High-risk human papillomavirus status and prognosis in invasive cervical cancer: a nationwide cohort study. Dataset 2

SND-ID: snd1064-2. Version: 1.0. DOI: https://doi.org/10.5878/vc29-ft86

Citation

Creator/Principal investigator(s)

Pär Sparén - Karolinska Institutet, Department of Medical Epidemiology and Biostatistics orcid

Research principal

Karolinska Institutet - Department of Medical Epidemiology and Biostatistics rorId

Description

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,

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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 Show less..

Language

Method and outcome

Unit of analysis

Population

Women diagnosed as cervical cancer during year 2002-2011 in Sweden

Time Method

Sampling procedure

Biobank is connected to the study

Yes

Variables

4

Data format / data structure

Data collection
  • 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 spread

Geographic location: Sweden

Administrative information

Responsible department/unit

Department of Medical Epidemiology and Biostatistics

Funding 1

  • Funding agency: Swedish Research Council
  • Funding agency's reference number: 2014-03732; 2017-02346

Funding 2

  • Funding agency: Swedish Foundation for Strategic Research, SSF
  • Funding agency's reference number: KF10-0046; RB 13-0011

Funding 3

  • Funding agency: The Swedish Cancer Society
  • Funding agency's reference number: 110569; 140665

Ethics Review

Stockholm - Ref. 2011/1026-31/4, 2017/1028/32, 02- 189 556, 2012/1028/32, 2011/921-32

Topic and keywords

Research area

Medical and health sciences (Standard för svensk indelning av forskningsämnen 2011)

Health (CESSDA Topic Classification)

Publications

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: https://doi.org/10.1371/j

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Published: 2019-10-21
Last updated: 2019-10-21