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located on the penile glans, prepuce, vulva, vagina and Genital warts can be found on penile shaft, base of the
perianal sites, are also associated with low risk HPVs, HPV6 penis, scrotum, pubic region, glans and rectal area. In
and HPV 11. [182,183] Additionally, in both males and females, women, they are mostly present in the labia minora and
approximately 85-95% of the anal cancers are HPV DNA vaginal opening. [197] In the decision of the therapy strategy,
positive. [52,104] Of these, HPV16 (75%) and HPV18 (3%) are many factors, such as morphology of the lesion, HPV
the causes for almost all the cases of anal cancers. [56,184] classification and immune competent status, are taken into
account. Unfortunately, none of the treatment strategies,
SKIN CANCER including targeted lesion destruction or immunologic
modification, are shown to clear the HPV infection or avoid
Similar to the head and neck, bladder and breast cancers, the the recurrence. With the use of HPV vaccines, the incidence
involvement of HPV in cutaneous squamous cell carcinoma of the warts has been decreased. [198] If these warts remain
has not been surely established. A range of nonmelanoma untreated, they can either regresses spontaneously or they
skin cancer forms contain DNA from beta HPV types. [185] can grow larger and become more numerous resulting in
HPV induced skin cancers include cutaneous squamous cell complicated cases. [192] Therefore, prevention HPV infection
carcinoma and superficial squamous cell carcinoma, such and therefore formation of these warts will be the optimum
as Bowen’s disease. [186] Approximately 30% individuals goal.
with infection develop invasive squamous cell carcinomas
with 90% of these tumors correlated with HPV5 and CONCLUSION
HPV8. [36,187] Genetic susceptibility to HPV is demonstrated
with epidermodysplasia verruciformis; however, HPV In the recent years, the biology of HPV infection and its role
infection alone is not enough to develop cancerogenesis in the progress of cancer have been widely evaluated. All
in epidermodysplasia verruciformis. Mainly, these the data discussed in this review point out the significance
[42]
tumors are induced by sun explosion and ultraviolet of HPV infection in several benign and malignant diseases.
radiation. Cells with HPV5 and HPV8 E6 proteins Although the understanding of association of HPVs with
disturb DNA double strand break repair [188] and reduces cervical cancer is very well established further studies are
the efficiency of base excision repair pathway [189] causing required to analyse the relationships between HPV and
higher sensitivity to UV-B exposure. It may be possible certain cancers including breast, lung, bladder, some types
that because of impaired DNA repair activity, patients of head and neck cancers and penile cancers.
with acquired immunodeficiency syndrome or patients
with epidermodysplasia verruciformis are more subjected To improve the mortality and morbidity of HPV associated
for the infections and at a higher risk of developing HPV cancers and diseases, there is an enormous need for early
associated cutaneous malignancies. [185,190,191] In order detection and prevention strategies. Although screening
to reduce the prevalence of HPV induced skin cancers, programs for early detection strategies have been developed
diagnosis of skin manifestations caused by HPV should be for some cancers, such as cervical, there is still a big gap to
routinely checked. [186] be filled for other precancerous lesions, such as for some
of the head and neck carcinomas. One of the examples of
ROLE OF HPV IN NON-CANCEROUS these screening strategies may involve oral examination,
DISEASES cytology and salivary HPV DNA tests which may provide a
better early diagnosis for oral and oro-pharyngeal cancers.
One of the most common non-oncogenic HPV diseases Moreover development and spread of more cost-effective
involves genital warts and the clinical manifestations vaccines is mandatory. Availability of low cost screening
extend from flat and common warts and cauliflower like or may prevent the future generations to develop HPVs
filiform warts. [186] The genital warts are mostly common in induced cancers. In light of this knowledge, HPV vaccines
younger people with the age of less than 25 years old and are useful in the protection against cervical, oral and oro-
the transmission is more than 60% with an incubation time pharyngeal cancers. However, it should be kept in mind that
between 2 to 8 months. [192] Various clinical presentations are the current HPV vaccines do not protect against all HPV
observed when keratinocytes respond to the HPV infection types, particularly beta-HPV types and their associated
depending on the HPV type and the anatomical site. Genital diseases. Therefore, despite all these advances, other
warts are mainly associated with HPV6 and HPV11. strategies for early detection and prevention for different
Although mainly low risk HPV types, HPV6 (89%) and HPV types are required.
HPV11 (11%), [193] both high and low risk HPV types may
cause genital warts. [194] Bowenoid papulosis is described by Financial support and sponsorship
several flat patches in genital area. Similarly, condylomata Near East University, Center of Excellence research fund
plana are flat warts that have been associated with HPV (www.neu.edu.tr).
infection. [195] Recurrence of genital warts with progression
of lesions even after 3 months are reported in one-third of Conflicts of interest
individuals with presence of genital warts. [196] There are no conflicts of interest.

Journal of Cancer Metastasis and Treatment ¦ Volume 2 ¦ June 15, 2016 ¦ 207