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are often detected in cervical cancers as well as other although HPV may play a role in vulvar cancer, this
epithelial tumors. association is not clear.

The underlying mechanism of the progression from CIN1 BREAST CANCER
through CIN2, CIN3 and eventually cancer is not well
established, it may be due to the early integration events Several epidemiological studies reported HPV detection in
in CIN1 or due to deregulation of viral gene expression. breast cancer samples. [105-109] Nevertheless the role of HPV
It is also possible that the initial deregulation leads to in breast carcinogenesis is by far not certain and further
instability of chromosomes and causes integration. It is randomized control trials are required to establish the
believed that the integration arises in high grade lesions, definite role of HPV in breast cancer development.
such as CIN2 and CIN3 and the deregulation of E6 and E7
expression may increase or remain at a constitute level. [92,93] HEAD AND NECK CARCINOMAS
In this scheme, flat warts can be resembled in CIN1 lesions,
however the proliferation level of the cell is lower in the Head and neck carcinomas involve a wide range of tumors
[110]
basal and parabasal layers. Increased expression levels and is one of the most common cancers worldwide. The
[13]
of E6 and E7 in high-risk HPV type infections causes prevalence of HPV DNA in head and neck cancers depends
[104]
CIN2+ phenotypes. This phenotype leads genetic changes on the cancer site, geography and ethnicity. The most
that contribute to cancer progression. These suggest that consistent prevalence of HPV infection is the oropharyngeal
cancers with an association of 35-50% in developed
low expression levels of E6 and E7 does not affect the
function of the cellular targets in CIN1 and therefore does cancers, whereas the HPV is detected in approximately
[52,84]
not contribute to cancer progression. In CIN2/ CIN3+, the 5-15% within the rest of the oral cavity. The overall
viral deregulation assists the viral episome into the host cell risk factors for head and neck carcinomas include tobacco
chromosome. This may further cause deregulation of E6 smoking and alcohol consumption.
and E7 expression. In clinical vaccine trials it was shown The first cases of HPV relationships with oral cell squamous
that young women can have CIN2+ soon after infection [94-97] cell carcinomas were reported in 2008 for lingual cancer,
for these cases, it is possible that deregulation of the gene tonsil cancer and oropharyngeal cancers. [111,112] Overall the
expression is due to cell signaling changes or epigenetic prevalence of these cancers are higher in men compared to
[98]
modifications, such as viral DNA methylation. [99] women. [113] Oropharyngeal carcinomas (OPCs) are the most
studied and the most characterised type of head and neck
An important step has been taken towards prevention of carcinomas. In the last decade the incidence of HPV related
HPV induced cervical cancers with the use of vaccines OPCs have doubled in number of patients and therefore
against HPV. However, due to various reasons, including the more attention has drawn to these cancer types. [114] HPV
unavailability of the vaccines in certain regions of the world positive oropharyngeal cancers are mainly associated
or the high costs of the vaccines, the wide application of with oral sex and rare p53 mutation. [115] Interestingly HPV
the vaccines is not available. Therefore, in case of cervical infection was shown to improve the prognosis of OPC with
cancer development, early detection strategies and treatment better survival is reported in HPV positive OPCs [116] and
play a vital role to prevent any deaths. The treatment for the therefore these patients may have a chance to benefit from
early cervical cancers is usually performed by conisation a less intense treatment strategy. [117] Chemotherapy using
or radical hysterectomy. For the more advanced tumors, paclitaxel, cisplatin on centuximab; followed by concurrent
cisplatin based chemo-radiotherapy is preferred that results radiation has been used in treatment of OPC patiens. [118] With
in 65-80% survival rates. Surgical excisions are usually the increasing number of HPV associated OPC patients, the
the standard for the HPV associated anogenital lesions. [100] use of antiviral and immunotherapeutic strategies show an
The treatment strategy for CIN is to eliminate the abnormal improved outcome. Although HPV related OPC have
[42]
HPV infected precancerous cells and maintain the cervical increased through the years, the HPV negative OPCs still
integrity. One of the most commonly used treatments for account for the majority of the OPC patients.
CIN involves loop electrosurgical excision procedure,
electrofulgaration and cryotherapy. [101] The HPVs, mostly HPV16 and HPV33, were detected
in quarter of the patients with invasive laryngeal cancers
The other lower genital cancers include vulvar and vaginal and are predominantly detected in women compared to
cancers. Majority of the vulvar and vaginal cancers are men. [119-121] HPV is also associated with potential malignant
squamous cell carcinomas. In majority of the cancers of disorders, such as erythroplakia, oral leukoplakia and
[57]
the vagina HPV DNA is detected; approximately half of the oral lichen planus. [122] Erythroplakia has the highest
vaginal cancers are caused by HPV16 (54%) followed by risk of malignant transformation. Half of the cases with
HPV18 (8%). Similarly, HPV DNA is detected in most erythroplakias alone is associated with HPV infection [123]
[57]
of the vulvar intraepithelial neoplasia, however only half of and the frequency of the HPV detection influences the
these neoplasias causes cancer. HPV16 is associated with severity of the lesions. In one study the HPV prevalence
32% and HPV18 with 4% of the cases. [57,102-104] Therefore, was 32.8% in oral lichen planus, 40.9% in oral leukoplakia

Journal of Cancer Metastasis and Treatment ¦ Volume 2 ¦ June 15, 2016 ¦ 205