High risk human papillomavirus detection in semen

Human papillomaviruses (HPVs) are members of the Papillomaviridae family of DNA
viruses. More than 100 types have been identified, of which, about 60 types
infect the anogenital region. Anogenital HPV types have been further classified
into low-risk types (e.g., 6 and 11), which are associated with anogenital
warts and mild dysplasia, and high-risk types (e.g., 16, 18, 33 and 45), which
are associated with high-grade dysplasia and anogenital cancers, such as
cervical and anal carcinoma. Anogenital HPV infections are the most common
sexually transmitted infections (STI) with a lifetime risk of 80% in women and
most infections are asymptomatic or subclinical. The risk factors that aid the
establishment of this infection are multiple sexual partners, prolonged use of
oral contraceptives, high degree of parity, lack of circumcision, lack of
condom use, smoking, immunosuppresion, co infection with HIV and other sexually
transmitted agents. (Foresta et al., 2008c)
Most research has focused on HPV infection in women because of the correlation
between HPV infection and cervical cancer. High-risk types of HPV have been
detected in 99,7% of cervical carcinomas.(Walboomers et al., 1999) However, as
with any other STI, men are implicated in the epidemiological chain of the
infection. This suggests that there is a potential large number of men who
serve both as a carrier and vector of HPVs of which the oncogenic types have
been clearly established as the central cause of cervical cancer. Though, the
exact mechanism by which sexual contact promotes virus infection remains
unclear.
Besides its central role in cervical carcinogenesis, HPV has been recognized as
an important risk factor for several cancers in men, such as anal cancer and
penile carcinoma and its precursor lesions; flat penile lesions and penile
intraepithelial neoplasia (PIN). Several studies have provided estimates of HPV
prevalence among men; however these estimates widely range from
1.3%-72.9%.(Dunne et al., 2006) The prevalence of HPV varies on the basis of
sampling, processing and the anatomic site(s) or specimen(s) sampled. The sites
most likely to be HPV positive are the glans penis/coronal sulcus and the
penile shaft followed by the scrotum and the urethra.(Giuliano et al.,
2007;Smith et al., 2007;Nielson et al., 2007) In addition, HPV DNA and RNA have
also been found in the ductus deferens, epididymis and testis.(Svec et al.,
2003;Martorell et al., 2005)
Interestingly, a few studies have shown that HPV DNA is found in semen.(Chan et
al., 1994;Aynaud et al., 2002;Didelot-Rousseau et al., 2007) Green et al.(Green
et al., 1991) reported that semen HPV DNA are quite prevalent in males with and
without genital warts, although half as prevalent in males without genital
warts.. Lai et al.(Lai et al., 1996) confirmed the high rate of presence of HPV
DNA in sperm cells. However, it remains to be seen whether the HPV found in
semen is merely caused by shedding of infected cells from the urethra, or
represents an additional mode of HPV transmission, or both.
Possibly, human papillomaviruses bind to the sperm cell, and exploit the sperm
cell as vehicles for dispersal and mucus penetration within the female genital
tract. The exact localization of HPV in the different component of semen, i.e.
seminal plasma and sperm cells, has received little attention in literature. A
recent study using FISH has reported the finding of HPV DNA in the head of the
spermatozoa, but it was unclear whether it was integrated into the
nucleus.(Foresta et al., 2008a)
The rationale of this pilot study, is that when HPV or HPV genotypes,
specifically binds to sperm cells, this would have significant consequences for
the understanding of the mode of HPV transmission. Furthermore, this knowledge
could influence the results of IVF or ICSI procedures. Therefore, in this
study, we set out to investigate the prevalence and genotype distribution of
HPV DNA in semen, and its exact localization within the seminal fluid or on the
sperm cell. Furthermore, we aim to investigate the consistency of a diagnosed
HPV infection in semen, and a possible association with the presence of flat
penile lesions.
In case the results of this study show that HPV specifically binds to sperm
cells, subsequently, we will perform a larger study on the effects of HPV
infections in semen, on the results of IVF- and ICSI procedures.

Evaluate the prevalence, consistency, and genotype distribution of human
papillomavirus (HPV) in semen and to examine the exact localization of HPV
(i.e., in the seminal fluid and/or on the membrane or cytoplasm of the sperm
cell).

Evaluate the presence of flat penile lesions and the association with the
prevalence of infection with human papillomavirus (HPV) in semen.

Observational pilot study

Risks and burden are linked to the protocol procedures, such as a penile swab
and penoscopy. Although these procedures are carried out by medically qualified
personnel, they may cause some discomfort to the subjects. However, it is
expected that these procedures will generally be well-tolerated. Furthermore,
the subjects are asked to turn in 3 semen samples with time intervals of 1 week
for detection of hrHPV. The burden is that this will require 3 visits to the
outpatient clinic to hand in the samples. Finally, a questionnaire on sexual
behaviour is given to the subjects.
Participants will receive a financial compensation of 60 euro for taking part
in the study.