Human papillomavirus-mediated carcinogenesis and HPV-associated oral and oropharyngeal squamous cell carcinoma. Part 2: Human papillomavirus associated oral and oropharyngeal squamous cell carcinoma

Abstract

Human papillomavirus (HPV) infection of the mouth and oropharynx can be acquired by a variety of sexual and social forms of transmission. HPV-16 genotype is present in many oral and oropharyngeal squamous cell carcinomata. It has an essential aetiologic role in the development of oropharyngeal squamous cell carcinoma in a subset of subjects who are typically younger, are more engaged with high-risk sexual behaviour, have higher HPV-16 serum antibody titer, use less tobacco and have better survival rates than in subjects with HPV-cytonegative oropharyngeal squamous cell carcinoma. In this subset of subjects the HPV-cytopositive carcinomatous cells have a distinct molecular profile.In contrast to HPV-cytopositive oropharyngeal squamous cell carcinoma, the causal association between HPV-16 and other high-risk HPV genotypes and squamous cell carcinoma of the oral mucosa is weak, and the nature of the association is unclear.It is likely that routine administration of HPV vaccination against high-risk HPV genotypes before the start of sexual activity will bring about a reduction in the incidence of HPV-mediated oral and oropharyngeal squamous cell carcinoma.This article focuses on aspects of HPV infection of the mouth and the oropharynx with emphasis on the link between HPV and squamous cell carcinoma, and on the limitations of the available diagnostic tests in identifying a cause-and-effect relationship of HPV with squamous cell carcinoma of the mouth and oropharynx.

Association between human papillomavirus (HPV) and the oral squamous cell carcinoma: a systematic review

“…However, evidence warns that this finding is not a reliable prediction of HPV-induced neoplastic progression, as the determination of viral load does not distinguish between an infection of many cells containing few copies of viral DNA per cell and an infection of few cells with a large number of viral copies per cell, or even between long-standing infection and recent infection (10) .…”

“…These results, from studies of diverse designs, allow inferring the possibility of the cited virus participation in oral carcinogenesis, but direct experimental evidence establishing cause and effect is required for confirmation. For Feller et al (10) , it is necessary that a significant number of individuals harboring HPV in the oral mucosa develop carcinoma in a certain period, as can be seen in cases of squamous carcinoma of the uterine cervix. The presence of high-risk genotypes with confirmed expression of E6 and E7 oncoproteins in the malignant cells, both in the primary site and in metastases, and viral monoclonality are also decisive.…”

“…HPV infection in the oral cavity is associated with risky sexual behaviors, mainly to orogenital sex. However, mouth-to-mouth contact, vertical birthtransmission and autoinoculation resulting from chewing warts are also transmission modes of this virus to the oral mucosa (10) . The viruses isolated in OSCC are low-risk genotypes, including HPV- 6,11,16,18,22,31,33,35,38,58,68, and 70 (51) .…”

Genotipificación, niveles de expresión y estado físico del virus del papiloma humano en pacientes colombianos con cáncer de células escamosas en la cavidad oral

“…Los genes virales E6 y E7 son regulados negativamente por los genes virales E1 y E2, los cuales pueden fragmentarse ocasionalmente, lo cual produce la pérdida de control de la transcripción de las oncoproteínas E6 y E7 (19,20). Estos genes provocan la integración del genoma viral al ADN de las células del huésped, incrementando de esta forma la persistencia viral, mecanismo que opera principalmente en virus de alto riesgo (21,22). El ADN del HPV puede darse dentro de la célula humana de tres formas: integrado al genoma celular; libre en el núcleo celular, es decir, en forma episómica, y de forma mixta, es decir, integrada y episómica (21,23).…”

“…Estos genes provocan la integración del genoma viral al ADN de las células del huésped, incrementando de esta forma la persistencia viral, mecanismo que opera principalmente en virus de alto riesgo (21,22). El ADN del HPV puede darse dentro de la célula humana de tres formas: integrado al genoma celular; libre en el núcleo celular, es decir, en forma episómica, y de forma mixta, es decir, integrada y episómica (21,23).…”