MOUTH CANCER AND THE HUMAN PAPILLOMA VIRUS


The human papilloma virus (HPV) is one of the most common virus groups in the world to affect the skin and mucosal areas of the body. Over eighty types of HPV have been identified. Different types of the human papillomavirus are known to infect different parts of the body. It infects the epithelial cells of skin and mucosa. The epithelial surfaces include all areas covered by skin and/or mucosa such as the mouth, throat, tongue, tonsils, vagina, penis, and anus. Infection with the virus occurs when these areas come into contact with a virus, allowing it to transfer between epithelial cells.

Warts
The most common forms of the virus produce warts (papilloma's) on the hands, arms, legs, and other areas of the skin. The wart-like growths are called condyloma tissues. Condyloma tissue appears like a small, cauliflower-type growth on the skin. These growths are usually painless, but can cause some irritation, itching, or burning. It can be treated whenever it flares up, and is non malignant. Most HPV's of this type are very common, harmless, non cancerous, and easily treatable. Genital warts are known technically as condylomata acuminatum and are generally associated with two HPV types, numbers 6 and 11 and can be sexually transmitted.

Cervical Cancer and Oral Cancer
There are other forms of HPV which are also sexually transmitted, and are a serious problem. These are; HPV-16, HPV-18, HPV-31, and HPV-45. These cancer-associated types of HPVs cause dysplastic tissue growths that usually appear flat and are nearly invisible. Dysplastic tissue is the presence of abnormal cells on the surface of the skin. Dysplasia is not cancer, but it is a tissue change seen prior to malignancy. A highly studied topic is HPV's ability to cause cervical cancer. Dysplasia can be detected on the female cervix through a Pap smear test, or seen visually using a magnifying glass called a colposcope. The most dangerous HPV's, 16 and 18, which are transmitted through sexual contact are known to cause up to 95% of cervical cancers. Now these two HPV's are also being linked to oral cancer.

A study done by Dr. No-Hee Park showed that the mouth was, at the cellular level, structurally very similar to the vagina and cervix. Both organs have the same type of epithelial cells that are the target of HPV 16 and HPV 18. The majority of oral cancers are cancers of epithelial cells, primarily squamous cell carcinomas, not unlike the cancers that affect the cervix. Dr. Park's study also showed that smoking and drinking alcohol help promote HPV invasion.. Combine tobacco and alcohol with HPV, and the epithelial cells in the mouth, and you may have the formula for the development of an oral cancer.

A recent study conducted by Dr. Maura Gillison at the Johns Hopkins Oncology Center furthered the premise that HPV is linked with certain types of oral cancer. In 25% of 253 patients diagnosed with head and neck cancers, the tissue taken from tumors was HPV positive and HPV 16 was present in 90% of these positive HPV tissues. This information helps to confirm that there is a strong link between HPV 16 and oral cancer. 25% of those diagnosed with oral cancer are non-smokers while the other 75% of those diagnosed have used tobacco in some form during their lifetimes. The research into the relationship of HPV and oral malignancies may give us clues as to the origin of cancer in those 25% of diagnosed individuals who did not smoke. Further research is being conducted into the relationship of HPV with oral cancers.

Human papillomavirus: its identity and controversial role in oral oncogenesis, premalignant and malignant lesions

Int J Oncol. 2007 Apr;30(4):813-23.  Human papillomaviruses (HPVs) are a group of host-specific DNA viruses, with a remarkable epithelial cell specificity: they have been reported principally in the ano-genital tract, urethra, skin, larynx, tracheo-bronchial and oral mucosa. More than 100 different HPV types have been identified and classified as high (e.g. 16, 18, 31) or low (e.g. 11, 42, 36) -risk (HR and LR), based on their association with cervical carcinoma. The carcinogenic role of HR-HPV revolves mainly around two of its oncoproteins: HPV-E6 which promotes degradation of the p53 tumour suppressor gene product and HPV-E7 which modifies the pRb tumour suppressor gene product, inhibiting the activity of TGF-beta2. Since these viral oncoproteins are capable of transforming primary human keratinocytes from either genital or upper respiratory tract epithelia, they have been considered to play a role in disrupting cell-cycle regulatory pathways leading to a genetic progression to ano-genital cancer and, possibly, also to oral squamous cell carcinoma (OSCC). Recently, the oncogene HPV-E5 has also been found to transform cells by modulating growth factor receptors. On the basis of the high, although very variable, frequency of HR-HPV in OSCC, an oral malignant potential of HPV infection has been hypothesised but not definitively confirmed.

Human papillomavirus infection as a prognostic factor in carcinomas of the oral cavity and oropharynx.

Int J Cancer. 2003 Apr 10;104(3):336-44./

Although studies have established human papillomaviruses (HPVs) as a risk factor for oral and oropharyngeal cancer, it is not clear whether viral infection affects survival in head and neck malignancies. This investigation examined the relationship between HPV and survival in carcinomas of the oral cavity and oropharynx. Formalin-fixed, paraffin-embedded tumor specimens from 139 newly diagnosed cases were tested for HPVs by PCR and DNA sequencing. Patient and tumor characteristics were obtained from questionnaires, pathology reports and cancer registries. Odds ratios (ORs) and relative risks (RRs) were based on logistic and Cox regression models, respectively. HPVs were detected in 21% of the tumors; 83% were HPV-16. Greater risk of HPV infection was associated with males (OR = 2.9), a history of oral-genital sex (OR = 4.2), and oropharyngeal tumors (OR = 10.4). As tobacco usage increased, the odds of HPV detection decreased (OR = 0.97/pack-year). HPV infected patients had better overall survival (RR = 0.3) than those with HPV-negative tumors. There was an interaction between gender and HPV for overall (p = 0.05) and disease-specific (p = 0.03) survival that suggested that HPV infected males had better prognosis than HPV-negative males, but this was not the case among females. HPV status was identified as an independent prognostic factor in oral and oropharyngeal cancers. This result appeared to be gender-specific, suggesting the need for further study of the interaction between HPV and gender on survival.

Human papillomavirus-16 in oral squamous cell carcinoma: clinical correlates and 5-year survival.

 Br J Oral Maxillofac Surg. 2007 Mar;45(2):116-22. Epub 2006 Jun 15.     We examined 66 oral squamous cell carcinomas (OSCCs) for human papillomavirus-16 (HPV-16) infection to evaluate its prognostic significance. Cox regression analysis of 5-year survival demonstrated that patients without nodal metastasis or with intratumoural HPV-16 showed better prognoses compared with each counterpart. In Kaplan-Meier survival analysis, nodal status but not HPV-16 status was statistically significant. The 5-year survival rate of HPV-16 positive patients without nodal metastasis (94%) was extremely high, compared with that of HPV-16 negative patients with nodal metastasis (25%). These results suggest that HPV-16 status as well as nodal status may provide prognostic significance in patients with OSCC.