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

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  1 , A Athanasiou  2 , A A Veroniki  3 , G Salanti  4 , O Efthimiou  4 , N Raftis  5 , S Bowden  2 , M Paraskevaidi  6 , K Aro  7 , M Arbyn  8 , P Bennett  2 , P Nieminen  7 , E Paraskevaidis  5 , M Kyrgiou  9
Affiliations
Meta-Analysis

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 et al. Ann Oncol. 2020 Feb.

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.

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Figures

Figure 1
Figure 1
PRISMA flow chart.
Figure 2
Figure 2
Pooled incidence rate of cervical cancer per 100 000 woman-years. Subgroup analyses according to age at cervical intraepithelial neoplasia (CIN) treatment, treatment method for CIN, CIN grade, and length of follow-up. CI, confidence interval; IR, incidence rate; N/A, not available (i.e. meta-analysis not possible); PI, prediction interval.
Figure 3
Figure 3
Pooled relative incidence of cervical cancer as compared with the reference population. Subgroup analyses according to age at cervical intraepithelial neoplasia (CIN) treatment, treatment method for CIN, CIN grade and length of follow-up. CI, confidence interval; N/A, not available (i.e. meta-analysis not possible); PI, prediction interval; RR, relative risk. *Fixed effect estimate.
Figure 4
Figure 4
Pooled relative incidence of cervical and other cancers and mortality from cervical and vaginal cancer after treatment of cervical intraepithelial neoplasia (CIN) as compared with the reference population. CI, confidence interval; N/A, not available (i.e. meta-analysis not possible); PI, prediction interval; RR, relative risk.
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