Human papillomavirus and oropharyngeal squamous cell carcinoma: what the clinician should know

The incidence of oropharyngeal squamous cell carcinoma (OPSCC) is rising in contrast to the decreasing incidence of carcinomas arising in other subsites of the head and neck. The human papillomavirus (HPV) infection has played an increasing role in these epidemiological changes and as the etiology for a significant fraction of head and neck squamous cell carcinomas, OPSCC in particular. Most importantly, many retrospective studies have shown that the prognosis differs significantly between patients with HPV-associated tumors and non-HPV associated tumors. Thus, questions arise on the choices of treatment for patients based on HPV status and the consequences of therapy. Given the recognized relevance of HPV status in OPSCC, many new questions concerning the biology, treatment, and prevention of HPV infection arise. This review is intended to highlight some of the major issues and frequently asked questions relevant for the clinician dealing with patients with OPSCC.     

Human papillomavirus co-infection and survival in oral and oropharyngeal squamous cell carcinoma: A study in 235 Brazilian patients

ObjectivesWhile unknown for oropharyngeal squamous cell carcinoma (OPSCC) and oral squamous cell carcinoma (OSCC), some studies assessing cervical carcinoma have shown that human papillomavirus (HPV) co-infection can be associated with its prognosis.MethodsThrough in situ hybridization (HPV and Epstein-Barr virus [EBV] probes) and immunohistochemistry (p16^INK4a, cyclin D1, p53, and Ki-67 antibodies), 126 OPSCC and 109 OSCC samples were assessed.ResultsAll patients were EBV-negative. OPSCC (25%) showed a significant association with HPV compared to OSCC (11%). Almost all HPV-associated cases were p16^INK4a-positive. Regarding OPSCC and OSCC, 23 and 7 cases were positive for high-risk HPV (HRHPV) only, 6 and 3 cases for low-risk HPV (LRHPV) only, and 3 and 2 cases for HRHPV/LRHPV, respectively. HPV-associated carcinomas showed a significantly higher proliferative index than HPV-unassociated carcinomas. Both carcinomas showed a similar overall survival rate, which was not affected by the HPV status. However, when comparing HPV-associated subgroups, patients with HRHPV/LRHPV-associated carcinomas showed worse survival.ConclusionLRHPV-associated and HRHPV/LRHPV-associated cases can also be detected when assessing OSCC and OPSCC. Further studies, especially in populations with a high prevalence of HPV-associated OPSCC, are necessary to understand the clinicopathological behavior of these neoplasm subgroups.     

Inverted papilloma and squamous cell carcinoma.

Since 1960, 15 patients with histologically proven inverted papilloma of the nose and paranasal sinuses have been treated at the University Hospital, City Hospital, and V. A. Hospital in Boston. Eight of these patients have been found to have squamous cell carcinoma in the pathological specimens; four of these patients have died of carcinoma. Wide surgical excision, usually through a lateral rhinotomy with exenteration of the invaded sinus as indicated, was the therapy of choice. In spite of the published incidence of carcinoma in inverted papilloma of approximately 7-24 per cent, we have found a much higher rate. We therefore, suggest that meticulous microscopic examination of multiple sections of inverted papilloma specimens be carried out in a search for evidence of squamous cell carcinoma. Inverted papilloma should be treated as a premalignant lesion by appropriate radical surgery.     

Use of quantitative diffusion-weighted magnetic resonance imaging to predict human papilloma virus status in patients with oropharyngeal squamous cell carcinoma

Although identification of human papilloma virus (HPV) status in oropharyngeal squamous cell carcinoma (OPSCC) is essential in predicting treatment response, no imaging modality can currently determine whether a tumor is HPV-related. In this retrospective study, 26 patients with OPSCC confined to the lateral wall or the base of tongue underwent neck magnetic resonance imaging, using T1-, T2- and diffusion-weighted imaging (DWI). Apparent diffusion coefficients (ADCs) in a region of interest covering the largest available primary tumor area of OPSCC on a single slice of the ADC map were calculated using two b values (0 and 1,000 s/mm²). Mean and minimum ADCs were compared with HPV status, using p16 immunohistochemistry as a surrogate marker for HPV infection. Mean and minimum ADCs for HPV⁺ OPSCC were significantly lower than those for HPV^? OPSCC. A cut-off value of mean ADC for HPV⁺ OPSCC of 1.027 × 10^?3 mm²/s yielded sensitivity and specificity of 83.33 and 78.57 %, respectively. In conclusion, the present study indicates that ADC could be used to predict HPV status in patients with OPSCC.     

