**2. The biology of human papillomavirus — Virion structure**

HPV is a small DNA virus belonging to *Papillomaviridae* family [1, 2, 7, 8]. Its virion consists of a non enveloped, singular double stranded DNA molecule [5, 8, 9], of about 7.9kb [8], involved by a capsid, of about 55 nm in diameter [8, 9], containing only two structural proteins [8].

inhibitors. This may explain the huge variation in HPV detection rate: 22 to 60% or 0 to 81.1%,

Oral HPV Related Diseases: A Review and an Update 19

Recent meta-analysis has demonstrated that HPV is an isolated risk factor for the development of oral carcinoma [2]. Oral squamous cell carcinoma is known to be linked with both heavy

When oral mucosa is considered normal, the epithelium may serve as a container of HPV which would be activated at some point in time and induce injury [16]. A huge number of different oral diseases may be associated with oral HPV, but they rarely cause lesions [17]. Lesions may

Many studies have discussed HPV transmission, but the mechanisms involved remain unknown. Unprotected sexual intercourse is its leading cause, particularly oral-genital sex, when the genital mucosa is infected by the virus, which will be present both clinically and subclinically [1, 16] in adolescent and adults. Early sexual relationships, high number of sexual partners, parity, smoking and another sexually transmitted infection may elevate the rate of

Oral HPV can be transmitted by direct skin-skin contact [3] and self-inoculation [1, 4]. Upper

Infant HPV is mainly transmitted at birth by infection of the maternal cervix. Thus, the recurrent laryngeal papillomatosis seems to be acquired by such manner [19, 20]. However, another transmission route is mother-fetus, before, during or after the child-birth [1, 4, 8] that

In the social sphere, people who have yet to initiate sex life have a low probability of HPV infection. On the other hand, people who started their sex life earlier or have a promiscuous sexual life are more likely to have sexually transmitted infections, including HPV. In the economical sphere, it has been found that low levels of HPV infection were strongly related

Early age initial sexual activity, oral sex, more than one sexual partner, not wearing condoms, infrequent use of condoms all pose important risks to any sexually transmitted infection, such as HPV. Homosexuals tend to have greater number of sexual partners than heterosexuals, and as such, they should be more commonly infected than heterosexuals, but studies have yet to

may be made possible by infected amniotic fluid and umbilical cord blood [21].

range from benign warts, which are far more common, to malignant injuries [6].

depending on the methods and on the studied population [15].

drinking and smoking and it has been related to HPV [6, 7].

**3.1. Oral human papillomavirus infection**

**3.2. Sexual and nonsexual transmission**

airway transmission has not yet been established [8].

The transmission of HPV through fomites may also occur [22].

virus infection [6, 18, 19].

**4. Risk and protective factors**

with higher income levels [4].

confirm this trend [4, 8].

HPV genome presents a notable organization. It weighs 5.2x106 D and contains 7.200 – 8.000 pairs of nitrogenous bases (pnb) [9]. All putative open reading frames (ORFs) are limited to only one strand of DNA [8]. Non-coding strand probably forms a second, which bears pieces of preserved ORFs, irrespective of localization and composition [8], Chlaudhary et al (2009) have suggested that the basis of the HPV molecule DNA can be divided in three parts. The first part, with 4.000 pnb, accounts for viral replication and cell transformation while the second part, with 3.000 pnb, represents an important codification zone, since it encodes the viral particle structural proteins. The last one, with only 1.000 pnb, contains a non-coding zone; it is, however, fundamental, since the viral origin of replication belongs to this part [9].

#### **2.1. Genome structure**

The difference of HPV types is due to the variation of E6 and E7 sequence of nitrogenous bases. This variation can produce either an easier to inhibit gene or a harder to inhibit one, thus stratifying the virus oncogenic phenotype into high, intermediate and low risk types [7].Besides its oncogenic potential, the HPV types vary according to tissue tropism and their association with these tissues [10]. Over a 100 HPV types [7] have been identified, but only 25 (HPV - 1, 2, 3, 4, 6, 7, 10, 11, 13, 16, 18, 31, 32, 33, 35, 40, 45, 52, 55, 57, 58, 59, 69, 72, 73) were associated with benign or malignant lesions [3, 10]. Low-risk HPV (6, 11, 38, 40, 42, 54, 55, 61, 62, 64, 67, 69, 70, 71, 72, 81, 83, 84, 89) [11] causes injuries which produce abnormal cell growth [8]; however, they are unlikely to undergo malignant neoplastic transformation. High-risk HPV (16, 18, 26, 31, 33, 35, 39, 45, 51, 52, 53, 56, 58, 59, 66, 68, 73, 82) [11] are likely to induce malignant neoplastic transformation [3, 11]. Recently HPV- 26, 53, 66 have been found to be among the potentially high-risk types [12].

HPV - 6, 11 are related to condyloma *acuminatum* and, in children, laryngeal papilloma, conjuntival papilloma and genital warts [13]. HPV – 16, 18, mainly, but also 31, 32 and 35 are associated with squamous cell carcinoma [11]. Although benign forms rarely developed into malignant, they can concurrently present with the high-risk malignant injury [9].
