ABSTRACT
BACKGROUND: We aimed to clarify the possible role of human papillomavirus (HPV) infection in the malignant transformation of sinonasal inverted papilloma (IP). METHODS: Subjects comprised 32 patients with chronic rhinosinusitis (CRS), 17 with IP, 5 with IP and squamous cell carcinoma (IP + SCC), and 16 with primary sinonasal SCC. HPV presence, viral loads, and physical status were investigated using polymerase chain reaction. Retinoblastoma (pRb), p53, and p16(INK4a) gene products were investigated by immunohistochemistry. RESULTS: HPV DNA was detected in 6.3 % of cases with CRS, 29.4 % with IP, 40 % with IP + SCC, and 25 % with SCC. IP cases had significantly higher HPV presence than CRS cases (p = 0.04). High-risk HPV-16 was the most frequently encountered subtype (10/13, 76.9 %). HPV-16 viral loads varied from 2.5 to 7953 E6 copies/50 ng genomic DNA. Patients in the SCC and IP + SCC groups had significantly higher viral loads than those in the IP and CRS groups (p < 0.01). All SCC and IP + SCC patients with HPV-16 demonstrated mixed-type integration, whereas 4 of 5 HPV-16 patients in the IP and CRS groups showed episomal type infection (p = 0.04). Positivity to pRb was found in 78.1 % of CRS, 35.3 % of IP, and 68.8 % of SCC cases. The presence of HPV DNA negatively correlated with pRb expression in SCC (p = 0.029) and IP (P = 0.049) groups. Although 62.5 % of SCC cases exhibited p53 positivity, only 5.9 % of IP, and no CRS cases were positive. Regardless of HPV status, p16(INK4a) positivity was frequently detected in IP cases (82.4 %), less in SCC (12.5 %) cases, and was not detected in the CRS group. Neither the IP nor SCC cohorts showed any correlation between HPV presence and the expression of either p53 or p16(INK4a). CONCLUSIONS: HPV infection was more frequent in the IP, IP + SCC, and SCC groups than the CRS group. Higher viral loads and integration observed in the IP + SCC and SCC groups, and an inverse correlation between HPV presence and positive pRb indicated that persistent infection and integration play a part in tumorigenesis and malignant transformation in certain IP cases. However, p16(INK4a) is not a reliable surrogate marker for HPV infection in IP.
ABSTRACT
OBJECTIVES: To determine the origin of the acoustically evoked short latency negative response (ASNR), a peculiar V-shaped response at about 3 to 4 milliseconds found during auditory brainstem response recordings. Previous reports demonstrated that the ASNR is present only in ears with profound hearing loss under intense stimulation. It has already been excluded as any kind of artifact. The individuals with ASNR had good vestibular function in spite of their poor hearing, suggesting a relation between the ASNR and the vestibular system. The saccule and vestibular nuclei are hypothesized to be the sense organ and the generator of the response, respectively. The current study tested the saccular function for ears with ASNR and searched for ASNR in ears with a functionless cochlea. STUDY DESIGN: Prospective study. SETTING: Academic tertiary referral center. PATIENTS: Twenty patients with bilateral profound hearing loss, aged 6 to 62 years, including 16 cochlear implant recipients. Twelve healthy participants with normal hearing, aged 23 to 30 years, served as the control group. INTERVENTIONS: Recordings of vestibular evoked myogenic potential (VEMP) and auditory brainstem responses. MAIN OUTCOME MEASURES: The presence or absence of ASNR in ears with cochlear implants. The presence or absence and threshold of VEMP in ears with ASNR versus ears without ASNR. RESULTS: ASNR was recorded by sound stimulation from three ears with unaided cochlear implants, a model of functionless cochlea. VEMP was evoked by sound stimulation to all the nine ASNR ears without threshold difference from normal control ( > 0.05), implying normal saccular function for the ASNR ears. For the ears with profound hearing loss and absence of ASNR, about two thirds were considered to have saccular afunction because of absence of VEMP. The other third displayed VEMPs with higher threshold than normal control ( < 0.01), indicating saccular hypofunction. Furthermore, ASNR and VEMP were elicited from an ear diagnosed with semicircular canal hypofunction. CONCLUSIONS: It is clear that the presence of ASNR is dependent not on residual hearing but on normal saccular function. On the basis of these results, the authors believe ASNR to be saccular in origin.
