Human papillomavirus (HPV) is absent in branchial cleft cysts of the neck distinguishing them from HPV positive cystic metastasis

Background: Distinguishing branchial cleft cysts (BCCs) from cystic metastases of a human papillomavirus (HPV) positive oropharyngeal squamous cell carcinoma (OPSCC) is challenging. Fine needle aspirates (FNAs) from cystic metastasis may be non-representative, while reactive squamous cells from BCC can be atypic. Based on cytology and with the support of HPV DNA positivity many centers treat cystic metastasis oncological and thus patients are spared neck dissection. To do so safely, one must investigate whether HPV DNA and p16^INK4a overexpression is found exclusively in cystic metastases and not in BCC.

Patients and methods: DNA was extracted from formalin fixed paraffin embedded (FFPE) surgically resected BCCs from 112 patients diagnosed 2007–2015 at Karolinska University Hospital and amplified by PCR. A multiplex bead-based assay used to detect 27 HPV-types and p16^INK4a expression was analyzed by immunohistochemistry (IHC).

Results: All 112 BCCs were HPV DNA negative, and of 105 BCCs possible to evaluate for p16^INK4a, none overexpressed p16^INK4a.

Conclusions: HPV DNA and p16^INK4a overexpression were absent in BCCs. Lack of HPV DNA and p16 protein overexpression in BCCs is helpful to discriminate benign BCCs from HPV⁺ OPSCC metastasis. HPV testing definitely has a role in the diagnostics of cystic masses of the neck.     

Humane Papillomviren bei Plattenepithelkarzinomen der Kopf- und Halsregion

Human papilloma viruses (HPV) are responsible for approximately half of all oropharyngeal squamous cell carcinomas (OPSCC) and incidence rates of HPV-associated OPSCC continue to increase substantially. The defined viral carcinogenesis permits development of specific diagnostic, therapeutic, and prophylactic approaches. Laboratory identification of HPV-associated OPSCC may be achieved by p16^INK4a immunohistochemistry combined with HPV DNA detection by polymerase chain reaction (PCR) using tumor tissue. Patients with HPV-associated OPSCC have a relatively good prognosis; therefore, the HPV status plays an important role in patient guidance. Due to the relatively favorable prognosis, ongoing studies are evaluating whether less rigorous therapy for HPV-positive patients results in equally good cure rates. The criteria for patient selection are, however, still uncertain. Particularly markers for detection of HPV-positive patients with a high risk of treatment failure are lacking. Besides tumor stage and comorbidities, distinct genomic, epigenetic, and immunologic alterations are prognostically relevant for HPV-associated OPSCC, and might be of predictive value. Furthermore, the characteristic molecular alterations suggest the possibility of novel vigilant and specific therapy approaches. These may be inhibitors of the phosphatidylinositol 3?kinase (PI3K) pathway, which is frequently activated in HPV-associated OPSCC, and immunotherapeutic methods, e.?g., therapeutic vaccination. Although prophylactic HPV vaccinations may also prevent development of HPV-associated OPSCC, foreseeable effects on OPSCC incidence will be low, given the low vaccination rates in Germany. This highlights the fact that interdisciplinary research networks should enhance the necessary activities related to HPV-associated OPSCC.     

Update zu HPV-assoziierten Kopf-Hals-Karzinomen – Highlights der ASCO-Jahrestagung 2018

