| 1. |
- Lei, Jiayao, et al.
(author)
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HPV vaccination and the risk of invasive cervical cancer
- 2020
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In: New England Journal of Medicine. - 0028-4793 .- 1533-4406. ; 383:14, s. 1340-1348
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Journal article (peer-reviewed)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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| 2. |
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| 3. |
- Sundström, Karin, et al.
(author)
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Follow-up of women with cervical cytological abnormalities showing atypical squamous cells of undetermined significance or low-grade squamous intraepithelial lesion : a nationwide cohort study
- 2017
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In: American Journal of Obstetrics and Gynecology. - : MOSBY-ELSEVIER. - 0002-9378 .- 1097-6868. ; 216:1
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Journal article (peer-reviewed)abstract
- BACKGROUND: Atypical squamous cells of undetermined significance or low-grade squamous intraepithelial lesion in abnormal cervical cytology among young women in cervical cancer screening is an increasing health burden, and comparative effectiveness studies of different management options for such diagnoses are needed. OBJECTIVE: The objective of the study was to compare the incidence of invasive cervical cancer, following different management options pursued after an atypical squamous cells of undetermined significance/low-grade squamous intraepithelial lesion index smear. STUDY DESIGN: In this nationwide cohort study, we included all women aged 22-50 years and resident in Sweden 1989-2011 and with at least 1 cervical smear registered during the study period ( n = 2,466,671). Followup of a first atypical squamous cells of undetermined significance/low-grade squamous intraepithelial lesion cytological diagnosis within 25 months was classified as repeat cytology, colposcopy/biopsy, or without further assessment. Incidence rate ratios and 95% confidence intervals of subsequent cervical cancer within 6.5 years following atypical squamous cells of undetermined significance/low-grade squamous intraepithelial lesion were estimated using Poisson regression by age group and management strategy. RESULTS: Women managed with repeat cytology within 6 months after atypical squamous cells of undetermined significance or low-grade squamous intraepithelial lesion cytology had a similar risk of cervical cancer compared with colposcopy/biopsy ( incidence rate ratio, 1.1, 95% confidence interval, 0.5-2.5, and incidence rate ratio, 2.0, 95% confidence interval, 0.6-6.5, respectively) among women aged 22-27 years. For women aged 28 years and older, women managed with repeat cytology had a higher risk for cervical cancer than women managed with colposcopy/biopsy. CONCLUSION: Our findings suggest that women with a first cytological diagnosis of atypical squamous cells of undetermined significance/low-grade squamous intraepithelial lesion up to age 27 years may indeed be safely followed up with repeat cytology within 6 months. A large amount of colposcopies that are currently performed in this group, therefore, could safely be discontinued.
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| 4. |
- Wang, Jiangrong, et al.
(author)
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Cervical cancer case-control audit : Results from routine evaluation of a nationwide cervical screening program
- 2020
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In: International Journal of Cancer. - : WILEY. - 0020-7136 .- 1097-0215. ; 146:5, s. 1230-1240
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Journal article (peer-reviewed)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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| 5. |
- Wang, Jiangrong
(author)
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Effectiveness and equity of cervical cancer prevention : real-life evidence from organised programmes in Sweden
- 2017
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Doctoral thesis (other academic/artistic)abstract
- Cervical cancer incidence has substantially declined since cervical screening was implemented five decades ago. The long-term hope of eliminating cervical cancer is promising with the development of effective Human papillomavirus (HPV) vaccines. Optimising effectiveness and promoting high and equal uptake of preventive approaches are essential for achieving this goal. This thesis aimed to use register data in Sweden to perform in-depth evaluation of the effectiveness of cervical screening and investigate the factors associated with HPV vaccine uptake. The work focused in detail upon the uncertain preventive effect against cervical adenocarcinoma in relation to the finding of glandular abnormalities in screening, the effectiveness of screening for the conspicuous incidence of cervical cancer at older ages, as well as social disparity of HPV vaccine uptake in different modes of vaccination delivery. Effectiveness of cervical screening in preventing invasive cervical cancer has been reported under a case-control audit framework in Sweden, based on cervical cancer cases diagnosed in 1999-2001. Yet, assessing long-term screening history and controlling for confounding factors were hampered by unavailable data, and statistical power was limited to stratify