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While human papillomavirus (HPV) is most notable for its involvement in cervical cancer,1 it should also be understood that HPV lesions are commonly found in the oral cavity as well. Several studies have demonstrated a connection between HPV and oral cancer, which has tremendous relevance in patient care, including treatment and prevention of disease.

Benign oral HPV lesions are mostly asymptomatic and may persist or relapse spontaneously. The first part of this exercise will explain how to diagnose and treat some of the most common HPV-associated lesions of the oral cavity. The remainder of the discussion will investigate various links between certain HPV strains and oral cancer.

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Common Oral HPV Lesions

Squamous papilloma. The most common benign epithelial neoplasm of oral epithelium, squamous papilloma lesions may be found anywhere in the mouth with a predilection for the ventral tongue and frenum area, palate, and mucosal surface of the lips.2 Oral papillomas can be recognized by their small fingerlike projections, resulting in an exophytic lesion with a rough or cauliflowerlike verrucous surface (Figure 1). These lesions often have a white appearance and can occur in any age group. Squamous papilloma lesions are thought to be induced by HPV 6 or 11.3 The typical treatment is surgical excision. All lesions resembling a squamous papilloma are recommended for excision at the base (1-mm margin) to the depth of the submucosa.4 Removal should also be considered the cure. Recurrence or appearance of new lesions suggests the possibility of retransmission of a condyloma acuminatum or a carcinoma.4

Verruca vulgaris. Also known as the common wart, verruca vulgaris the most prevalent HPV skin lesion, but it can also be found in the oral cavity. This lesion is usually associated with HPV 2 and 4. In the mouth, verruca vulgaris is found most commonly on the keratinized surfaces of the gingiva and palate.2 Verruca vulgaris lesions are contagious, and it is thought that some oral lesions occur following autoinoculation. These lesions are typically found in children but can be seen in any age group. Verruca vulgaris lesions often rapidly enlarge (average size <5 mm) and then remain stable, very often for several years. It is not vital clinically to differentiate a verruca vulgaris lesion from a squamous papilloma since treatment is the same (surgical excision).

Focal epithelial hyperplasia. Also known as Heck disease, focal epithelial hyperplasia is associated with HPV 13 and 32 and was originally diagnosed in the Inuit population. Heck disease frequently affects children but is increasingly seen in the HIV-positive population as well. This lesion is typically located in the labial, buccal, and lingual mucosa. Focal epithelial hyperplasia lesions usually resemble the normal mucosal color but may occasionally appear white and papillary (Figure 2). Clinically, one would find multiple soft, smooth, dome-shaped papules measuring 3 mm to 10 mm and lacking a pebbly surface. The lesions often persist for many months or even years and spontaneously resolve with no treatment. The risk of recurrence is minimal.2

Condyloma acuminatum. Normally, condyloma acuminatum lesions are found in the genital area and are considered a sexually transmitted disease. Oral condylomas are associated with HPV 2, 6, and 11. Clinically, these lesions are similar in appearance to papillomas but are usually larger in size and are more clustered. Also, condylomas are known to be more diffuse and deeply rooted then papillomas. These lesions are most commonly found on the labial mucosa, soft palate, and lingual frenum. Condylomas arise through oral sex as well as by autoinoculation or as a result of maternal transmission. Most often, condylomas in the oral cavity are related to oral-genital contact. When these lesions are diagnosed in children, the examining clinician should be aware that their presence may be an indication of sexual abuse, and the appropriate authorities should be notified.2 Condylomas can cause disfigurement and are difficult to treat. It is best to surgically remove all of the lesions simultaneously to lessen the probability of autoinoculation. Excision with lasers may lead to spread of the virus via airborne particles and is not advised. Podofilox (Condylox), an antimitotic topical agent used to treat genital and anal condylomas, has not been approved by the FDA for oral use but may be effective in treating oral condylomas.

Link between HPV and oral cancer

The possible link between certain HPV types and oral and orophyrangeal carcinomas is of great importance to clinicians. HPV has a clearly defined role in almost all cases of cervical cancer. The similarity of the morphologic features of genital and oral HPV-associated lesions was one of the early findings that suggested HPV might be involved in oral and laryngeal squamous cell carcinomas (SCCs).5 HPV 16 and 18 are the most commonly detected high-risk types.6 Human papillomavirus has been identified with increasing frequency in the progression from normal mucosa, through dysplasia, to carcinoma, but detection rates vary depending on the sensitivity of the assays used. In most studies, HPV DNA has been found in 25%-35% of oral carcinomas.7 Certain HPV genes code for proteins that can bind and inactivate the products of the tumor-suppressor genes p53 and Rb (retinoblastoma gene). Mutation or inactivation of these genes from any cause is thought to be a significant step in the development of oral cancer.6 Therefore, HPV is likely an important cofactor in some types of oral carcinoma.