Rising incidence rates in human papillomavirus (HPV)-associated oropharyngeal squamous cell carcinoma (OPSCC) and a significantly improved prognosis have brought this entity into scientific focus. At this year’s American Society of Clinical Oncology (ASCO) Annual Meeting, 291 studies with the keyword “HPV” were presented, the majority of which were in head and neck cancer. Due to high rates of late toxicities after conventional therapy, de-intensified treatment concepts are being increasingly discussed, although data from prospective phase III studies were not presented. Retrospective data on the latest TNM staging (downstaging in many HPV-associated patients) and other risk stratification systems were presented. HPV diagnostics based solely on p16 immunohistochemistry were discussed. Many groups presented work on the HPV association and its prognostic relevance not only in oropharyngeal carcinoma, but also in oral cavity, hypopharyngeal, and locally advanced laryngeal squamous cell carcinoma. New prognostic biomarkers such as methylation signatures appear to be promising. New data suggest equal survival rates in HPV-associated stage I OPSCC treated with surgery alone in comparison to patients who received adjuvant therapy after surgery. A possible negative effect on overall survival in stage III HPV-associated OPSCC with a cisplatin dose ≤200?mg/m² was discussed. Results of de-escalation studies are urgently awaited, in order to be able to treat HPV-associated OPSCC patients as precisely and as specifically as possible and ensure long-term quality of life.     

Presenting symptoms and clinical findings in HPV-positive and HPV-negative oropharyngeal cancer patients

Objectives: Oropharyngeal squamous cell carcinoma (OPSCC) is divided in two different disease entities depending on HPV involvement. We investigated differences in presenting symptoms and clinical findings in patients with HPV-positive and -negative OPSCC tumors.

Methods: Altogether 118 consecutive patients diagnosed with primary OPSCC between 2012 and 2014 at the Helsinki University Hospital were included. HPV-status of the tumors was assessed by PCR detection of HPV DNA and immunostaining with p16-INK4a antibody.

Results: Fifty-one (47.7%) of the patients had HPV-positive and 56 (52.3%) HPV-negative tumors. Forty-nine (49/51, 96.1%) of the HPV+ tumors were also p16+ showing high concordance. The most common presenting symptom among HPV+/p16+ patients was a neck mass (53.1%), whereas any sort of pain in the head and neck area was more frequently related to the HPV?/p16? (60.0%) group. HPV+/p16+ tumors had a tendency to locate in the tonsillar complex and more likely had already spread into regional lymph nodes compared with HPV?/p16? tumors. Smoking and heavy alcohol consumption were significantly more common among HPV?/p16? patients but also rather common among HPV+/p16+ patients.

Conclusions: This analysis of symptoms and signs confirm that OPSCC can be dichotomized in two distinct disease entities as defined by HPV status.     

Analysis of exon 2 of MTS1 in HPV-positive and HPV-negative tumors of the head and neck region

The aim of this study was to investigate the role of human papillomaviruses (HPVs) and alterations of p16INK4A in different squamous cell carcinomas (SCCs) of the head and neck region by screening these carcinomas for alterations in exon 2 of p16INK4A and for HPV DNA. A total of 42 samples of different SCCs of the head and neck were collected by biopsy or surgical resection. After DNA isolation, exon 2 of p16 was amplified and sequenced. HPV DNA was detected by applying a broad-spectrum polymerase chain reaction system. Mutations were found in 4 of our 42 samples. A total of 27 biopsies showed the presence of HPV DNA. All of the biopsies showing a mutation in exon 2 of CDK4 were HPV –positive, except the first biopsy of an oropharyngeal carcinoma. It might be possible that HPV infection and mutations in the exon 2 of CDK4 play a causal role in malignant transformation in a small number of squamous carcinomas of the head and neck region.     

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.     

Tumor stromal desmoplasia and inflammatory response uniquely predict survival with and without stratification for HPV tumor infection in OPSCC patients

Abstract

Background: Oropharyngeal squamous cell carcinoma (OPSCC) positive for human papillomavirus (HPV) increases wolrd wide.

Aims/objectives: The objective for this study has been to evaluate tumor phenotypes and tumor host responses with respect to five-year disease-specific survival (DSS) in HPV(+) and HPV(?) patients.

