Detection of Human papillomavirus and the role of p16INK4a in colorectal carcinomas

Abstract

Introduction Human papillomavirus (HPV) infection is associated with the development of anogenital and head and neck cancers. In recent years a potential role of HPV in colorectal cancer (CRC) has been suggested. Objective To investigate the presence of HPV in colorectal carcinomas and to study the role of p16 INK4a as a marker of transcriptionally active HPV infection. In addition, to investigate the correlation between these findings and the CRC prognostic factors. Methods Case control study with 92 cases of colorectal cancers, 75 controls of normal tissue adjacent to the tumor, and 30 controls of precursor lesions, including polyps and colorectal adenomas. Paraffinized samples were used, HPV detection and genotyping were performed by PCR and reverse hybridization by using the INNO LIPA kit, with SPF10 plus primers. The expression of the p16 INK4a protein was investigated using immunohistochemistry. Data analysis was performed using descriptive, univariate statistics and survival curves were calculated by using the Kaplan Meier and log-rank method. Results HPV was detected in 13% of the cases and the most prevalent genotype was HPV 16. HPV DNA was not detected in either control groups. The high expression of p16 INK4a was observed in 30% of the cases, but it was not associated to the presence of HPV. The overall survival was 53.3% and was influenced by prognostic factors such as later stage, lymph node and distant metastasis.

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.…”

“…A couple of case–control studies [ 25 , 52 , 55 ] has been carried out in Brazil so far to analyse the association between HPV and CRC. They utilised PCR with primers specifically targeting the L1, E6 or E7 region of the viral genome and documented HPV detection positivity ratios with varying frequencies ranging from 13% [ 52 ] to 63.9% [ 25 ] in CRC samples, whereas 19.4% [ 25 ] in normal and 0% [ 52 ]–50% [ 25 ] in adjacent/benign controls. In the Brazilian population, HPV16 was the most commonly identified strain ( Table 1 ).…”

The first comprehensive genomic characterization of rectal squamous cell carcinoma

“…In different series (25), presence of TP53 mutation in aSCC is likely to be associated with HPV-negative tumors and confers poor prognosis as well as tumor relapse. It is licit to now consider HPV as a risk factor for rSCC like it is for aSCC and contrary to rADC [ 33 , 34 ]. This result gives an additional argument for treating rSCC like aSCC.…”

Human Papillomavirus Infection and Oropharyngeal and Gastrointestinal Cancers: A Causal Relationship?

“…HPV has been suggested as a potential risk factor for the development of CRCs. Many studies investigated the presence of HPV in colorectal cancer tissues and compared them to normal and surrounding tissues ( Table 4 ) [ 81 , 82 , 83 , 84 , 85 , 86 , 87 , 88 , 89 , 90 , 91 , 92 , 93 , 94 , 95 , 96 , 97 , 98 , 99 , 100 , 101 , 102 , 103 , 104 , 105 , 106 , 107 , 108 , 109 , 110 , 111 ]. In the majority of cases, the prevalence of HPV in cancer tissue has been higher than that in the control, suggesting a role for HPV in the oncogenesis of CRC.…”