Human Papilloma Virus infection and cervical cancer in Romania

Abstract

Infection with human papillomaviruses (HPV) is a major public health burden worldwide and is associated with a variety of epithelial lesions, including benign warts and several types of anogenital tumors, particularly cervical carcinoma.HPV can be grouped into cutaneous types and mucosal types based on their preferred tissue tropism. Cutaneous types are typically found in the general population and cause common warts. Mucosal HPV is further classified into high-risk and low-risk types, based on their association with cervical cancer. The most common low-risk types are HPV 6 and 11, detected most often in benign genital warts. HPV 16, 18, 31, and 45 are predominant types found in cervical squamous cell carcinoma. HPV 16 is the most prevalent type in cervical cancer (55%), followed by HPV 18 and HPV 45. Epidemiological evidence has convincingly demonstrated that infection with HPV is the greatest risk factor, its role in the progression of the precursor lesions to cervical cancer is well established. HPV is exclusively epitheliotropic, and their replication is linked to the differentiation process of the host cells. Normal squamous epithelial cells grow as stratified epithelium, with those in the basal layers dividing as stem cells of transient amplifying cells. After division, one of the daughter cells migrates upward and begins to undergo terminal differentiation while the other remains in the basal layer as a slow-cycling, self-renewing population. Productive papillomavirus infection begins when infectious virions gain access to cells of the basal layer, probably through micro-wounds. The viral genome is maintained in these cells at low copy number. These infected cells from the reservoir for the development of a productive wart. Early HPV genes E1 and E2 support viral DNA replication and its segregation such that the infected cells can be maintained in the lesion for a long period. As infected daughter cells migrate towards the epithelial surface, viral late gene products are produced to initiate the vegetative phase of the HPV life cycle, resulting in the high-level amplification of the viral genome. In the outer layers of the epithelium viral DNA is packaged into capsids and progeny virions are released to reinitiate infection. Given the worldwide burden of HPV infection (anogenital warts and neoplasia of several sites), prevention of infection could provide relief from an important public health threat. With the introduction of cervical screening in developed countries, the number of deaths from cervical cancer has declined dramatically, but in developing countries it still remains the number one of female cancer.