High-risk human papillomavirus status and prognosis in invasive cervical cancer: a nationwide cohort study. Dataset 2
https://doi.org/10.5878/vc29-ft86
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.
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 biobanks 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.
In conclusion, 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.
Purpose:
To compile a comprehensive survival and HPV genotyping data and provide a large-scale population-based evaluation of the association between tumor high risk HPV status and prognosis of invasive cervical cancer.
This is an aggregated dataset (popmort_agg_2000_2015.dta) including the average survival rates of the Swedish female population, by age, for years 2000-2015. The dataset is generated based on the age-, gender- and calender year- specific survival rates of the Swedish population during the same calendar period.
The dataset included 4 variables:
• Sex: Gender (all female): 2=female.
• _age: Age (in years)
• _year: Calendar year
• Prob: Survival probability in corresponding age and calendar year
Citation and access
Citation and access
Data access level:
Creator/Principal investigator(s):
Research principal:
Data contains personal data:
No
Citation:
Language:
Method and outcome
Method and outcome
Unit of analysis:
Population:
Women diagnosed as cervical cancer during year 2002-2011 in Sweden
Time method:
Sampling procedure:
Variables:
4
Data format/data structure:
Data collection - Observation
Data collection - Observation
Mode of collection:
Observation
Time period(s) for data collection:
2000-01-01 - 2015-12-31
Data collector:
- Karolinska Institutet
Source of the data:
- Population group
- Biological samples
Geographic coverage
Geographic coverage
Geographic location:
Administrative information
Administrative information
Responsible department/unit:
Department of Medical Epidemiology and Biostatistics [C8]
Ethical Review
Ethical Review
Reviewer:
- Stockholm Ethical Review Board
Registration number:
2011/1026-31/4, 2017/1028/32, 02- 189 556, 2012/1028/32, 2011/921-32
Funding
Funding
Funding agency:
- The Swedish Cancer Society
Award number:
110569; 140665
Funding agency:
- Swedish Foundation for Strategic Research, SSF
Award number:
KF10-0046; RB 13-0011
Funding agency:
- Swedish Research Council
Opens a new window at ror.org.
ROR
Award number:
2014-03732_VR
Award title:
Nationwide audit of cervical screening in Sweden
Funding information:
The main purpose of this proposed study is to perform a comprehensive population-based evaluation of strengths and weaknesses of the currently used preventive strategies for cervical cancer (so-called Audit). Cervical cancer morbidity and mortality will be evaluated in relation to the performance of the current Swedish cervical screening program, and we will set a benchmark for the evaluation of new screening methods with HPV based screening and for HPV vaccination. With large-scale HPV-typing of all cervical cancer tumors in Sweden during the years 2002-2011 we will create a nation-wide baseline of type-specific HPV prevalence, by age and histo-pathological type, as well as detailed screening history that will be gathered from the National Quality Register for Cervical Cancer Prevention, encompassing up to 40 years of screening experience in Sweden. Ten controls acquired from the Total Population Register will be assigned to each case, and data from the Quality Register will be linked to controls as well. The results gained from this study will be obtained from a real-life, nation-wide, clinical cancer population, and will therefore be of considerably high validity that is rarely available from scientific studies. A complete set of all cervical cancers diagnosed during a decade in Sweden lacks comparison internationally and would indeed serve as a rarely-seen initiative. The results will be applicable to real-life screening practices within the near future.
Funding agency:
- Swedish Research Council
Opens a new window at ror.org.
ROR
Award number:
2017-02346_VR
Award title:
Register- and Biobank-based Optimization of Cervical Cancer Prevention
Funding information:
Major advances in the understanding of the infectious etiology of cervical cancer have provided highly promising new prevention tools that require diligent implementation and evaluation to achieve eradication of cervical cancer. Our research team has spent more than a decade developing a national database for advancing research on cervical cancer prevention through leveraging health registers and biobanks, collecting clinical data, and developing the Swedish National Cervical Screening Registry. Using detailed clinical, screening, and microbiological data, we will: a) Perform a comprehensive population-based evaluation of strengths and weaknesses of current preventive strategies for cervical cancer (Case-Control Audit) as a benchmark for new prevention tools; b) Perform an internationally leading evaluation of the effectiveness of the Swedish HPV vaccination program, in terms of clinical effectiveness, costs, and safety; c) Utilize mathematical simulation models to evaluate new national guidelines for primary HPV screening and the intersection of screening with HPV vaccination, as well as assessing the cost-effectiveness of various prevention strategies. The results of our research program will aid clinicians and policy makers in Sweden and provide an example for efficient and comprehensive evaluation of prevention strategies internationally. The results will have an immediate impact on women at risk of cervical cancer and will be applicable to real-life prevention programs.
Topic and keywords
Topic and keywords
CESSDA topic classification:
Swedish Standard Classification of Research Subjects 2025:
Keywords:
Relations
Relations
Is obsoleted by:
Publications
Publications
Citation:
Lei J, Ploner A, Lagheden C, Eklund C, Nordqvist Kleppe S, Andrae B, Elfström KM, Dillner J, Sparén P, Sundström K (2018). High-risk human papillomavirus status and prognosis in invasive cervical cancer: A nationwide cohort study. PLoS Med 15(10): e1002666. DOI: 10.1371/journal.pmed.1002666
DOI:
Metadata
Metadata
Version 1.0