the evaluation by histopathological type. We therefore performed an updated case-control audit based on cervical cancer cases diagnosed in 2002-2011 (Study III), to examine the risk of invasive cervical cancer in relation to screening history in the past two screening rounds, adjusted for education and stratified by the two main histopathological types. We found that non-routine participation to cervical screening was associated with increased risk of invasive cervical cancer. Having an abnormality in previous two screening rounds was associated with elevated risk, particularly if not being screened in the subsequent screening round after an abnormality. The lower effectiveness of cervical screening in preventing adenocarcinoma compared to squamous cell carcinoma resulted from both lower assurance from normal screening results, and higher risk following abnormalities. These findings reinforce the evidence of the cancer-preventive effect of cervical screening and emphasise the importance of routine participation in screening. We also identify relative weaknesses of the screening programme that would guide future research to address improvement. Atypical glandular cells (AGC) found in cervical screening is a cytological abnormality of the same type of cells giving rise to cervical adenocarcinoma. However, the long-term risk of cervical cancer following AGC has not been comprehensively investigated due to its rarity. We used the Swedish National Cervical Screening Registry (NKCx) to identify all AGC diagnosed in cervical screening from 1980-2011, examined the risk of cervical cancer by histopathological type for up to 15 years, and compared the subsequent histological assessment and risk of cancer to that after high-grade squamous intraepithelial neoplasia (HSIL) (Study I). We found that AGC was associated with a moderate-high proportion of prevalent cancer, and a high long-term risk of incident cervical cancer, especially adenocarcinoma. Only 54% of AGC were followed by histology within six months, and among those being followed with histology, the cancer incidence after AGC was still statistically significantly higher than that after HSIL. Our findings confirm the considerable risk associated with AGC and revealed suboptimal management following this specific abnormality. We highlight one of the deeper causes of unsatisfactory preventive effects of screening against cervical adenocarcinoma, and the necessity of improving management practice for AGC. Cervical cancer is generally associated with middle-aged women, but the first Swedish case-control audit revealed that cervical cancer in women over 60 years of age accounted for more than one-third of annual cervical cancer cases. Data from other Nordic countries have also exhibited similar to higher incidence of cervical cancer among older-aged women compared to middle-aged women, leading to uncertainty on the underlying reason of biological or screening effect and the effectiveness of cervical screening after age 60. Therefore, we used NKCx and the Swedish Cancer Registry to investigate the risk of cervical cancer from age 61-80 years by screening history at ages 51-60 years, and evaluated the effectiveness of cervical screening at ages 61-65 stratified by screening history (Study II). We found that screening at ages 61-65 was associated with substantial risk reduction up to age 80 in women unscreened or having abnormalities in their 50s. Yet in women screened with normal results in their 50s, the subsequent risk of cervical cancer was remarkably lower than that in women unscreened or having abnormalities in the past, and in these women screening after age 60 was not associated with any statistically significant risk reduction. Our results should inform the current debate regarding when and how to discontinue cervical screening in older-aged women. HPV vaccines have been available worldwide since 2006-2007. Their efficacy and effectiveness in preventing cervical precursor lesions have been shown repeatedly. Pursuing high and equal coverage of HPV vaccination is the common goal to reduce inequality of cervical cancer development in the future. Various modes of delivery of HPV vaccination were implemented worldwide and in Sweden. We used Swedish vaccination registers and social-demographic registers to examine girls’ HPV vaccine uptake in relation to parental country of birth, education and family income, by three delivery modes of HPV vaccination (Study IV). We found that free-of-charge school-based delivery achieved the highest uptake of HPV vaccination with the lowest social disparity, suggesting the importance of reducing individual payment and providing easy access to promote equality of cervical cancer prevention. In conclusion, this thesis confirms the overall effectiveness of cervical screening in preventing invasive cervical cancer, addresses specific questions regarding unsatisfactory prevention for cervical adenocarcinoma and cervical cancer in older women, as well as identifies suboptimal aspects in screening for further investigation. It optimises the audit framework as an evaluation tool for screening programme quality assurance, and provides a benchmark for future comparisons with new screening practices. The thesis also verifies the role of delivery mode of HPV vaccination on reaching high and equal uptake of the vaccine, bolstering the hope of ultimate elimination of cervical cancer.
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| 6. |
- Wang, Jiangrong, et al.
