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Incidence and mortality from cervical cancer and other malignancies after treatment of cervical intraepithelial neoplasia: a systematic review and meta-analysis of the literature

Journal

ANNALS OF ONCOLOGY
Volume 31, Issue 2, Pages 213-227

Publisher

ELSEVIER
DOI: 10.1016/j.annonc.2019.11.004

Keywords

cancer incidence; cancer mortality; CIN; conisation; HPV-related cancer; LLETZ

Categories

Funding

  1. National Institute for Health Research (NIHR) under its Research for Patient Benefit (RfPB) Programme [PB-PG-0816-20004]
  2. Genesis Research Trust
  3. Sigrid Juselius Fellowship [P52483]
  4. Imperial Health Charity predoctoral fellowship [P73337]
  5. Wellcome Trust Imperial 4i/NIHR BRC clinical PhD fellowship [P77712]
  6. Eemil Aaltonen Foundation
  7. Finnish Gynaecological Society
  8. Jalmari and Rauha Ahokas Foundation
  9. Academy of Finland
  10. European Union's Horizon 2020 [754936]
  11. National Institutes of Health Research (NIHR) [PB-PG-0816-20004] Funding Source: National Institutes of Health Research (NIHR)

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Background: Although local treatments for cervical intraepithelial neoplasia (CIN) are highly effective, it has been reported that treated women remain at increased risk of cervical and other cancers. Our aim is to explore the risk of developing or dying from cervical cancer and other human papillomavirus (HPV)- and non-HPV-related malignancies after CIN treatment and infer its magnitude compared with the general population. Materials and methods: Design: Systematic review and meta-analysis. Eligibility criteria: Studies with registry-based follow-up reporting cancer incidence or mortality after CIN treatment. Data synthesis: Summary effects were estimated using random-effects models. Outcomes: Incidence rate of cervical cancer among women treated for CIN (per 100 000 woman-years). Relative risk (RR) of cervical cancer, other HPV-related anogenital tract cancer (vagina, vulva, anus), any cancer, and mortality, for women treated for CIN versus the general population. Results: Twenty-seven studies were eligible. The incidence rate for cervical cancer after CIN treatment was 39 per 100 000 woman-years (95% confidence interval 22-69). The RR of cervical cancer was elevated compared with the general population (3.30, 2.57-4.24; P < 0.001). The RR was higher for women more than 50 years old and remained elevated for at least 20 years after treatment. The RR of vaginal (10.84, 5.58-21.10; P < 0.001), vulvar (3.34, 2.39-4.67; P < 0.001), and anal cancer (5.11, 2.73-9.55; P < 0.001) was also higher. Mortality from cervical/vaginal cancer was elevated, but our estimate was more uncertain (RR 5.04, 0.69-36.94; P = 0.073). Conclusions: Women treated for CIN have a considerably higher risk to be later diagnosed with cervical and other HPV-related cancers compared with the general population. The higher risk of cervical cancer lasts for at least 20 years after treatment and is higher for women more than 50 years of age. Prolonged follow-up beyond the last screening round may be warranted for previously treated women.

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