Distant cutaneous metastasis from oropharyngeal squamous cell carcinoma

Squamous cell carcinoma is the most common malignant neoplasm of the upper aerodigestive tract. The disease is characterized by frequent lymphatic spread; however, blood-borne distant metastasis is rare. Isolated cutaneous metastasis is even rarer. We present two cases of oropharyngeal carcinoma that presented with cutaneous metastasis in the absence of disease recurrence. Both patients were treated with wide excision of the metastatic nodule and were disease-free at the 1.5-year follow-up. This article highlights the importance of cutaneous metastasectomy.     

Human papilloma virus and carcinoma of the laryngopharynx

The presence of human papillomavirus (HPV) genomes 6, 11, 16 and 33 in 16 patients with laryngopharyngeal carcinomas was examined by means of a polymerase chain reaction. HPV genomes were detected in 75 per cent of cases. In hypopharyngeal carcinoma, HPV 6 and 11 were present in adjacent tissue but absent from the tumour. HPV 16 and 33 were present in 40 per cent of laryngeal tumours and adjacent tissue. These results suggest that HPV 16 and 33 may be closely associated with the development of some laryngopharyngeal carcinomas.     

A clinical analysis of sinonasal squamous cell carcinoma: a comparison of de novo squamous cell carcinoma and squamous cell carcinoma arising from inverted papilloma

Abstract

Background: Sinonasal squamous cell carcinoma (SCC) is a rare tumor arising either de novo or in association with inverted papillomas (IPs).

Objectives: The aim of this study was to investigate and compare the oncological features and prognosis of patients with sinonasal SCCs based on their etiology.

Material and methods: The medical records of 117 patients who had been diagnosed with de novo SCC or those arising from IP (IP-SCC) were retrospectively reviewed. In situ hybridization analyses to detect HPV 16/18DNA and p16 immunohistochemistry were also performed in 10 cases with IP-SCC.

Results: The three-year disease-specific survival (DSS) rate was higher in cases with T1, 2 and 3 than in cases with T4 in both tumor groups. T4 cases with de novo SCC had a better DSS than those with IP-SCCs. HPV16/18 was not detected in any of the 10 IP-SCCs.

Conclusions and significance: T4 cases with de novo SCC tended to have a better DSS than those with IP-SCC. Since some T4 patients with IP-SCC were found to have a highly aggressive disease, careful treatment planning should be performed. High-risk HPV may not play a vital role in the carcinomatous transformation of most IP-SCC cases.     

Tumor volume as a prognostic factor in oropharyngeal squamous cell carcinoma treated with primary radiotherapy

Objectives/Hypothesis: Tumor volume has been demonstrated to play a prognostic role in many head and neck cancers. The purpose of this study was to conduct an institutional review analyzing the correlation between tumor volume and locoregional control of oropharyngeal squamous cell cancer treated with primary radiotherapy. Study Design: Retrospective institutional chart analysis. Methods: Seventy‐nine patients from 1991 to 2005 with primary T1 to T4 oropharyngeal squamous cell carcinoma (base of tongue, n = 31; soft palate, n = 1; tonsils, n = 47) were treated with primary radiotherapy. Tumor volumes were measured from pretreatment computerized tomography scans by two observers. Three‐dimensional tumor volumes were calculated using a computer digitizer for each computed tomography slice showing the primary lesion. Survival analysis, using the methods of Kaplan and Meier, was performed to assess whether tumor volume, Tumor, Node, Metastasis classification, tumor stage, or location were associated with locoregional failure. Results: Tumor volume did not significantly correlate with locoregional failure (observer 1, P = .6244; observer 2, P = .5612). There was a high interobserver correlation (r = 0.98970). Univariate analysis did, however, demonstrate a significant difference in locoregional failure between T4 tumors and all other T stages (T1 vs. T4, P = .0107; T2 vs. T4, P = .0004; T3 vs. T4, P = .0155). Nodal status, tumor stage, and location did not significantly correlate with locoregional failure rate. Conclusions: Tumor volume does not appear to play a significant role in predicting locoregional recurrence for patients with primary squamous cell cancer of the oropharynx treated with primary radiotherapy. However, T4 status was predictive of poor locoregional control.     

