women, especially among those vaccinated at younger age. Tumor hrHPV status is associated with the prognosis of cervical cancer, which could add value to the clinically established prognostic factors. Taken together, these studies add knowledge to the current understanding of cervical cancer prevention strategies and prognosis of cervical cancer, and serve as a basis for evidence-based decision-making and policy changes in the future.
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| 5. |
- Wang, Jiangrong, et al.
(författare)
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Cervical cancer case-control audit : Results from routine evaluation of a nationwide cervical screening program
- 2020
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Ingår i: International Journal of Cancer. - : WILEY. - 0020-7136 .- 1097-0215. ; 146:5, s. 1230-1240
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Tidskriftsartikel (refereegranskat)abstract
- Our study used a refined case-control cervical cancer Audit framework to investigate effectiveness of cervical screening, with measures of three screening failures: irregular-participation, cervical cancer developed after cytological abnormalities and after normal screening results. The register-based study included 4,254 cervical cancer cases diagnosed in Sweden during 2002-2011, and 30 population-based controls per case. We used conditional logistic regression models to examine relative risks of cervical cancer in relation to screening participation and screening results in the past two screening rounds from 6 months before cancer diagnosis. We found that women unscreened in past two screening rounds showed four times increased risk of cervical cancer compared to women screened in time (OR = 4.1, 95% CI = 3.8-4.5), and women unscreened in the previous round but screened in the most recent round also showed a statistically significantly elevated risk (OR = 1.6, 95% CI = 1.5-1.8). Women having abnormality in previous two rounds exhibited higher risk of cervical cancer compared to women screened with normal results, while having normal results in the subsequent round after the abnormality also yielded an increased risk (OR = 4.0, 95% CI = 3.2-5.1). Being screened with only normal results was associated with 89% risk reduction for squamous cell cancer, compared to women unscreened, but only 60% reduction for adenocarcinoma. Our findings emphasize the importance of routine participation in cervical screening and suggest that management of abnormalities, as well as sensitivity of the test, warrants improvement especially for preventing cervical adenocarcinoma. The Audit framework serves as routine evaluation model and the findings benchmark for future evaluation of changes in screening practice.
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