Smoking as a major risk factor for cervical cancer and pre-cancer: Results from the EPIC cohort

Research output: Contribution to journalArticle


A total of 308,036 women were selected from the European Prospective Investigation into Cancer and Nutrition (EPIC) study to evaluate the association between tobacco smoking and the risk of cervical intraepithelial neoplasia of grade 3 (CIN3)/carcinoma in situ (CIS) and invasive cervical cancer (ICC). At baseline, participants completed a questionnaire and provided blood samples. During a mean follow-up time of 9 years, 261 ICC cases and 804 CIN3/CIS cases were reported. In a nested case-control study, the baseline sera from 609 cases and 1,218 matched controls were tested for L1 antibodies against HPV types 11, 16, 18, 31, 33, 35, 45, 52, 58, and antibodies against Chlamydia trachomatis (CT), and Human Herpes Virus 2 (HHV-2). Cervical samples were not available for HPV-DNA analysis in this study. Multivariate analyses were used to estimate associations between smoking and risk of CIN3/CIS and ICC in the cohort and the case-control studies. In the cohort analyses smoking status, duration and intensity showed a two-fold increased risk of CIN3/CIS and ICC, while time since quitting was associated with a two-fold reduced risk. In the nested case-control study, consistent associations were observed after adjustment for HPV, CT and HHV-2 serostatus, in both HPV seronegative and seropositive women. Results from this large prospective study confirm the role of tobacco smoking as an important risk factor for both CIN3/CIS and ICC, even after taking into account HPV exposure as determined by HPV serology. The strong beneficial effect of quitting smoking is an important finding that will further support public health policies for smoking cessation. What's new? Tobacco smoking is a cited cause of cervical cancer, but whether it causes cervical malignancy independent of human papillomavirus (HPV) infection is unclear. Here, strong associations were found between most measures of tobacco smoking and the risk of cervical intraepithelial neoplasia of grade 3/carcinoma in situ and invasive cervical cancer, after taking into account past exposure to HPV infection. Quitting smoking was associated with a 2-fold risk reduction. The findings confirm the role of tobacco smoking in cervical carcinogenesis and show that quitting the habit has important benefits for cancer protection.


  • Esther Roura
  • Xavier Castellsague
  • Michael Pawlita
  • Noemie Travier
  • Tim Waterboer
  • Nuria Margall
  • F. Xavier Bosch
  • Silvia de Sanjose
  • Joakim Dillner
  • Inger T. Gram
  • Anne Tjonneland
  • Christian Munk
  • Valeria Pala
  • Domenico Palli
  • Kay-Tee Khaw
  • Ruanne V. Barnabas
  • Kim Overvad
  • Francoise Clavel-Chapelon
  • Marie-Christine Boutron-Ruault
  • Guy Fagherazzi
  • And 27 others
  • Rudolf Kaaks
  • Annekatrin Lukanova
  • Annika Steffen
  • Antonia Trichopoulou
  • Dimitrios Trichopoulos
  • Eleni Klinaki
  • Rosario Tumino
  • Carlotta Sacerdote
  • Salvatore Panico
  • H. B(as) Bueno-de-Mesquita
  • Petra H. Peeters
  • Eiliv Lund
  • Elisabete Weiderpass
  • M. Luisa Redondo
  • Maria-Jose Sanchez
  • Maria-Jose Tormo
  • Aurelio Barricarte
  • Nerea Larranaga
  • Johanna Ekström
  • Maria Hortlund
  • David Lindquist
  • Nick Wareham
  • Ruth C. Travis
  • Sabina Rinaldi
  • Massimo Tommasino
  • Silvia Franceschi
  • Elio Riboli
Research areas and keywords

Subject classification (UKÄ) – MANDATORY

  • Cancer and Oncology


  • cohort study, cervical cancer, smoking, Human Papillomavirus serology, EPIC
Original languageEnglish
Pages (from-to)453-466
JournalInternational Journal of Cancer
Issue number2
Publication statusPublished - 2014
Publication categoryResearch