(author)
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Effectiveness of cervical screening after age 60 years according to screening history : Nationwide cohort study in Sweden
- 2017
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In: PLoS Medicine. - : Public Library of Science (PLoS). - 1549-1277 .- 1549-1676. ; 14:10
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Journal article (peer-reviewed)abstract
- Background The relatively high incidence of cervical cancer in women at older ages is a continuing concern in countries with long-established cervical screening. Controversy remains on when and how to cease screening. Existing population-based studies on the effectiveness of cervical screening at older ages have not considered women's screening history. We performed a nationwide cohort study to investigate the incidence of cervical cancer after age 60 years and its association with cervical screening at age 61-65, stratified by screening history at age 51-60. Methods and findings Using the Total Population Register, we identified 569,132 women born between 1 January 1919 and 31 December 1945, resident in Sweden since age 51. Women's cytological screening records, cervical cancer occurrence, and FIGO stage (for those diagnosed with cancer) were retrieved from national registers and medical charts. We calculated the cumulative incidence of cervical cancer from age 61 to age 80 using a survival function considering competing risk, and estimated the hazard ratio (HR) of cervical cancer in relation to screening status at age 61-65 from Cox models, adjusted for birth cohort and level of education, conditioning on women's screening history in their 50s. In women unscreened in their 50s, the cumulative incidence up to age 80 was 5.0 per 1,000 women, and screening at age 61-65 was associated with a lower risk for cervical cancer (HR = 0.42, 95% CI 0.24-0.72), corresponding to a decrease of 3.3 cancer cases per 1,000 women. A higher cumulative incidence and similarly statistically significant risk decrease was seen for women with abnormal smears in their 50s. In women adequately or inadequately screened with only normal results between age 51 and age 60, the cumulative incidence of cervical cancer from age 61 to 80 was 1.6 and 2.5 per 1,000 women, respectively, and further screening at age 61-65 was not associated with statistically significant decreases of cervical cancer risk up to age 80, but with fewer cancer cases of advanced stages at age 61-65. Adjustment for potential lifestyle confounders was limited. Conclusions In this study, cervical screening with cytology at age 61-65 was associated with a statistically significant reduction of subsequent cervical cancer risk for women who were unscreened, or screened with abnormalities, in their 50s. In women screened with normal results in their 50s, the risk for future cancer was not sizeable, and the risk reduction associated with continued screening appeared limited. These findings should inform the current debate regarding age and criteria to discontinue cervical screening.
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| 7. |
- Wang, Jiangrong, et al.
(author)
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Increase of cervical cancer incidence in Sweden in relation to screening history : population cohort study
- 2020
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In: Acta Oncologica. - : TAYLOR & FRANCIS LTD. - 0284-186X .- 1651-226X. ; 59:8, s. 988-993
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Journal article (peer-reviewed)abstract
- Background: Cervical cancer incidence in Sweden decreased from 24/100,000 in 1965 to 8/100,000 in 2011, but has from 2014 increased to 11/100,000. The increase appears to correlate to screening history. We perform a study of the cancer risk change in relation to screening history over two screening rounds to verify the correlation. Material and methods: We studied the cohorts of all 3,047,850 individual women living in Sweden in each year from 2002-2015. Registry linkages between the Total Population Register, the Swedish National Cervical Screening Registry, the Swedish Cervical Cancer Audit database and the National Quality Register for Gynecological Cancer, defined the incidence rates of invasive cervical cancer comparing time periods 2002-2013 to 2014-2015, in women whose screening history in 2 screening intervals prior to each year were either (i) adequately screened with normal results (almost exclusively cytology, 52% of the population) or (ii) unscreened (13% of the population). We also investigated the incidence increase by time since a normal smear performed in 2002-2012. Results: Among women adequately screened with normal results there was a strong incidence increase in 2014-2015 compared to previous years (Incidence rate ratio (IRR) = 1.59, 95%CI = 1.36-1.85), but no significant increase among unscreened women (IRR = 1.09, 95%CI = 0.94-1.27). There was no increase in incidence 0-2.5 years after a normal smear over the study period (IRR = 1.04, 95% CI = 0.88-1.24), but a strong increase 3-4 years after a normal smear since year 2009 (IRR = 1.52, 95% CI = 1.25-1.84). Conclusion: The results suggest that the overall increase is associated with an increased cancer risk in women adequately screened with normal cytological results. Possibly, precursor lesions missed in one screening round might result in detection of early stage invasive cancer in the subsequent screening.
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| 8. |
- Wang, Jiangrong, et al.
(author)
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Long-term follow-up of cervical cancer incidence after normal cytological findings
- 2024
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In: INTERNATIONAL JOURNAL OF CANCER. - 0020-7136 .- 1097-0215. ; 154:3, s. 448-453
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Journal article (peer-reviewed)abstract
- An increase in cervical cancer incidence in Sweden from 2014 to 2015 has been attributed to an increase in false-negative cytological findings before cancer diagnoses. Years later, we performed a long-term follow-up to investigate whether the problem persisted. At each calendar year from 2016 to 2020, we identified women with prior normal cervical screening results through linkage to the Swedish National Cervical Screening Registry. We reported their incidence rates (IRs) of invasive cervical cancer in consecutive years and compared the IRs over time. For the years 2016 to 2020, there was no overall change in cervical cancer incidence after two normal cytology in the last two screening intervals. However, there was a further 62% increase among women 50 to 60 years of age with normal cytology in the past two screening intervals. The incidence rate of cervical cancer was high among nonscreened women and low among HPV-screened women with negative results, with no trends over time. Our results imply that the previously reported decrease in sensitivity of cervical cytology is persisting. Although primary cytology screening is no longer used, cytology is used in triaging among HPV-positive women. Our findings suggest that improved triaging is needed, for example, improved quality assurance and/or use of alternative triage tests.
