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Meta-Analysis
. 2019 Jan;120(2):256-268.
doi: 10.1038/s41416-018-0273-9. Epub 2018 Nov 28.

Increased risk of second cancers at sites associated with HPV after a prior HPV-associated malignancy, a systematic review and meta-analysis

Duncan C Gilbert  1   2 , Katie Wakeham  3 , Ruth E Langley  4 , Claire L Vale  4
Affiliations
Meta-Analysis

Increased risk of second cancers at sites associated with HPV after a prior HPV-associated malignancy, a systematic review and meta-analysis

Duncan C Gilbert et al. Br J Cancer. 2019 Jan.

Abstract

Background: High-risk human papilloma viruses (HPV) are a causative agent of anogenital and oropharyngeal cancers. Patients treated for a preinvasive or invasive HPV-associated cancer may be at increased risk of a second such malignancy.

Methods: We performed a systematic review and random effects meta-analysis to estimate the risk of HPV-associated cancer after prior diagnosis. Studies reporting second cancers at anogenital and oropharyngeal sites after prior diagnoses (preinvasive/invasive HPV-associated cancer) were identified. Studies reporting standardised incidence ratios (SIRs) were included in formal meta-analyses of second cancer risk. (PROSPERO ID: CRD42016046974).

Results: Searches returned 5599 titles, including 60 unique, eligible studies. Thirty-two (98 comparisons) presented SIRs for second cervical, anal, vulvo-vaginal, penile, and/or oropharyngeal cancers, included in the meta-analyses. All studies (and 95/98 comparisons) reported increased cancers in the population with previous HPV-associated cancer when compared to controls. Pooled SIRs for second primary cancers ranged from 1.75 (95% CI 0.66-4.67) for cervical cancer after primary anal cancer, to 13.69 (95% CI 8.56-21.89) for anal cancer after primary vulvo-vaginal cancer.

Conclusions: We have quantified the increased risk of second HPV-associated cancer following diagnosis and treatment for initial cancer or preinvasive disease. This has important implications for follow-up, screening, and future therapeutic trials.

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Conflict of interest statement

The authors declare no competing interests.

Figures

Fig. 1
Fig. 1
PRISMA flow diagram of identification and selection of eligible studies. *Included in discussion with respect to estimation of absolute risk of subsequent HPV-associated cancer, Table S1. #Included in Table S2
Fig. 2
Fig. 2
Standardised incidence ratios of second primary cancer after HPV-associated primary tumours at the same location
Fig. 3
Fig. 3
a Standardised incidence ratios of anal cancer after HPV-associated primary tumours. b Standardised incidence ratios of cervical cancer after HPV-associated primary tumours. c Standardised incidence ratios of vulvo-vaginal cancer after HPV-associated primary tumours. d Standardised incidence ratios of oropharyngeal cancer after HPV-associated primary tumours
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