Material and methods: Two hundred patients with OPSCC have been treated between 1992 and 2010. Histopathology slides from these patients have been morphologically evaluated in formalin-fixed, paraffin-embedded (FFPE) stained with hematoxylin–eosin (HE). From HE-stained sections tumor phenotype (keratinization, fraction of mature cancer cells and pattern of invasion) and tumor host responses (inflammation and stromal desmoplasia) were evaluated with respect to five years DSS.

Results: High tumor inflammatory response and low stromal desmoplasia had an independent effect predicting better five-year DSS among all patients and when analyzed separately in the HPV(?) and HPV(+) cohort of patients using a Cox regression survival analysis that also included standard clinical prognostic variables among OPSCC patients.

Conclusion: Tumor host responses, inflammation and stromal desmoplasia may become part of routine work-up in OPSCC patients due to prognostic value.

Significance: We present a method, accessible in most clinical locations and would give important additional information about prognosis in OPSCC patients.     

Correlation between HPV status at T and N sites of oropharyngeal squamous cell carcinomas

Objectives: Human papilloma virus (HPV) is known to be associated with oropharyngeal squamous cell carcinomas (OPSCC) and may potentially play a vital role in tumor metastasis. The purpose of this study was to correlate HPV status of cervical lymph node metastases with their respective primary OPSCC tumor.

Methods: Formalin-fixed, paraffin-embedded (FFPE) tissue samples obtained from 34 patients with cervical lymph node metastases were analyzed with HPV 16 DNA polymerase chain reaction (PCR), p16 immunohistochemistry and HPV typing. The results were correlated with the HPV status and type found in the primary tumors of OPSCC.

Results: Comparing HPV DNA status with p16 we found that 21 primary tumors and lymph node metastases were HPV positive (61.8%) and seven primary tumors and lymph node metastases were HPV negative (20.6%). Six patient samples differed when correlating the primary tumor and lymph node metastasis (17.6%).

Conclusions: In this study, HPV status in OPSCCs and their cervical lymph node metastases correlated in the vast majority of cases. However, HPV detection methods may have certain limitations resulting in varying degree of non-correlation. This should be taken into account when stratifying treatment in regard to HPV status.     

The quantitative analysis of the human papillomavirus DNA load in submandibular gland lesions with droplet digital polymerase chain reaction

Background: The relationship between infection with human papillomavirus (HPV) and tumorigenesis of salivary gland remains controversial.

Objectives: This study explored the relationship between HPV and salivary gland lesions as well as that of the HPV infection status and p16^INK4A immunoreactivity. The HPV DNA loads were also quantitatively evaluated.

Materials and Methods: Tissue samples from 31 submandibular gland lesions were evaluated. p16^INK4A immunohistochemical (IHC) staining, nested polymerase chain reaction (PCR), DNA sequencing, and droplet digital PCR (ddPCR) were performed.

Results: Non-neoplastic lesion, benign tumors, and malignant tumors were noted in 9, 16, 6 cases, respectively. p16^INK4A immunoreactivity was higher in malignant tumors than in benign tumors (50.0% vs. 6.3%). Single PCR with MY09/11 found that all samples were negative. Nevertheless, nested PCR revealed a high HPV-DNA positivity rate of 96.8%. No relationship between the HPV status and p16^INK4A immunoreactivity was shown. HPV-18 was the only subtype identified in this study. ddPCR showed significantly lower HPV-18 DNA loads in submandibular gland lesions than in oropharyngeal cancers.

Conclusions: HPV-DNA positivity and p16^INK4A-immunoreactivity were not correlated in submandibular gland lesions. The loads of HPV DNA detected in this study were small. HPV positivity therefore may not be associated with tumorigenesis of the submandibular gland.     

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.     

