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and 47.7% in oral squamous cell carcinomas. [124] Oral and chemotherapeutic drugs; there is limited success with
leukoplakia is associated with HPV6, HPV11 and HPV16 mostly side effects. [153] Therefore like all the other cancers,
and these may lead to malignant oral diseases. [125-127] early detection and vaccines can play a crucial role in RRP.
Similarly, HPV is detected more often with increased Although the present HPV vaccines protect against HPV
prevalence in oral lichen planus. [128] 11, there is the need for development of vaccines for other
HPV types, especially HPV6 for the prevention of RRP.
The overall prognosis of head and neck squamous cell
carcinomas seems to be better with HPV infected patients. BLADDER CANCER
Young individuals appear to have increased risk of having
HPV positive tonsillar and oropharyngeal carcinomas [129,130] The first association of HPV and bladder tumors was
with better prognosis and lower relapse risks compared reported in 1988. [154] The prevalence of HPV infection
to HPV negative head and neck squamous cell carcinoma in bladder carcinomas ranges from 0% to 81%. [155-159]
(HNSCC) patients. [131] Approximately 6% prevalence was Overall, the involvement of bladder cancer with HPV is
reported for HPV positive OSCCs. [132] However, more than controversial. Although some studies reported a positive
half of the patients with HNSCC (57%) were shown to have correlation between HPV infection through contribution
metastases to the brain where all are HPV positive. [133] of E6 and E7 oncogenic proteins, [160-163] some reported no
association between HPV infected bladder carcinoma. [164,165]
LUNG CANCER Furthermore, p16-INK4a was reported to be involved in the
development of bladder cancer through suppressing the
Lung cancer is one the foremost causes of cancer associated inactivation of Rb protein association with HPV infected
deaths worldwide. Although cigarette smoking plays a bladder carcinoma. [163,166,167] The controversy continues with
crucial role in lung cancer development, less than 20% of the inverted papiloma of the urinary tract and urothelial
the smokers have lung cancer. [134] Therefore, other factors carcinomas. In some reports HPV is associated with
including inactivation of tumour suppressor genes, such as inverted papilloma of the urinary bladder [168] and urothelial
p53, Rb and p16, and HPV infection have been proposed to carcinomas, [167,169] but in the others no association was
be involved in the development of lung carcinogenesis. [134,135] reported. [170,171]
The possible role of HPV in lung cancer was initially
proposed due to the similarities of the morphological HPVs, especially HPV16 and HPV18, were detected
epithelial changes detected in bronchial carcinomas with mostly in low grade (grade 1) tumours and never have
genital HPV lesions. [136,137] HPV detection in lung cancer they been reported for grade 3 carcinomas. [163,167,172-175]
was confirmed in 1988 [138] and the association of HPV with Therefore potentially HPV is only associated with low
lung cancer was then verified by detection of HPV DNA in grade carcinomas.
lung cancer samples. [139,140] However, the issue is debated
and controversial studies have been reported. [141,142] Some PENILE CARCINOMA AND ANAL
groups reported that E7 proteins of high risk HPV16 and CARCINOMA
HPV18 are detected, [143,144] some reported that none of
the HPV types are present in non-small lung cancer. [145] Penile carcinomas mainly originate in the squamous mucosa
An international pooled analysis of HPV association with of the glans, coronal sulcus or inner surface of the foreskin
lung cancers revealed that HPV DNA is present but in a of the penile. Penile cancers are rare and they usually occur
very small number of lung tumors. [146] Therefore, the direct in uncircumcised men. [176] About half (40-50%) of the
relevance of lung cancer with HPV requires further analysis. penile squamous cell carcinomas are related to the high risk
A recent meta-analysis data showed that HPV infection has HPV infection [52,177-180] and mostly the basaloid and warty
a strong relationship with lung cancer with significantly types of penile cancers are consistently related to HPV
increased risk of lung squamous cell carcinoma upon infection, whereas HPV DNA was only detected in some
HPV16 and HPV18 infection and in this meta-analysis, it of the keratinizing and verrucous penile carcinomas. [179]
is proposed that the HPV vaccination may lower the lung Mainly HPV16 (69%) and HPV18 (13%) play a role in the
cancer risk. [147] development of penile squamous cell carcinomas. High
[57]
risk HPV types, generally HPV16 and HPV18, are detected
Respiratory papillomatosis (RRP) is a serious condition in Bowenoid papulosis, which resemble genital warts but
that may spread to lungs and can progress to cancer. [148,149] with high grade squamous cell carcinoma in situ, can be
Patients with RRP have an increased risk of developing found on the external genitalia, perineum or perinally. [181]
laryngeal neoplasias and carcinomas. [150] RRP is mainly HPV16 and HPV18 are also associated with Eryhtroplasia
caused by the alpha-HPVs, HPV6 and/or HPV11. [151] The Queyrat, which is in situ carcinoma of the penile mucosa.
transmission of upper respiratory tract infections may be This carcinoma can also be present on the urethra, vulva,
passed on by sexual contact and from mother to child during tongue and oral mucosa. Buschke-Löwenstein tumors,
child birth canal. [4,152] Although many therapies have applied which cause destruction of the underlying tissues leading
for RRP patients, such as surgical, treatment with antivirals to transformation into squamous cell carcinoma and are

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