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

I Kalliala; A Athanasiou; A A Veroniki; G Salanti; O Efthimiou; N Raftis; S Bowden; M Paraskevaidi; K Aro; M Arbyn; P Bennett; P Nieminen; E Paraskevaidis; M Kyrgiou

doi:10.1016/j.annonc.2019.11.004

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

Ann Oncol. 2020 Feb;31(2):213-227. doi: 10.1016/j.annonc.2019.11.004. Epub 2020 Jan 3.

Authors

I Kalliala¹, A Athanasiou², A A Veroniki³, G Salanti⁴, O Efthimiou⁴, N Raftis⁵, S Bowden², M Paraskevaidi⁶, K Aro⁷, M Arbyn⁸, P Bennett², P Nieminen⁷, E Paraskevaidis⁵, M Kyrgiou⁹

Affiliations

¹ Institute of Reproductive and Developmental Biology, Department of Surgery & Cancer, Faculty of Medicine, Imperial College London, London, UK; Department of Obstetrics and Gynaecology, University of Helsinki and Helsinki University Hospital, Helsinki, Finland.
² Institute of Reproductive and Developmental Biology, Department of Surgery & Cancer, Faculty of Medicine, Imperial College London, London, UK; Queen Charlotte's and Chelsea - Hammersmith Hospital, Imperial College Healthcare NHS Trust, London, UK.
³ Institute of Reproductive and Developmental Biology, Department of Surgery & Cancer, Faculty of Medicine, Imperial College London, London, UK; Department of Primary Education, School of Education, University of Ioannina, Ioannina, Greece.
⁴ Institute of Social and Preventive Medicine, University of Bern, Bern, Switzerland.
⁵ Department of Obstetrics and Gynaecology, University Hospital of Ioannina, Ioannina, Greece.
⁶ Institute of Reproductive and Developmental Biology, Department of Surgery & Cancer, Faculty of Medicine, Imperial College London, London, UK.
⁷ Department of Obstetrics and Gynaecology, University of Helsinki and Helsinki University Hospital, Helsinki, Finland.
⁸ Unit of Cancer Epidemiology, Scientific Institute of Public Health, Brussels, Belgium.
⁹ Institute of Reproductive and Developmental Biology, Department of Surgery & Cancer, Faculty of Medicine, Imperial College London, London, UK; Queen Charlotte's and Chelsea - Hammersmith Hospital, Imperial College Healthcare NHS Trust, London, UK. Electronic address: m.kyrgiou@imperial.ac.uk.

Abstract

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.

Keywords: CIN; HPV-related cancer; LLETZ; cancer incidence; cancer mortality; conisation.

Publication types

Meta-Analysis
Research Support, Non-U.S. Gov't
Systematic Review

MeSH terms

Alphapapillomavirus*
Female
Humans
Incidence
Middle Aged
Papillomavirus Infections* / complications
Papillomavirus Infections* / epidemiology
Uterine Cervical Dysplasia* / epidemiology
Uterine Cervical Dysplasia* / therapy
Uterine Cervical Neoplasms* / epidemiology
Uterine Cervical Neoplasms* / therapy

Abstract

Publication types

MeSH terms

Grants and funding