Basics of tumor development and importance of human papilloma virus (HPV) for head and neck cancer

Head and Neck Squamous Cell Carcinoma (HNSCC) are the 6th most common cancers worldwide. While the incidence of larynx-hypopharynx carcinoma decreases, actually an increase in oropharyngeal squamous cell carcinoma (OSCC) is observed. Classical risk factors for HNSCC are smoking and alcohol. Though, it was shown recently for 25 to 60% of OSCC, to be associated with an infection by oncogenic human papilloma virus (HPV). The development of "common" head-neck-tumors is substantially enhanced by an accumulation of genetic changes, which lead to an inactivation of tumor suppressor genes or to an activation of proto-oncogenes. A more or less uniform sequence of different DNA-damages leads to genetic instability. In this context, an early and frequent event is deletion on the short arm of chromosome 9, which results in inactivation of the p16-gene. On the contrary, for HPV-induced carcinogenesis, expression of the viral proteins E6 and E7 is most important, since E6 and E7 lead to inactivation of the cellular tumor-suppressor-proteins p53 and Rb. The process of natural transoral infection is not yet clear. However, as a matter of fact peroral HPV-infection is not seldom and in most cases such an infection heals completely and uneventfully. Smoking seems to increases the probability for developing an HPV-associated tumor. The association of HNSCC with HPV can be proven with established methods in clinical diagnostics. In addition to classical prognostic factors, diagnosis of an HPV-association may become important for future therapies. Prognostic relevance of HPV probably surmounts many known risk-factors, for instance regional metastasis. Until now, no other molecular markers are established in clinical routine. Future therapy concepts may vary for the two subgroups of patients, especially patients with HPV-associated OSCC may take advantage of a less aggressive postoperative treatment. Finally an outlook will be given on possible target-aimed therapies, of which so far only antibodies against EGF-receptors are established in clinical practice.     

Clinical and molecular characteristics of HNSCC patients with brain metastases: a retrospective study

Among the metastasis patterns of head and neck squamous cell carcinoma (HNSCC), intracranial spread is a rare but dreaded event. To date only very few cases have been reported and clinical and molecular data are sparse. We screened our archives for HNSCC patients from 1992 to 2005 who were diagnosed with brain metastases (BM). For retrospective analysis, all clinico-pathological data including disease-free survival (DFS), local progression-free survival (LPFS), and overall survival (OS) were compiled. Additionally, we assessed the mutational status of the TP53 gene and the prevalence of HPV serotypes by PCR and Sanger sequencing. Immunohistochemistry was applied to detect p16INK4A expression levels as surrogate marker for HPV infection. The prevalence rate of BM in our cohort comprising 193 patients with advanced HNSCC was 5.7 %. Of 11 patients with BM, 3 were female and 9 were male. Seven of the primary tumors were of oropharyngeal origin (OPSCC). LPFS of the cohort was 11.8 months, DFS was 12.1 months and OS was 36.0 months. After the diagnosis of BM, survival was 10.5 months. Five tumors showed a mutation in the TP53 gene, while five of the seven OPSCC tumors had a positive HPV status displaying infection with serotype 16 in all cases. Compared with patients who harbored TP53wt/HPV-positive tumors, patients with TP53 mutations showed a poor prognosis. Compared with the whole cohort, the interval between diagnosis of the primary and the detection of BM was prolonged in the HPV-infected OPSCC subgroup (26.4 vs. 45.6 months). The prognosis of HNSCC patients with BM is poor. In our cohort, most tumors were OPSCC with the majority being HPV positive. Our study points toward a putatively unusual metastatic behavior of HPV-positive OPSCC.     