口咽部鳞状细胞癌人乳头状瘤病毒感染预后初步分析

目的 分析人乳头状瘤病毒( human papillomavirus,HPV)感染与口咽鳞状细胞癌(简称鳞癌)患者的预后关系.方法 回顾性分析1999年1月至2009年12月符合入组条件的口咽鳞癌患者共66例,利用聚合酶链反应方法检测其标本HPV感染状态.Kaplan-Meier法分析患者总体生存率和疾病特异性生存率与HPV感染状态的关系,Cox模型进行多因素分析.结果 口咽癌患者HPV总感染率为16.7％ (11/66),其中,HPV-16型7例,HPV-16/11、HPV-35、HPV-58/52和HPV-33/52/54型各1例.随访3 ～78个月,中位时间24.5个月.本组患者3年总体生存率为59.4％,HPV阳性组为90.0％,HPV阴性组为52.4％;3年疾病特异性生存率为63.0％,HPV阳性组为90.0％,HPV阴性组为56.4％,HPV阳性患者两组生存率均明显高于HPV阴性者(x2分别为5.792和4.721,P值分别为0.016和0.030).Cox回归分析结果显示,有无HPV感染状态和N分级是影响口咽部鳞癌预后的独立危险因素(P值均＜0.01).结论 口咽部鳞癌患者HPV感染率为16.7％.HPV阳性的口咽鳞癌患者预后优于HPV阴性组患者,有无HPV感染是影响预后的独立危险因素.     

Human papilloma virus (HPV) antigens in lesions of laryngeal squamous cell carcinomas

Paraffin sections from 36 laryngeal squamous cell carcinomas with histological features of coexistent condylomatous changes (the flat, inverted and papillomatous lesions caused by human papilloma virus; HPV) were stained for HPV antigens with an indirect immunoperoxidase technique. The HPV antiserum used was prepared in guinea pigs immunized against the purified HPV virions from human common wart tissue. Of the tumors studied, 36% showed the presence of HPV antigens. In that, one-third of the flat and inverted lesions and 42% of the papillomatous lesions contained cells with intranuclear HPV-staining reaction. The role of HPV as the etiologic agent of laryngeal squamous cell papillomas is discussed, as is the potential malignant transformation of them. Based on the present results, the previously expressed view on the probable role of HPV in the development of laryngeal squamous cell carcinoma seems to gain further substantiation.     

The role of human papilloma virus infection in the etiology of oropharyngeal carcinoma

PURPOSE OF REVIEW: Evidence is growing that human papilloma virus is responsible for a subset of head and neck carcinomas. This review analyzes the history and current thinking regarding this relatively new etiologic agent of squamous cell carcinoma. RECENT FINDINGS: Research over the past year has confirmed that human papilloma virus is associated with subset of head and neck squamous cell carcinoma, especially tumors arising from the tonsil. Human papilloma virus 16 is the most common strain found in these tumors. Most studies also indicate that patients with human papilloma virus infection are more likely to have a better prognosis, engage in riskier sexual behavior, and have a history of less tobacco and alcohol consumption than patients who have human papilloma virus-negative tumors. Not all studies confirm these findings, however, and human papilloma virus, even the high-risk strains (16, 18, and 33) are found in a certain percentage of healthy individuals. SUMMARY: Human papilloma virus (especially strain 16) has been recognized as a probable etiologic agent for some head and neck squamous cell carcinomas. Most commonly, human papilloma virus is associated with tumors arising from the tonsillar epithelium. Because a definitive causal relationship is still to be identified, current research aims to delineate the specific mechanism whereby human papilloma virus produces squamous cell carcinoma. It is hoped that a vaccine may be produced in the near future that will serve as adjuvant therapy for patients with human papilloma virus-positive tumors.