**2. Human papilloma virus**

HPV belongs to the family Papillomaviridae. Members of this family are small viruses of 45– 60 nm in diameter with icosahedral capsid. This family includes more than 189 genotypes,

which are distributed in 29 genera [1, 2]. The main features of human papillomavirus are listed in Table 1.


**Table 1.** Features Human Papillomavirus and *Chlamydia trachomatis*

The HPV genome consists of double-stranded DNA and is divided into three regions: the long control region (LCR), the early region (E), and the late region (L). Late proteins L1 and L2 code for capsid proteins [3, 4]. Region E is involved in the formation of non-structural proteins (E1– E7). E1 and E2 genes are involved in viral replication and transcription. E5, E6 and E7 genes encode proteins involved in oncogenesis related to HPV. E6 and E7 are involved in the viral transformation process, binding cellular proteins p53 and Rb, respectively, interfering with the cell cycle and inhibiting apoptosis [5].

The infection of HPV in both women and men may be asymptomatic or manifest itself in different forms: typical is the wart. However, atypical squamous intraepithelial lesions may culminate in the development of cancer. This has been studied particularly well for cervical cancer [5], leading to an increased investigation in this area. Because infection with this virus can be initially hard to detect it can allow progress to a chronic persistent infection or can cause changes in the infected cell disrupting the normal cell cycle. HPV is generally associated with cancer [6].

It has been established that genital tract infections have an effect on fertility, however, the effect of infection with HPV remains uncertain. It is recognized that HPV is one of the most common sexually transmitted infections in the world. There have been various studies that show a wide range in prevalence (from 1.4% to 44%) in the general population [7, 8]. Specifically it is reported to cause 16% infertility in men [9]. A review indicated that prevalence may be between 1.3% and 72.9% [10].

Moreover, male infertility is multi-factorial, including etiologic agents. The human papilloma virus has been identified as a possible cause of male infertility, but not all studies confirm the mechanisms by which this happens.

There have been controversial studies on the role of HPV on fertility. A study reported that in infertile couples only 7.8% were positive for DNA from HPV genotypes, however, in this study it was reported that it does not have an effect on semen quality [11]. Other studies show that HPV is reported in infertile couples.

which are distributed in 29 genera [1, 2]. The main features of human papillomavirus are listed

**Morphology** Icosahedral capsid Body elemental body and reticulum

**Type of biological agent** Virus Bacteria **Size** 45-60 nm 200-400 nm

**Genotypes** 189 genotypes 15 genotypes **Cellular position** Intracellular Intranuclear

Nonspecific lesions

Squamous intraepithelial lesions Cervical cancer and laryngeal

The HPV genome consists of double-stranded DNA and is divided into three regions: the long control region (LCR), the early region (E), and the late region (L). Late proteins L1 and L2 code for capsid proteins [3, 4]. Region E is involved in the formation of non-structural proteins (E1– E7). E1 and E2 genes are involved in viral replication and transcription. E5, E6 and E7 genes encode proteins involved in oncogenesis related to HPV. E6 and E7 are involved in the viral transformation process, binding cellular proteins p53 and Rb, respectively, interfering with

The infection of HPV in both women and men may be asymptomatic or manifest itself in different forms: typical is the wart. However, atypical squamous intraepithelial lesions may culminate in the development of cancer. This has been studied particularly well for cervical cancer [5], leading to an increased investigation in this area. Because infection with this virus can be initially hard to detect it can allow progress to a chronic persistent infection or can cause changes in the infected cell disrupting the normal cell cycle. HPV is generally associated with

It has been established that genital tract infections have an effect on fertility, however, the effect of infection with HPV remains uncertain. It is recognized that HPV is one of the most common sexually transmitted infections in the world. There have been various studies that show a wide range in prevalence (from 1.4% to 44%) in the general population [7, 8]. Specifically it is reported to cause 16% infertility in men [9]. A review indicated that prevalence may be between

Moreover, male infertility is multi-factorial, including etiologic agents. The human papilloma virus has been identified as a possible cause of male infertility, but not all studies confirm the

**Clinic manifestations** Sexually transmitted infection

**Table 1.** Features Human Papillomavirus and *Chlamydia trachomatis*

the cell cycle and inhibiting apoptosis [5].

Warts

Infertility

**Human Papillomavirus** *Chlamydia trachomatis*

Sexually transmitted infection

Pelvic inflammatory disease Lymphogranuloma venereum

Trachoma

Infertility

in Table 1.

70 Genital Infections and Infertility

cancer [6].

1.3% and 72.9% [10].

mechanisms by which this happens.

Different studies have linked infection with HPV in men with different clinical symptoms such as: genital warts, anal or penile intraepithelial lesions and different types of cancer in different regions – penis, anus, prostate and urethra [12, 13]. It has been found that human papilloma‐ virus could be infecting and persisting in different areas, such as the male accessory glands, penis, exfoliated cells, semen and sperm. Some research into these effects is referred to below.

In a study, it was reported that patients with accessory gland infection and HPV have been diagnosed with infertility. It was observed that there are significant changes in sperm quality. Particularly, there is a slight lower sperm motility, despite to have normal morphology, indicating that the co-infection could be an additional risk factor for infertility [14]. Moreover, infection has been observed in epithelial cells and exfoliated cells [15].

Studies in men showing persistent HPV (penis and semen samples) indicated higher levels in the penis (22.5 months) than in semen (15.3 months). This may demonstrate that men can transmit the disease to women despite being asymptomatic [16]. Different genotypes have been found in infertile men such as HPV-45, HPV-52, HPV-18, HPV-59 and HPV-16, which have been recognized as high-risk genotypes [11, 17]. It has been observed that HPV can infect both sperm and cell desquamation [18]. However, another study showed that sperm have low motility [19, 20].

Different techniques have been used in the diagnosis of HVP: *in situ* hybridization, dot blot, hybrid capture, real-time PCR, ELISA peptides, fused E6/E7 [21, 22, 23]; these methods have allowed a more accurate and timely diagnosis. The description of existing diagnostic methods is not discussed here, but it is important to mention that each has its own advantages and disadvantages – new technologies have become more accurate in diagnosis.

**Figure 1.** Pyramid showing the greatest location HPV in men, beginning with the penis at the top of the pyramid and the semen ending at the base of the pyramid.

Among the most studied area of HPV is the association with penile, larynx, head and neck cancers. It is estimated that HPV is the causative agent of 5% of human cancers [24].

In the review of Silva *et al.*, 2013 data show a prevalence in men, for different anatomical regions, in this order: penis, glans/corona, scrotum, perianal area, urethra and semen (Figure 1). This author also mentions that prevalence depends on the area, the technique used in detection and the geographical location of the patient [23].
