Link Between HPV Infection and Oral Cancer

What Diseases Are Linked to HPV Virus?

Human papillomavirus (HPV) infection in the last few decades has gained the attention of physicians, dental surgeons, and researchers as it is an endemic affecting public health due to its potential linkage to cause cancers. HPV infection has been recognized as a standard and frequent sexually transmitted disease affecting the genitals and oropharyngeal cavity. The increased incidence of HPV-linked squamous cell carcinoma (SCC) in the head and neck region is also attributed to this viral infection.

Epidemiologic data suggest that HPV infections are responsible for making an individual 14-fold more prone to oropharyngeal cancers, cancers of the tonsils, or affecting the base of the tongue more frequently. According to traditional research, the spread of genital and oral HPV infections has been linked to an increased number of partners or high-risk sexual behavior in the younger population. It is prevalent among adults between 20 to 60 years of age.

HPV infections can be mainly distinguished in their ability to be of a high-risk oncogenic type that can predispose the individual to the developmental of malignant lesions, anogenital cancers, and oral squamous cell carcinomas, and the second type of HPV infections has the potential to cause benign papillomas, warts, and hyperplasia in the same regions.

As per research for cervical HPV infections, the virus first penetrates the cutaneous layers of the hands and feet, consequently the mucosal surface of the upper aerodigestive tract and then the anogenital regions and the urethra. This may explain why people with persistent HPV infections may be predisposed to develop cervical or anogenital cancers.

How Is Oral HPV Classified?

The lesions in the oral mucosa may range from the flat, papular, or plaque-like structure that may be grayish, white, or reddish. Clinically, they may be asymptomatic or associated with trouble chewing or swallowing. The oral HPV infections can be grouped as follows:

• Benign Lesions.

• Focal epithelial hyperplasia.

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• Squamous cell papilloma.

• Verruca vulgaris, etc.

• Potentially Malignant Lesions.

• Oral erythroplakia.

• Oral lichen planus.

• Proliferative verrucous leukoplakia, etc.

• Malignant Lesions.

• Oral squamous cell carcinoma.

• Verrucous carcinomas.

What Is the Structure and Pathogenesis of HPV?

The HPV proteins are double-stranded DNA viruses surrounded by a material of icosahedral capsid. These capsid proteins are mainly composed of primary (L1) and minor (L2) capris proteins along with capsomeres. The viral replication by this cell machinery is a highly regulated process for the infection of the host cell by producing mature virion particles. Soon after the HPV cells infect the host cell body, the dynamic changes in the leukocytes right from the basal to the superficial layer in the orogenital regions cause a suitable microenvironment for this viral cell replication.

Specific HPV cell receptors (like alpha six integrin, heparan sulfate proteoglycans, and extracellular laminin 5) act to enter the viral pathogen into the host cells through micro-wounds of the epithelium. As the viral genome remains active, the infection spreads up the layers of the basal, parabasal, and then the higher layers of the epithelium with the formation of complete virions. The viral cells then finally undergo desquamation after being expelled from the epithelial layers and then transmitted by direct contact (as in the case of genital warts) or in the form of indirect contact as well.

What Is the Route of Spread?

Though the genital route of HPV infection spread remains sexual, that is due to sexual contact with an infected partner, cases of vertical transmission extending to virgins, infants, and children are also reported and possible. This vertical nonsexual transmission might be feasible as the virus gets inoculated and spreads through three main routes, namely:

• Periconceptual route - HPV transmission around the time of fertilization.

• Prenatal route - HPV transmission during pregnancy.

• Perinatal route - HPV transmission around the time after the birthing process.

How Are Oral HPV Lesions Treated?

HPV lesions genitally are treated by the gynecologist or the general physician suggest the following:

• Local or systemic administration of cytotoxic and immunomodulatory drugs for treating the infection (for example, Podophyllin, Podophyllotoxin, Cidofovir drug therapies, immunomodulatory drugs like Imiquimod, and targeted molecular therapies).

• For the elimination of genital lesions, surgical and ablative therapy with electrocautery, cold knife, or laser under local anesthesia may be performed.

• For lesions like anogenital warts and condylomas, cryosurgery, electrocautery, cryotherapy with liquid nitrogen, or lasers are used.

• The management of oral HPV infections is usually based upon the complete elimination of the virus by follow-up of the HPV DNA test in the patient after eight to 12 months following antiviral therapy.

• Tested antiviral drugs like Acyclovir and Ribavirin are proved to effectively reduce the viral load, as suggested by the physician.

Conclusion:

To conclude, HPV lesions need the earliest possible diagnosis and drug-based or surgical intervention by the oral surgeon and the gynecologist or physician to establish a long-term prognosis for these individuals and prevent these lesions from potentially developing into fatal cancers. In addition, the dental or maxillofacial surgeon can diagnose the HPV infection by oral sampling, which involves biopsy or cytology procedures to prevent and estimate the risk of oral cancers.