人乳头状瘤病毒相关口咽鳞状细胞癌的特点及临床分析

目的 分析人乳头状瘤病毒（HPV）相关口咽鳞状细胞癌（OPSCC）的临床特点,探讨不同治疗方案对OPSCC患者生活质量的影响,以期更好地指导制定临床治疗方案并判断预后。方法 收集2014年1月-2019年1月在北京友谊医院诊治的38例OPSCC患者临床资料,男31例,女7例;其中扁桃体癌24例、舌根癌14例;HPV阳性患者13例,阴性患者25例;I、II期患者10例,III、IV期患者28例。38例患者中行同步放化疗4例,单纯根治性放疗2例,手术加术后放疗或放化疗27例,诱导化疗+术前放疗+手术或术后补充放疗5例。采用χ²检验分析HPV感染的临床特点,采用Kaplan-Meier法、Log-rank单因素分析和Cox回归模型多因素分析法计算生存率和预后相关因素分析;非参数秩和检验进行生活质量分析。结果 在OPSCC患者中,非吸烟、饮酒患者HPV阳性率更高（P=0.014,P=0.049）,HPV相关OPSCC患者更易发生颈部淋巴结转移（P=0.032）。HPV阳性以及肿瘤分期I、II患者总生存率更高（P=0.003,P=0.006）,且为影响患者预后的独立危险因素。3种治疗方案患者总生存率差异无统计学意义（P>0.05）,但同步放化疗患者吞咽功能障碍更显著,差异存在统计学意义（P=0.002）。结论 HPV相关OPSCC患者中多为非吸烟、饮酒的人群,更容易发生颈部淋巴结转移,但预后相对较好。可考虑降级治疗以保护患者的吞咽功能,改善治疗后的生活质量。     

Association of BMI-1 and p16 as prognostic factors for head and neck carcinomas

Conclusions BMI-1 is an upstream repressor of tumor suppressor p16 and their inverse expression patterns have been linked with patient survival in OPSCC. In this material only p16 remained a relevant prognostic marker in OPSCC.

Objectives HNSCC tumors carry variable phenotypes and clinical outcomes depending on their anatomical location. In OPSCC, expression of tumor suppressor p16 is used as a surrogate marker of HPV infection and has prognostic value. There are no good prognostic biomarkers for HNSCC tumors of other anatomical locations.

Aim To study the expression patterns of p16 and BMI-1 in not only oropharyngeal but also oral, hypopharyngeal, and laryngeal squamous cell carcinomas and to clarify their putative connections with clinical parameters, survival, and each other.

Method Hospital records on 130 patients (59 OPSCC, 18 OSCC, 20 HPSCC, and 33 LSCC) diagnosed between 1997–2008 at the Helsinki University Hospital, Finland, were reviewed. BMI-1 and p16 expressions were studied by immunohistochemistry.

Results Sixty-eight per cent of OPSCC expressed p16 and expression correlated with lower age, lower T- and higher N-category, and with improved OS and DFS. BMI-1 expression was most prevalent in OPSCC and LSCC, but had no clinical correlations. No correlation between p16 and BMI-1 expression was found.     

High-risk human papillomavirus (HPV) is not associated with p53 and bcl-2 expression in oral squamous cell carcinomas

Objective

To determine the frequency and type of human papillomavirus (HPV) in oral squamous cell carcinomas (OSCC), as well as to identify a possible association between HPV infection and the expression pattern of p53 and bcl-2, and identify whether the oral HPV infection is a characteristic finding in our sample.

Methods

We performed polymerase chain reaction and dot blot hybridization for the detection of HPV DNA in paraffin sections as well as immunohistochemical analysis of p53 and bcl-2 in our sample.

Results

Twenty-six cases (29.5%) were positive for the virus by PCR. Dot blot hybridization identified HPV 18 in 21 (80.8%) cases, HPV 16 in one (3.8%) case and a combination of the two types in the four (15.4%) remaining cases. No other type of HPV was detected in the sample. Immunohistochemistry showed p53 in 26 (60.4%) cases and bcl-2 in 17 (39.5%) ones. No significant association was observed between the presence of HPV and the expression of the proteins studied (p = 0.988 and p = 0.748, respectively).

Conclusions

Although this investigation have detected only 29.5% of HR-HPV DNA in OSCC, it is possible that this virus contribute to the development of some case of this tumor. Furthermore, it seems that the immunohistochemical expression of p53 and bcl-2 and the presence of HPV DNA are independent events in OSCC.     

