HPV-Related Nonkeratinizing Squamous Cell Carcinoma of the Oropharynx: Utility of Microscopic Features in Predicting Patient Outcome

Abstract

Human papilloma virus (HPV) is an etiologic agent in a subset of oropharyngeal squamous cell carcinomas (SCCs). The aim of this study was to sub-classify SCC of the oropharynx based upon histologic features into nonkeratinizing (NK) SCC, keratinizing (K) SCC, and hybrid SCC, and determine the frequency of HPV and patient survival in each group. Patients with oropharyngeal SCC with a minimum of 2 years of clinical follow-up were identified from radiation oncology databases from 1997 to 2004. All patients received either up front surgery with postoperative radiation or definitive radiation based therapy. In situ hybridization (ISH) for high-risk HPV subtypes and immunohistochemistry for p16, a protein frequently up-regulated in HPV-associated carcinomas, were performed. Overall and disease-specific survival were assessed. Of 118 cases, 46.6% were NK SCC, 24.6% K SCC and 28.8% hybrid SCC. NK SCC occurred in slightly younger patients that were more often male. It more frequently presented with lymph node metastases and was surgically resected compared to K SCC. NK SCC was significantly more likely to be HPV and p16 positive than KSCC (P < 0.001) and to have better overall and disease-specific survival (P = 0.0002; P = 0.0142, respectively). Hybrid SCC was also more likely than K SCC to be HPV and p16 positive (P = 0.003; P = 0.002, respectively) and to have better overall survival (P = 0.0105). Sub-classification of oropharyngeal SCC by histologic type provides useful clinical information. NK SCC histology strongly predicts HPV-association and better patient survival compared to K SCC. Hybrid SCC appears to have an intermediate frequency of HPV-association and patient survival.

Ciliated Adenosquamous Carcinoma: Expanding the Phenotypic Diversity of Human Papillomavirus-Associated Tumors

“…Given the non-keratinizing morphology seen in these AsqCA, it appears reasonable to expect that, similar to oropharyngeal and papillary sinonasal non-keratinizing SCC, these may also harbor HPV DNA. Thus, HPV testing and/or p16 immunostaining can be used as ancillary data to further support a surface (or tonsillar crypt epithelium) derivation for a tumor, and in the example of cases 5-7, suggest the oropharynx as the primary site for a nodal metastasis [13][14][15][16][17]. Given limited materials on many of our cases, further subtyping of the HPV present was not possible.…”

Sinonasal Squamous Cell Carcinoma: A Review with Emphasis on Emerging Histologic Subtypes and the Role of Human Papillomavirus

“…These have been reviewed elsewhere [21], but summarizing their results (Table 1), for NKSCC the rate was 40.9 %, which is much lower than for oropharyngeal SCC [22]. From the data, one can see that, while there is a very close (almost implicit) relationship between NKSCC (as strictly defined) and HPV in oropharyngeal SCC [23,24], this is not the case for sinonasal NKSCC. For KSCC, only 4.0 % of tumors are related to transcriptionally-active HPV.…”

Adenosquamous Carcinoma of the Head and Neck: Relationship to Human Papillomavirus and Review of the Literature

“…These tumors may present as different variants distinct from the typical keratinizingtype SCC, including nonkeratinizing [5,6], basaloid [7,8], and papillary SCC [9] and also undifferentiated carcinoma [10]. It has also been documented in several studies that HPV-related carcinomas of the upper aerodigestive tract have more favorable prognosis than HPV negative ones [11][12][13].…”

“…It has also been documented in several studies that HPV-related carcinomas of the upper aerodigestive tract have more favorable prognosis than HPV negative ones [11][12][13]. Most previous studies investigated HPV in tumors using DNA-based polymerase chain reaction (PCR) [14] while in more recent years DNA-based in situ hybridization (ISH) has been used [5,13,15]. However, it is becoming increasingly recognized that HPV can be present without necessarily being biologically active, such that mere presence of the virus (as detected by these methods) may not indicate biological/clinical significance.…”