Review
The prevalence of human papillomavirus in colorectal adenomas and adenocarcinomas: A systematic review and meta-analysis

https://doi.org/10.1016/j.ejca.2014.01.019Get rights and content

Abstract

Background

The role of human papillomavirus (HPV) in colorectal cancer has been widely studied with conflicting results. We performed a systematic review and a meta-analysis to estimate the prevalence of HPV in colorectal adenocarcinomas and adenomas, and test the potential association.

Methods

The pooled HPV prevalence was estimated using a random effects model and the I2 statistic was used to describe the amount of heterogeneity. Potential sources of heterogeneity were evaluated by meta-regression and stratified analyses. For the studies on adenocarcinomas including control tissue, random effects estimates of odds ratios (ORs) and 95% confidence intervals (CIs) were calculated.

Results

Thirty-seven studies were included. Among the 2630 adenocarcinomas, the pooled HPV prevalence was 11.2% (95% CI, 4.9–19.6%) with substantial between-study heterogeneity (I2 = 97.2%). The HPV prevalence varied by geographical region with highest prevalence in South America (45.1%, 95% CI, 21.9–69.4%), Asia (39.2%, 95% CI, 20.3–60.0%) and the Middle East (32.2%, 95% CI, 1.1–79.3%), and by detection method with the highest HPV prevalence in PCR-based studies. In the eight case–control studies, the pooled HPV prevalence was 36.8% (95% CI, 21.3–53.8%) in adenocarcinomas and 1.6% (95% CI, 0.0–9.6%) in controls giving an OR of 6.0 (95% CI, 2.0–17.9%) for the association between HPV and colorectal cancer. Among the 415 adenomas, the pooled HPV prevalence was 5.1% (95% CI, 0.0–17.8%; I2 = 93.7%).

Conclusions

HPV may be associated with a subset of colorectal cancers. Future large-scale multicenter case–control studies with data on risk factors such as lifestyle and sexual behaviour are needed.

Introduction

Colorectal cancer is the fourth most common cancer worldwide with an estimated 1,360,602 new cases and 693,881 deaths annually [1]. Approximately 95% of colorectal cancers are adenocarcinomas [2], and the main precursor lesions are the adenomas [2].

The progression of adenomas to adenocarcinomas is influenced by genetic and environmental factors [3]. One environmental factor which may be associated with colorectal cancer is human papillomavirus (HPV) [4], [5], [6]. HPV is a necessary cause of cervical cancer [7] and is also associated with a subset of other anogenital cancers (e.g. vulvar, vaginal, anal and penile cancer) and head and neck cancers [8]. However, the association between HPV and colorectal cancer remains inconclusive.

HPV could potentially infect the colorectum by an ascending infection from anogenital sites [9], [10], or through haematogen or lymphogen spread [11], [12], [13]. Since the first reports in the late 1980s [14], [15], [16], [17], an accumulating amount of studies have investigated the prevalence of HPV in colorectal cancer with prevalence estimates ranging from 0% [14], [16], [17], [18], [19], [20], [21], [22], [23], [24], [25], [26], [27], [28], [29], [30] to 84% [31]. Although two previous reviews [4], [5] and one meta-analysis [6] on the association between HPV and colorectal cancer have been published, they had weaknesses such as non-exhaustive literature search; inclusion of conference abstracts without peer-review; limited statistical analysis; or inclusion of studies with potential overlapping study populations or immunosuppressed patients [4], [5], [6]. Furthermore, new data on the HPV prevalence in colorectal cancer have been published recently [11], [30], [32], [33] including one large study with 555 cases [33]. These studies were not included in the previous reviews and meta-analyses.

We systematically searched the literature and performed an updated review and meta-analysis of all studies of the HPV DNA prevalence in colorectal adenocarcinomas and adenomas. Meta-regression and stratified analyses were applied to investigate variables potentially related to the HPV prevalence and finally, we tested the association between HPV infection and colorectal adenocarcinomas by pooling studies with colorectal control tissue.

Section snippets

Search strategy

We searched PubMed and Embase up to 22 March, 2013 for all studies of the HPV DNA prevalence in colorectal adenocarcinomas and adenomas. Combinations of search terms for HPV and carcinoma, adenoma, or polyps of the colon or rectum were used (Supplementary, Table 1). We identified 1267 records in PubMed and 1785 records in Embase (Fig. 1). After removal of duplicates (n = 882), all abstracts (n = 2170) were reviewed independently by two authors (LB and LTT). Full-text copies of potentially relevant

Results

In total, 40 studies met our eligibility criteria. Among these, three studies were excluded due to overlapping study populations [42], [43], [44]. Among the remaining 37 studies, 34 contained information on colorectal adenocarcinomas [9], [10], [11], [14], [15], [16], [17], [18], [19], [20], [21], [22], [23], [24], [25], [26], [27], [28], [29], [30], [31], [32], [33], [45], [46], [47], [48], [49], [50], [51], [52], [53], [54], [55] and eight contained information on adenomas [16], [19], [30],

Discussion

In this meta-analysis, we estimated a pooled HPV prevalence of 11.2% in 2630 colorectal adenocarcinomas and 5.1% in 415 adenomas. However, one of the main observations was the wide variation in reported HPV prevalence among studies, ranging from 0% to 84% in the cancers. We also found wide variation in reported type-specific HPV prevalence. The overall prevalence of HPV in colorectal adenocarcinomas was highest in studies from South America, Asia and the Middle East, ranging from 32% to 45%,

Conflict of interest statement

LTT received travel grant from Sanofi Pasteur MSD. SKK received lecture fees, scientific advisory board fees and unrestricted institutional research grants from Merck and Sanofi Pasteur MSD, and scientific advisory board fees from Roche.

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