Peri-tumoral infiltrate associates with postoperative prognosis of patients with OSCC: Stronger association in HPV negative patients

PurposeThe current data on the relationship between local inflammatory infiltration and prognosis in oral squamous cell carcinoma (OSCC) are limited and controversial, especially in different HPV status. In this study, we analyzed the relationship between peri-tumoral inflammatory infiltrate (PTI) and HPV status and prognosis of patients with OSCC after surgery.MethodsA retrospective cohort of 99 primary OSCC patients who underwent surgery was constructed. P16 immunohistochemistry was used to determine HPV status. PTI was determined by hematoxylin-eosin staining and quantified into four levels: none (Score 0), weak (Score 1), moderate (Score 2) and strong (Score 3). The associations of PTI with clinico-pathological characteristics, HPV status and survival were examined.ResultsMost OSCC patients had weak to moderate PTI. PTI was significantly associated with lymph node metastasis (P = 0.041), and patients with moderate PTI had significantly better OS (P = 0.009) than those with no PTI. In HPV negative OSCC, patients with moderate PTI also had significantly better OS (P = 0.019) than those with no PTI. However, PTI was not significantly associated with survival in HPV positive OSCC.ConclusionsIn HPV negative OSCC, moderate PTI may suggest a better postoperative prognosis than no PTI.     

Assessment of HPV 16, HPV 18, p16 expression in advanced stage laryngeal cancer patients and prognostic significance

IntroductionHuman papilloma virus is an etiological risk factor for a subset of head and neck squamous cell carcinomas. HPV has been proven to be a powerful prognostic biomarker for oropharyngeal cancer, but its role in the larynx has not been explored in depth. The developmental mechanisms of laryngeal carcinomas are quite complex and controlled by various factors. Smoking and alcohol are most important risk factors. Recent studies indicate that HPV infection also plays an important role in larynx carcinomas. HPV related laryngeal carcinomas especially occur at the supraglottic region of larynx.ObjectiveWe aimed to determine the frequency of HPV/protein16 positivity in patients with laryngeal carcinoma and association of HPV and/or p16 positivity with variables such as age, sex, smoking habits, tumor localization, lymph node metastasis, recurrence and survival in advanced stage laryngeal carcinoma in our study.MethodsThis retrospective study included 90 patients with advanced laryngeal carcinoma. The Control group was 10 normal larynx mucosa specimens. The presence of HPV was investigated polyclonally by polymerase chain reaction, and protein16 with immunohistochemical method. In HPV positive cases, the presence of HPV types 16, 18 were evaluated by polymerase chain reaction. Demographic features of patients were noted. Patient survival and association with HPV/protein16 was determined.ResultsPolyclonal HPV positivity was detected in 11 (12.2%) of 90 cases. Out of these 11 cases, HPV 16 was positive in 6, HPV 18 in 4, and both HPV 16 and 18 were positive in 1. In 18 (20%) of the cases, p16 was positive. Six of the cases (6.6%) had both HPV and protein16 positivity. In cases where protein16 alone or HPV and protein16 were co-positive, alcohol use was less and the tumor was found more likely to be localized in the supraglottic area. These ratios were statistically significant. Supraglottic localization of tumor was determined to be increased in protein16 positive cases. The correlation between protein16 positivity and supraglottic area location was determined to be statistically significant (p = 0.011). 55.6% of protein16 positive cases was located in the supraglottic region, 33.3% was glottic and 11.1% was transglottic. Although life expectancy over 5 years were numerically higher in HPV and protein16 positive cases, this was not found to be statistically significant. There was no statistically significant relationship between HPV positivity and mean age, differentiation, smoking and alcohol use, tumor progression, lymph node metastasis, localization, recurrence, cause of mortality and treatment methods in our study. The mean follow-up period of our patients was 6.7 years.ConclusionThe close relationship between HPV and oropharyngeal squamous cell carcinoma could not be shown in larynx malignancy in many studies, including our study. Our findings support a limited role of HPV in laryngeal carcinogenesis. Protein16 is not a reliable surrogate for HPV status in laryngeal cancers and is not a predictor of laryngeal cancer survival. Supraglottic localization of tumor was determined to be increased in protein16 positive cases. The correlation between protein16 positivity and supraglottic area location was determined to be statistically significant. There is a need for more populated clinical trials, where neoplastic proliferation is better demonstrated and the accuracy of the results obtained is supported by different techniques.     

