**3. Prevalence and incidence**

The American Cancer Society has estimated that more than 6 million people are infected by HPV each year, with 3 million affecting the 15- 25 age group [14].

Asymptomatic oral and oropharynx HPV prevalence at oral cavity has not yet been established [15], probably because different methods were used in different studies [3]. Methods have varied in terms of size of samples, collecting procedures, test sensibility and use of PCR or PCR inhibitors. This may explain the huge variation in HPV detection rate: 22 to 60% or 0 to 81.1%, depending on the methods and on the studied population [15].

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

#### **3.1. Oral human papillomavirus infection**

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

HPV genome presents a notable organization. It weighs 5.2x106

**2.1. Genome structure**

18 Trends in Infectious Diseases

among the potentially high-risk types [12].

**3. Prevalence and incidence**

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].

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].

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

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

The American Cancer Society has estimated that more than 6 million people are infected by

Asymptomatic oral and oropharynx HPV prevalence at oral cavity has not yet been established [15], probably because different methods were used in different studies [3]. Methods have varied in terms of size of samples, collecting procedures, test sensibility and use of PCR or PCR

malignant, they can concurrently present with the high-risk malignant injury [9].

HPV each year, with 3 million affecting the 15- 25 age group [14].

D and contains 7.200 – 8.000

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

#### **3.2. Sexual and nonsexual transmission**

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 virus infection [6, 18, 19].

Oral HPV can be transmitted by direct skin-skin contact [3] and self-inoculation [1, 4]. Upper airway transmission has not yet been established [8].

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

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