Intended for healthcare professionals

  1. Research
  2. Cervical screening and...
  3. Cervical screening and risk of adenosquamous and rare histological types of invasive cervical carcinoma: population based nested case-control study
CCBYNC Open access
Research

Cervical screening and risk of adenosquamous and rare histological types of invasive cervical carcinoma: population based nested case-control study

BMJ 2019; 365 doi: https://doi.org/10.1136/bmj.l1207 (Published 03 April 2019) Cite this as: BMJ 2019;365:l1207
  1. Jiayao Lei, postgraduate student1,
  2. Bengt Andrae, senior consultant1 2,
  3. Alexander Ploner, statistician1,
  4. Camilla Lagheden, biomedical scientist3,
  5. Carina Eklund, biomedical scientist3,
  6. Sara Nordqvist Kleppe, database administrator1 3,
  7. Jiangrong Wang, postdoctoral researcher1 3,
  8. Fang Fang, senior researcher1,
  9. Joakim Dillner, professor3 4,
  10. K Miriam Elfström, research associate3 5,
  11. Pär Sparén, professor1
  1. 1Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, 171 77 Stockholm, Sweden
  2. 2Center for Research and Development, Uppsala University/Region of Gävleborg, 801 88 Gävle, Sweden
  3. 3Department of Laboratory Medicine, Karolinska Institutet, 141 83 Stockholm, Sweden
  4. 4Karolinska University Laboratory, Karolinska University Hospital, 171 76 Stockholm, Sweden
  5. 5Regional Cancer Center Stockholm-Gotland, 118 27 Stockholm, Sweden
  1. Correspondence to: J Lei jiayao.lei{at}ki.se (or @JiayaoL on Twitter)
  • Accepted 11 March 2019

Abstract

Objectives To examine the association of cervical cytology screening with the risk of adenosquamous cell carcinoma (ASC) and rare histological types of invasive cervical carcinoma (RICC), using comprehensive registry data, and to assess tumour human papillomavirus status of ASC and RICC.

Design Nationwide, population based, nested case-control study.

Setting Sweden.

Participants All cases of invasive cervical carcinoma in Sweden during 2002-11 (4254 confirmed cases after clinical and histopathological review). 338 cases were neither squamous cell carcinoma nor adenocarcinoma, including 164 cases of ASC and 174 cases of RICC (glassy cell carcinoma, clear cell carcinoma, small cell carcinoma, neuroendocrine cell carcinoma, large cell carcinoma, and undifferentiated carcinoma). 30 birth year matched controls from the general Swedish population were matched to each case by applying incidence density sampling.

Main outcome measures Conditional logistic regression was used to calculate odds ratios, interpreted as incidence rate ratios, for risk of ASC and RICC in relation to screening status and screening history, adjusted for education. Human papillomavirus distribution of ASC and RICC was based on available archival tumour tissues from most Swedish pathology biobanks.

Results Women with two screening tests in the previous two recommended screening intervals had a lower risk of ASC (incidence rate ratio 0.22, 95% confidence interval 0.14 to 0.34) and RICC (0.34, 0.21 to 0.55), compared with women without any test. High risk human papillomavirus was detected in 148/211 (70%) cases with valid human papillomavirus results from tumour tissues. The risk reduction among women with tumours that were positive (incidence rate ratio 0.28, 0.18 to 0.46) and negative (0.27, 0.13 to 0.59) for high risk human papillomavirus was similar, compared with women who did not attend any test.

Conclusions Cervical screening is associated with reduced risk of ASC and RICC, and most ASC and RICC are positive for high risk human papillomavirus. This evidence provides a benchmark for evaluating future cervical screening strategies.

Footnotes

  • Contributors: JL did the literature search and review. BA, JD, and PS conceived the research questions and hypotheses and designed the study. PS, JD, and SNK collected diagnostic samples. BA reviewed medical charts and supported histopathological classification of all cases. CL and CE did the laboratory analysis on human papillomavirus genotyping and validation. JL and AP did statistical analysis, and JL, BA, AP, JD, FF, KME, and PS interpreted the data. JL wrote the original draft of this manuscript. All authors were involved in the critical revision of article and have read and approved submission of the manuscript. The corresponding author attests that all listed authors meet authorship criteria and that no others meeting the criteria have been omitted. PS is the guarantor.

  • Funding: This work was supported by the Swedish Foundation for Strategic Research (KF10-0046 and RB13-0011), the Swedish Cancer Society (11 0569, 14 0665, and 16 0699), the Swedish Research Council (2014-03732 and 2017-02346), the China Scholarship Council (201507930001), and the Centre for Research and Development, Uppsala University/Region of Gävleborg. The study sponsors did not participate in study design, data collection, analysis, interpretation of data, writing of the article, or the decision to submit it for publication.

  • Competing interests: All authors have completed the ICMJE uniform disclosure form at www.icmje.org/coi_disclosure.pdf (available on request from the corresponding author) and declare: JD has obtained grants to his institution from Roche and Genomica for research on human papillomavirus tests; no financial relationships with any organisations that might have an interest in the submitted work in the previous three years; no other relationships or activities that could appear to have influenced the submitted work.

  • Ethical approval: This study was approved by the Regional Ethical Review Board in Stockholm, which determined that, owing to the population based nature of the study, informed consent from the study participants was not needed (Dnr 2011/1026-31/4; Dnr 02-556; Dnr 2012/1028/32; Dnr 2011/921-32).

  • Data sharing: Data from the study are available on request from corresponding author.

  • Transparency declaration: The lead author (PS) affirms that the manuscript is an honest, accurate, and transparent account of the study being reported; that no important aspects of the study have been omitted; and that any discrepancies from the study as planned (and, if relevant, registered) have been explained.

This is an Open Access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/.

View Full Text
Back to top