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| 9. |
- Wang, Jiangrong, et al.
(author)
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Mode of HPV vaccination delivery and equity in vaccine uptake : A nationwide cohort study
- 2019
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In: Preventive Medicine. - : Elsevier BV. - 0091-7435 .- 1096-0260. ; 120, s. 26-33
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Journal article (peer-reviewed)abstract
- Ten years after its introduction, equity in human papillomavirus (HPV) vaccine uptake remains unattained, not least for the groups at highest risk of cervical cancer. In Sweden, three different delivery modes of the vaccine have been in effect since May 2007. We used this as a natural experiment to investigate girls’ HPV vaccine uptake in relation to parental country of birth and socioeconomic characteristics, by mode of delivery. Our nationwide study cohort comprised 689,676 girls born between 1990 and 2003. Data on HPV vaccination of the girls and parental birth/socioeconomic characteristics were retrieved from national registers. We examined the association between girls’ vaccine uptake and parental characteristics, stratified by mode of delivery. The cumulative uptake of at least one dose of HPV vaccine was 37%, 48% and 79% for subsidised opportunistic, free-of-charge catch-up outside-school and free-of-charge school-based vaccination, respectively. In the subsidised vaccination, having parents born outside of Sweden, with low education and low family income was strongly associated with lower uptake [HR (95% confidence interval (CI)) = 0.49 (0.48–0.50), 0.32 (0.31–0.33), 0.53 (0.52–0.54), respectively]. The associations were partially reduced in catch-up outside-school, and strongly reduced in school-based vaccination delivery [HR (95% CI) =0.82 (0.81–0.83), 0.92 (0.91–0.94), 0.87 (0.85–0.88), respectively]. Free-of-charge school-based HPV vaccination achieved the highest uptake and displayed the least disparity in country of birth and socioeconomic background of the parents. This appears to be the most effective and equitable delivery mode for reaching high population vaccination coverage, including high-risk groups for cervical cancer.
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| 10. |
- Wang, Jiangrong, et al.
(author)
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Risk of invasive cervical cancer after atypical glandular cells in cervical screening : nationwide cohort study
- 2016
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In: BMJ-BRITISH MEDICAL JOURNAL. - : BMJ. - 1756-1833. ; 352
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Journal article (peer-reviewed)abstract
- OBJECTIVES To investigate the risks of invasive cervical cancer after detection of atypical glandular cells (AGC) during cervical screening. DESIGN Nationwide population based cohort study. SETTING Cancer and population registries in Sweden. PARTICIPANTS 3 054 328 women living in Sweden at any time between 1 January 1980 and 1 July 2011 who had any record of cervical cytological testing at ages 23-59. Of these, 2 899 968 women had normal cytology results at the first screening record. The first recorded abnormal result was atypical glandular cells (AGC) in 14 625, high grade squamous intraepithelial lesion (HSIL) in 65 633, and low grade squamous intraepithelial lesions (LSIL) in 244 168. MAIN OUTCOME MEASURES Cumulative incidence of invasive cervical cancer over 15.5 years; proportion of invasive cervical cancer within six months of abnormality (prevalence); crude incidence rates for invasive cervical cancer over 0.5-15.5 years of follow-up; incidence rate ratios compared with women with normal cytology, estimated with Poisson regression adjusted for age and stratified by histopathology of cancer; distribution of clinical assessment within six months after the abnormality. RESULTS The prevalence of cervical cancer was 1.4% for women with AGC, which was lower than for women with HSIL (2.5%) but higher than for women with LSIL (0.2%); adenocarcinoma accounted for 73.2% of the prevalent cases associated with AGC. The incidence rate of invasive cervical cancer after AGC was significantly higher than for women with normal results on cytology for up to 15.5 years and higher than HSIL and LSIL for up to 6.5 years. The incidence rate of adenocarcinoma was 61 times higher than for women with normal results on cytology in the first screening round after AGC, and remained nine times higher for up to 15.5 years. Incidence and prevalence of invasive cervical cancer was highest when AGC was found at ages 30-39. Only 54% of women with AGC underwent histology assessment within six months, much less than after HSIL (86%). Among women with histology assessment within six months, the incidence rate of cervical cancer after AGC was significantly higher than that after HSIL for up to 6.5 years. CONCLUSIONS AGC found at cervical screening is associated with a high and persistent risk of cervical cancer for up to 15 years, particularly for cervical adenocarcinoma and women with AGC at age 30-39. Compared with the reduction in risk of cancer seen after HSIL management, management of AGC seems to have been suboptimal in preventing cervical cancer. Research to optimise management is needed, and a more aggressive assessment strategy is warranted.
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