Molecular evidence of high-risk human papillomavirus infection in colorectal tumours from Cuban patients

Abstract

The association between colorectal cancer and human papillomavirus (HPV) infection is still unproven. The aim of this study was to investigate the presence of high-risk HPV (HR-HPV) DNA in colorectal tissues from Cuban patients. A total of 63 colorectal formalin-fixed paraffin-embedded tissues were studied (24 adenocarcinoma, 18 adenoma, and 21 colorectal tissues classified as benign colitis). DNA from colorectal samples was analysed by quantitative real-time polymerase chain reaction to detect the most clinically relevant high HR-HPV types (HPV-16, -18, -31, -33, -45, -52, and -58). Associations between histologic findings and other risk factors were also analysed. Overall, HPV DNA was detected in 23.8% (15/63) of the samples studied. Viral infections were detected in 41.7% of adenocarcinoma (10/24) and 27.7% of adenoma cases (5/18). HPV DNA was not found in any of the negative cases. An association between histological diagnosis of adenocarcinoma and HPV infection was observed (odd ratio = 4.85, 95% confidence interval = 1.40-16.80, p = 0.009). The only genotypes identified were HPV 16 and 33. Viral loads were higher in adenocarcinoma, and these cases were associated with HPV 16. This study provides molecular evidence of HR-HPV infection in colorectal adenocarcinoma tissues from Cuban patients.

Does human papillomavirus cause human colorectal cancer? Applying Bradford Hill criteria postulates

“…The positivity ratio of HPV detection in CRC samples was varied population wise from 0% [ 11 , 12 , 17 , 23 , 26 , 32 , 41 , 43 , 45 , 46 , 50 , 59 ] to 100% [ 13 , 54 ] in all the 59 studies, whereas the positivity ratio of HPV detection in normal and adjacent/benign samples was varied from 0% [ 21 , 22 , 29 , 30 , 43 , 49 ] to 84% (28) and 0% [ 17 , 22 , 26 , 41 , 42 , 45 , 46 , 50 , 52 , 57 ] to 69.56% [ 54 ], respectively.…”

“…Polymerase chain reaction (PCR) technique was employed by most of the studies [ 8 , 10 , 11 , 13 , 17 - 35 , 37 – 49 , 52 , 54 , 55 , 57 – 91 ] to detect the presence of HPV in the normal, adjacent/benign and diseased samples using L1, E6 and E7 gene-specific primers which specifically target [ 6 , 11 , 16 , 18 , 31 , 33 , 35 , 39 , 40 , 42 , 45 , 51 – 59 ] the subtypes of HPV, and from them, in addition, few studies also employed the second techniques including immunohistochemistry [ 67 ] and Southern blotting [ 13 , 28 ] to validate their PCR results.…”

“…The HPV positivity ratio reported in these studies was varied between 0% [ 11 , 12 , 17 , 23 , 26 , 32 , 41 , 43 , 45 , 46 , 50 , 59 ] and 100% [ 13 , 54 ]. In most of the case–control studies [ 12 , 17 – 27 , 29 – 32 , 35 – 57 ], the positivity ratio for HPV detection was higher in the cancerous samples as compared to the controls, whereas, in some studies [ 28 , 33 , 34 , 58 ], HPV positivity ratio was higher in the controls as compared to the CRC samples. Possible reasons for such population-specific inequalities in HPV detection could be non-modifiable factors such as genetic makeup and socially controllable factors such as health-seeking behaviour and differential access to the health facilities.…”

“…Up until now, only a single case–control study [ 57 ] relating HPV with CRC has been reported in Cuba. They analysed 42 CRC and 21 adjacent/benign controls using PCR with primers specifically targeting the E6 and E7 regions of the HPV genome and documented 35.7% HPV detection positivity ratio in CRC samples only ( Table 1 ).…”

“…Some of the studies that we summarised analysed only the CRC samples [ 8 , 11 , 13 , 59 , 64 , 65 , 67 , 71 , 74 , 75 , 79 , 80 , 84 ] and did not allow us to compare their results with normal or adjacent/benign controls. However, most of the studies also analysed the normal and adjacent/benign tissues along with CRC samples, and the comparison of their results demonstrated that HPV detection positivity ratios in CRC samples were higher in [ 12 , 17 , 27 , 29 – 32 , 35 – 57 ] studies, whereas lower in [ 28 , 33 , 34 , 58 ] studies as compared to the normal and adjacent/benign controls. However, none of the studies has reported the association of HPV with specific CRC subtype and histologic grade.…”