Head and Neck Squamous Cell Carcinomas in HIV-Positive Patients: A Preliminary Investigation of Viral Associations

Abstract

Oncogenic human papillomaviruses (HPVs) are associated with oropharyngeal squamous cell carcinoma (SCC). Infection with human immunodeficiency virus (HIV) increases susceptibility to opportunistic infections and viral-promoted cancers. The prevalences of HPV, herpes simplex virus (HSV), Epstein-Barr virus (EBV), and human herpesvirus-8 (HHV-8) have not been established for head and neck squamous cell carcinoma in HIV-positive patients (HIV+ HNSCC). We have observed that HIV+ HNSCC tend to contain numerous multinucleated tumor giant cells, this finding has not been described previously. The goal of this study is to test for these oncogenic viruses in a small cohort of retrospectively identified patients with HIV infection, and to compare histologically these cancers to a control group of HNSCC patients. Tumors were reviewed histologically and compared to a control group of 102 patients with HNSCC (serologically untyped or HIV negative). Polymerase chain reaction (PCR) was performed on formalin-fixed, paraffin-embedded HIV+ HNSCC samples from combined 25 patients in two institutions. In situ hybridization was performed to identify EBV (EBER) and immunohistochemistry was performed to detect HSV-1, HSV-2, HHV-8, and HIV-related proteins (Nef, p24). The study sample consisted of 34 HIV+ patients with HNSCC from Montefiore Medical Center, and six HIV+ HNSCC patients from Hospital Clinic, University of Barcelona; 24 (60%) men and 16 (40%) women. The larynx was most commonly involved (65%, n = 26); followed by the oropharynx (22.5%, n = 9). Four carcinomas arose from the oral cavity (10%) and one from the nasal cavity (2.5%). Histologically, multinucleated tumor giant cells were more common in the HIV+ group (39/40, 97.5%) than the control group (27/102, 26%, p 0.001, chi-square). HPV was detected in 6 of 25 (24%) HNSCC tumors by PCR, five were typed as HPV 16 and one as HPV 26/69; five of these tumors (83%) were located in the oropharynx. EBV, HSV-1, HSV-2, and HHV-8 were detected only infrequently in tumor cells. Nef protein was detected in tumor cells in 7 of 21 (33.3%) cases; p24 was not detectable in 6 tumors studied. There were no significant associations between HPV positive tumors and co-infections with other viruses. This study is consistent with other reports that suggest an increased incidence of laryngeal carcinoma for HIV+ patients. HPV was detected in 24% of HIV+ HNSCC, however, the number of tumors with amplifiable DNA (n = 25) is too small to allow for conclusions. EBV, HSV-1, HSV-2, and HHV-8 are uncommon in HIV+ HNSCC; it is unlikely that these viruses have a promoting effect. MNTCG are significantly common in HIV+ HNSCC, but there is overlap in MNTCG counts with the control group and therefore this finding cannot be used as a biomarker of HIV infection.

Human papillomavirus infection in oral fluids of HIV-1-positive men:prevalence and risk factors

“…In the United States, a study was conducted with 190 HIV-positive men, and found that 6.3% them had detectable HPV in their oral fluid samples23. On the other hand, a study conducted in theUnited States and Spain with 166 patients showed a prevalence of 21% of oral HPV in HIV-positive MSM individuals, of which 11.1% were low-risk types and 66.6% were high-risk types24. In our study, oral HPV infection was detected in 3.5% of HIV-positive patients, in accordance withboth previous results and with the variability found in the prevalence of oral HPV in several studies9.…”

When is chemotherapy in head and neck squamous cell carcinoma not indicated?

“…Although the known association with oncogenic human papillomavirus (HPV) with oropharyngeal HNSCC has led some to speculate viral co-infection as an explanation for the increased risk of HNSCC in HIV-positive populations, preliminary data from HNSCC specimens of these patients have not clearly supported this hypothesis [36]. Concerns of using systemic therapies for this population include risks of immunosuppression and increased toxicity; however, limited evidence suggests that appropriately selected patients can tolerate organ-preserving therapy [37,38].…”

Human Papillomavirus (HPV) Biomarkers in Head and Neck Squamous Cell Carcinoma (HNSCC)

“…2). These primers amplify DNA fragments in the L1 region encoding the hypervariable V loop of the major capsid protein generating a fragment size approximately 450 and 150 bp (McLemore et al 2010). Several types of PCR-based detection for HPV have evolved over the past decade.…”