Head and neck host a milieu for multifactorial carcinogens, including tobacco smoking, alcohol consumption and viral infections. Human Papilloma Virus (HPV) infection has gained increasing attention as a major factor in driving neoplasms in head and neck tumors. The fact that HPV-related tumors comprise almost 80 % of oropharyngeal carcinomas [1,2] has led to a significant increase in the importance of viral detection using ancillary techniques. Non-keratinizing squamous cell carcinoma (NKSCC), especially the basaloid type, is the typical morphologic profile for HPV positive tumors; however, this morphologic fingerprint does not obviate the inclusion of other variants under the same class of tumors [3,4]. HPV positive tumors are well known to have favorable prognosis, fewer metastasis, and better response to therapeutic modalities compared to their HPV negative counterparts [5]. Therefore, HPV detection is compelling as it guides the treatment regimen and predicts clinical outcomes.

p16 plays an important role as a surrogate marker for HPV detection. Viral products: E6 and E7 inhibit the Retinoblastoma (Rb) protein that normally downregulates p16 in the cell cycle [2]. Dysregulation of this pathway grants HPV its oncogenicity without acquiring additional molecular alterations observed in smoking related squamous cell carcinomas (SCC) [1]. Consequently, the differences between HPV positive and HPV negative neoplasms expand beyond the epidemiologic and histopathologic manifestations to include molecular mechanism.

The overexpression of p16 is visualized by immunohistochemistry (>75 % nuclear expression of at least moderate intensity) [5,6]. The fact that HPV persists in metastases and recurrences; even after treatment, contributes to the usefulness of p16 stain in differentiating between primary and metastatic diseases, and even in identifying the tumor origin in lymph node metastases [1]. Recently, AJCC identified p16 as the preferred ancillary testing in such settings [6].

Sarcomatoid (spindle cell) carcinoma is a rare variant of SCC in the head and neck. It manifests as an exophytic mass in elderly men with smoking history [3]. Radiation is another risk factor for this variant of SCC. The rarity of these tumors makes diagnosis more challenging, and more so due to their diverse histologic appearance. Classically, these tumors are biphasic with areas of epithelial differentiation adjacent to the spindle cell component [7]. It has been speculated that the spindle cell component belongs to the spectrum of epithelial to mesenchymal transition [8]. Monophasic tumors with diminished epithelial differentiation can still be encountered to a lesser degree. The occasional presence of heterologous mesenchymal differentiation can cause major diagnostic difficulty [7]. Florid reactive myofibroblastic proliferation and granulation tissue are great mimics for spindle cell carcinoma [9].

Bone and Soft tissue sarcomas are rare mesenchymal tumors accounting for 1 % of the head and neck malignancies [5,10]. Although sarcomas demonstrate a variety of histopathologic features, they often have shared prognosis, outcome, and biological behavior [11]. The increased aggressiveness, recurrence, and metastasis of these tumors require a combination of multiple treatment modalities [11,12]. The significance and prevalence of p16 immunostaining in head and neck sarcomas is yet to be studied. To our knowledge, no prior study has investigated the presence of HPV in sarcomatoid carcinoma in comparison to true sarcomas in the head and neck. The goal of this study is to evaluate head and neck mesenchymal tumors and sarcomatoid carcinomas for p16 staining and the presence of HPV.