Comparison of HPV prevalence in HNSCC patients with regard to regional and socioeconomic factors

HPV infection is considered as an independent risk factor for head and neck squamous cell carcinomas (HNSCC). Due to highly variable prevalence results in numerous studies, it is, however, difficult to estimate the relevance of HPV infection as risk factor for a specific patient collective. This study aimed to elucidate the disparities of HPV prevalence by analyzing socioeconomically and regionally different patient collectives. Two age, gender, stage and tumor location matched cohorts of 18 private health insured (PHIP) and 16 statutory health insured patients (SIP) suffering from an oropharyngeal squamous cell carcinoma (OSCC) and treated at a university hospital were screened for p16 overexpression and HPV infection by immunohistochemistry and PCR. In addition 85 HNSCC patients of an otolaryngology private practice (PPP) in a rural area were screened for p16 overexpression and positive cases were tested for HPV infection. HPV prevalence was 72.2 % in the PHIP collective in comparison to 25.0 % (p = 0.015) in the SIP collective with a significantly improved 5-year overall survival (p = 0.003) of the PHIP collective. The total HPV prevalence of PPP group was 7.1 % with the highest infection rate in tonsillar carcinomas (33.3 %) and a larger percentage of female patients in the HPV positive group (p = 0.037). This study shows that variable HPV infection rates in HNSCC can be caused by the selection of particular patient collectives, which suggest taking socioeconomic and regional factors into account for a decision on HPV testing, if it is not performed on a routine basis.     

Comparison of psychosocial factors over time among HPV+ oropharyngeal cancer and tobacco-related oral cavity cancer patients

Introduction

The role of human papilloma virus (HPV) in the pathogenesis of oropharyngeal squamous cell carcinoma (OPSCC) is well documented, as is the excellent prognosis of patients with HPV-associated disease; in contrast, oral cavity squamous cell carcinoma (OCSCC) is associated with tobacco and alcohol use and has a worse prognosis. While causative factors, staging, and treatment guidelines differ between these cancer subsets, few studies have compared psychosocial factors in these groups.

Is human papillomavirus involved in laryngeal neuroendocrine carcinoma?

The purpose of this study was to detect human papillomavirus (HPV) infection in laryngeal neuroendocrine carcinoma (LNEC) and to explore the possible relationship between HPV-induced malignant transformation and prognosis in LNEC. Ten cases of LNEC from a tertiary referral hospital were retrospectively analyzed. Clinical data were subtracted from patients’ files. Pretreatment biopsy material was tested for the presence of HPV6, 11, 16, and 18 using a PCR-based detection method. Immunohistochemical staining was performed for Ki-67, p16^INK4A, and p53 expression. All cases were negative for the low-risk HPV types HPV6 and HPV11 that are associated with laryngeal papillomatosis. High-risk HPV was detected in two cases; an atypical carcinoid was positive for HPV16 and a large-cell neuroendocrine carcinoma for HPV18. Both HPV-positive tumors had a high Ki-67 labeling index. Two of the four cases with a good response to therapy were hrHPV-positive (both HPV DNA positive) compared with none of the five poor responders. Our findings show that HPV may play a role in the pathogenesis of LNEC. The relationship between HPV, improved prognosis and good response to therapy for squamous cell carcinoma of the head and neck may also be true for a subset of LNEC.