HPV-Related Squamous Cell Carcinoma Variants in the Head and Neck

Abstract

The great majority of HPV-related carcinoma of the oropharynx is nonkeratinizing squamous cell carcinoma. More recently, an increasing number of squamous cell carcinoma variants that are HPV positive are being reported in the oropharynx, as well as in other head and neck sites. As a result, several clinical and pathologic questions have emerged. Importantly, questions raised include whether the virus is biologically active and involved in the pathogenesis of these tumors, and whether there are clinical implications with regard to patient outcome and treatment modality changes that may be needed in HPV-related variants. Examples of HPV-related squamous cell carcinoma variants that will be addressed here include: basaloid squamous cell carcinoma, undifferentiated carcinoma, adenosquamous carcinoma, papillary squamous carcinoma, and small cell carcinoma. Some investigations have suggested a favorable prognosis in some variants, analogous to that of the conventional nonkeratinizing (basaloid) carcinoma, while others showed poorer outcome. So far, the number of studies on this subject is limited and the number of cases evaluated in each investigation is few. Because of this, it is prudent at this stage not to alter management protocols as a result of identification of HPV in these variants and to await additional studies.

Small Cell Neuroendocrine Carcinoma of the Oropharynx Harbouring Oncogenic HPV-Infection

“…Our search of the literature identified a limited number of articles documenting NECs of the oral cavity/oropharynx (including both primary and metastatic tumours). These include single case reports [4][5][6][7][8][9], small case series [10][11][12][13], and review articles [1,3,14,15]. The small number of reported cases has precluded definitive classification of primary oral/oropharyngeal NECs.…”

“…The possibility of metastasis from a distant primary tumour (most commonly pulmonary small cell carcinoma) should be considered [2,3]. The literature contains a relatively small number of articles reporting NECs arising of the oral cavity/oropharynx [1,[3][4][5][6][7][8][9][10][11][12][13][14][15]. Exposure to tobacco and alcohol are implicated in the aetiology of NECs arising in the oral cavity [3,11].…”

Papillary Squamous Cell Carcinoma of the Head and Neck

“…1-4 It is often confused with verrucous carcinoma and squamous cell carcinoma (SCC) with verrucous features. These 2 entities have broad-based exophytic projections and are characterized by excessive keratinization.…”

“…1 The majority of HPV-related SCCs of the oropharynx exhibit a nonkeratinizing (NK) morphology. 4,6,7 The neoplastic cells have an immature basaloid appearance and are mitotically active. Human papillomavirus (HPV) has also been identified in several head and neck SCC variants, including basaloid SCC, undifferentiated carcinoma, adenosquamous carcinoma, and, more recently, PSCC, particularly when they arise in the oropharynx but not exclusively.…”

“…Human papillomavirus (HPV) has also been identified in several head and neck SCC variants, including basaloid SCC, undifferentiated carcinoma, adenosquamous carcinoma, and, more recently, PSCC, particularly when they arise in the oropharynx but not exclusively. 1,4,6 However, to date, no studies have thoroughly and directly evaluated for transcriptional activity of the HPV or for the clinicopathologic significance of its presence in PSCC.…”