Potential Role of E4 Protein in Human Papillomavirus Screening: a Review

Document Type : Systematic Review and Meta-analysis


1 Department of Pathology, School of Medical Sciences, Universiti Sains Malaysia, Kubang Kerian, Kelantan, Malaysia

2 Histopathology Unit, Pathology Department, Hospital Sultanah Aminah, Johor Bahru, Malaysia


In 2006, cervical cancer was reported as the second most common cancer in women of Malaysia. This type of cancer has been shown to correlate with persistent high risk human papillomavirus (HPV) infection. Although HPV is well known to induce cervical cancer, knowledge of pathways that link the latent stage of the viral replication cycle to precancerous and cancerous stages remains incomplete. However, it is interesting to note that the virus can be isolated from tissues ranging from normal to low-grade squamous intraepithelial lesions as well as high-grade intraepithelial lesions (HSILs), thus prompting scientists to develop HPV detection methods for screening. Detection of HPV using viral proteins such as L1 and E1 is proposed to be very useful in assisting the management of high risk infection and cervical cancer. These tests however can lead to false positive results, largely due to the exisstence of asymptomatic or transient HPV infections within any given individual. Somes observation indicate that use of HPV proteins such as E6 and E7 might lead to false positive results. However, one particular HPV protein, E4 shows potential as an accurate marker of the tissue state following HPV infection. E4 expression has been shown to correlate with the levels of HPV DNA incorporation by the host. Thus, it is possible that E4 could serve as a useful marker to define stages of viral carcinogenesis.


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