**1. Introduction**

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The Human Papillomavirus (HPV) has been shown to play a causative role in anal, head and neck, oral, oropharyngeal, penile, vaginal, vulvar and cervical cancers. The last one is the second most common cancer among women worldwide [1-3]. Some types of HPV have been established as the central cause of cervical carcinoma [4-7]

Acquisition of HPV is very common, particularly among sexually active young adults, and incidence of infection with oncogenic HPV types appears to be higher than the incidence of infection with non-oncogenic types [8]. Oncogenic HPV types 16 and 18 and history of other concurrent sexually transmitted diseases were found to be significantly associated with progression to cervical cancer [1-13].

More than 100 HPV types have been identified and about 40 types can infect the genital tract. Worldwide, HPV 16 is the most common high-risk type, present in 50%, followed by HPV 18, present in 14% of cervical cancers [9]. Same types of HPV were more frequent in malignant than in benign lesions, and infection with high-risk types of HPV is now considered the major risk factor for the development of cancer of the uterine cervix [1].

Thus, the HPV infection is necessary for the development of the cervical cancer. The develop‐ ment of this cancer is considered to be a multistep process, where HPV is necessary but in itself an insufficient cause. Disease can only develop when there is persistent HPV infection of the cervical epithelium [3,9].

Cervical cancer is considerate a rare complication of infection with high risk HPV (HR-HPV), but every abnormal or dysplastic lesion of the cervix is potentially malignant and may develop into cervical cancer over time. The incidence is highest in developing countries, largely as a

result of lack of screening programs and poor access to medical care [1]. The prevalence of HPV and the distribution of its types probably plays an important role as well. On the other hand, the relationship between others cancer types and HPV-associated is just emerging [10].

The process by which HPV facilitates tumour initiation and fosters tumour progression is an exceptional model to understand the development of many other human cancers and also allows identification of additional signalling pathways targeted in malignant progression [19]. The association between HPV and human cancer was first proposed more than three decades ago by Harald zur Hausen, and he was honored with one of two 2008 Nobel Prizes in Medicine for his isolation and characterization of HPV 16 in 1983 and later HPV 18 in cervical cancer [20]. The award recognized not only the importance of his discovery in the eventual documentation of the etiology of HPV in cervical and a number of other cancers, but also the importance of the application of his discovery to the clinical use of HPV testing and in implementation of the

Molecular Tools for Detection Human Papillomavirus

http://dx.doi.org/10.5772/55710

29

Additional, many studies have demonstrated the direct role of HPV infection in the develop‐ ment of several human cancers [12-15,21]. HPV 16 and HPV 18 are the most frequently found HPV types in cervical cancers worldwide, being detected in approximately 50 and 20% of the cases, respectively [2-22]. For this reason, the majority of the biological studies were focused

The viral genomes are replicated in synchrony with cellular DNA replication. After cell division, one daughter cell migrates away from the basal layer and undergoes differentiation. Differentiation of HPV-positive cells induces the productive phase of the viral life cycle, which requires cellular DNA synthesis machinery. The expression of E6 and E7 deregulates cell cycle control, pushing differentiating cells into S phase, allowing viral genome amplification in cells that normally would have exited the cell cycle. The late-phase L1 and L2 proteins encapsidate newly synthesized viral genomes and virions are shed from the uppermost layers of the

The induction of hyperproliferation by the E7 oncoprotein triggers apoptosis, which is blocked by the actions of the E6 oncoprotein. The cooperative actions of E6 and E7 efficiently immor‐ talize cells and this process is augmented by the actions of the E5 protein. The ability of E6 and E7 to target crucial regulators of proliferation, apoptosis, immortalization and genomic stability collectively promotes the emergence of a clonal population of cells with a growth advantage and an increased propensity for transformation and malignant progression [19].

The best-characterized HPV 16 E6 activity is its ability to induce degradation of the tumor suppressor protein p53 via the ubiquitin pathway. This cellular protein is a transcription factor that can trigger cell cycle arrest or apoptosis in response to a large variety of cellular stresses, such as hypoxia or DNA damages. Overall, the role of p53 is to ensure the integrity of the cellular genome, preventing cell division after DNA damage or delaying it until the damage has been repaired. The induction of p53 degradation appears to be an exclusive feature of E6

Codon 72 polymorphism on the 4th exon of TP53 is involved in multiple steps of carcinogenesis and may also account for genetic differences in susceptibility to cancer [24-26]. This most common polymorphism results in a non-conservative change at codon 72 of an arginine to a proline within a proline - rich region of p53 which is known to be important for the growth suppression and apoptotic functions [25]. It has been demonstrated that the TP53 polymor‐

HPV vaccine.

on these two HPV types.

epithelium [19].

proteins from the HR-HPV types [23].

The variability in HPV-attributable proportions for non cervical cancers, in part, arises from differences in HPV detection methods across studies as well as from true geographic differ‐ ences in HPV-attributable proportions [11]. Despite this variability, 90%–93% of anal cancers, 12%–63% of oropharyngeal cancers, 36%–46.9% of penile cancers, 40%–64% of vaginal cancers, and 40%–51% of vulvar cancers are potentially attributable to HPV infection [11-15].

Abnormal cervical epithelial cells can be detected microscopically following Papanicolaou (Pap) staining of conventional cervical smears or of the more homogeneous cell suspension from liquid cytology medium. This forms the basis of cervical screening programmes for detection of women at risk of disease progression, and also for incident infections [9,16]. Molecular detection of HPV provides a different approach to screening and patient manage‐ ment. In this chapter was described the diagnosis of HPV infection to screening cervical cancer and molecular tools to detect HPV-DNA/RNA.
