Anders Näsman

Human papillomavirus is a favourable prognostic factor in tonsillar cancer and its oncogenic role is supported by the expression of E6 and E7

From 1970 to 2002 in the Stockholm area, we revealed a parallel three‐fold increase in the incidence of tonsillar cancer and the proportion of human papillomavirus (HPV) positive tonsillar cancer cases, indicating a possible role of HPV infection in this disease. We have now examined whether HPV and viral load in pre‐treatment tonsillar cancer biopsies correlates to disease prognosis, and whether the presence of HPV‐16 E6 and E7 mRNA could be ascertained. The presence of HPV‐16, but not viral load, in tonsillar cancer was shown to be a favourable prognostic factor for clinical outcome. Moreover, E6 and/or E7 were expressed in almost all assessable HPV‐16 positive cases, supporting an oncogenic role of HPV‐16 in tonsillar cancer.

Presence of human papillomavirus (HPV) in vulvar squamous cell carcinoma (VSCC) and sentinel node.

OBJECTIVE To investigate the presence of HPV in VSCC and sentinel nodes (SN) in patients in Sweden and the possible influence of HPV on prognosis. PATIENTS AND MATERIALS Primary tumors from 75 VSCC patients undergoing the SN procedure and SNs from 69 patients were tested for HPV DNA. Analyses were performed by PCR using general (GP5+/6+ and CPI/IIG) type-specific primers, and sequencing in paraffin-embedded VSCC and SN. RESULTS HPV was detected in 23/75 (31%) of the tumors and in 10/23 (43%) of the SNs in patients with HPV-positive tumors and in one SN of a patient with an HPV-negative tumor. Patients with HPV-positive VSCC were younger at diagnosis (p<0.001) and had better survival (p=0.030), adjusted for age and lesion size, than those with HPV-negative tumors. In patients with HPV-positive tumors, SNs with metastases were more frequently HPV positive (5/5) than those without metastases (5/18) (p=0.007). CONCLUSION The rate of 31% HPV-positive VSCC in Sweden is similar to other reports. As far as we know, HPV in SN in VSCC never been investigated previously. The differences in age, tumor size, prevalence of HPV in SN and survival of patients with HPV-positive and negative VSCC support the assumption that VSCC develops through two different pathways, with better survival for patients with HPV-positive tumors. Presence of HPV DNA in SN was related to metastatic disease but did not affect survival in this study.

Expression of LRIG1 is associated with good prognosis and human papillomavirus status in oropharyngeal cancer

Background:The incidence of human papillomavirus (HPV)-associated oropharyngeal cancer has increased rapidly during the past decades. HPV is typically associated with a favourable outcome; however, a need exists for new and more effective prognostic and predictive markers for this disease. Leucine-rich repeats and immunoglobulin-like domains (LRIG)-1 is a tumour suppressor protein that belongs to the LRIG family. LRIG1 expression has prognostic significance in various human cancers, including cervical cancer, where HPV is a key aetiological agent.Methods:The prognostic value of LRIG1 and LRIG2 immunoreactivity was investigated in tumour specimens from a Swedish cohort of patients with tonsillar and base of tongue oropharyngeal cancers, including 278 patients.Results:LRIG1 immunoreactivity correlated with disease-free survival and overall survival in univariate and multivariate analyses. Notably, patients with HPV-positive tumours with high LRIG1 staining intensity or a high percentage of LRIG1-positive cells showed a very good prognosis. Furthermore, LRIG1 expression correlated with HPV status, whereas LRIG2 expression inversely correlated with HPV status.Conclusions:Taken together, the results suggest that LRIG1 immunoreactivity could be a clinically important prognostic marker in HPV-associated oropharyngeal cancer.

Presence of human papillomaviruses and p16 expression in hypopharyngeal cancer

Patients with hypopharyngeal cancer have a 5‐year survival of only 15% to 30%. Human papillomavirus (HPV) is a risk factor and a favorable prognostic factor for oropharyngeal carcinoma and p16 has been suggested as a surrogate marker for HPV‐induced cancer. However, few studies have been performed on HPV and p16 in hypopharyngeal cancer.

Prevalence of human papillomavirus (HPV) types in cervical cancer 2003-2008 in Stockholm, Sweden, before public HPV vaccination.

Abstract Background. Human papillomavirus (HPV) infection is the major cause of cervical cancer, but the prevalence of different HPV types varies depending on geographical location and may change dramatically after introduction of HPV vaccination. Here, we aimed to gain some information regarding the recent prevalence of different HPV types, in cancer of the uterine cervix in the Stockholm region, before the introduction of public HPV vaccination in Sweden. Material and methods. From 215 diagnosed cervical cancer patients 2003–2008 at the Karolinska University Hospital, 160 pretreatment cervical cancer samples, including both squamous cell carcinomas (SCC) and adenocarcinomas (ADC) could be obtained. DNA was extracted from 154/160 of the SCC and ADC samples and assayed by Luminex Multiplex for 24 different HPV types, including 15 high-risk (HR), three putative HR and six low-risk types (LR). Results. We successfully analysed 154/215 (71.6%) of the locally diagnosed cases and found a high prevalence of HPV with 92.9% in all uterine cervix cancer cases, and 93.3% and 91.4 % in SCC and ADC, respectively. All HPV positive cases harboured HR types, either alone or as multiple infections. In SCC HPV16 dominated and together with HPV18 accounted for 69.7% of the cases, followed in prevalence by HPV33, 31 and 45. In ADC, HPV18 was more common than HPV16, and they were observed in all except one of the HPV positive samples. Conclusion. The prevalence of HPV16 and 18, followed by HPV33, 31 and 45 is high in SCC and ADC in the Stockholm region. Public HPV vaccination could potentially inhibit a large proportion of such tumours underlining the urgency to initiate HPV vaccination.

No evidence for human papillomavirus having a causal role in salivary gland tumors

BackgroundSalivary gland malignancies are a very heterogeneous group of cancers, with histologically > 20 different subtypes, and prognosis varies greatly. Their etiology is unknown, however, a few small studies show presence of human papillomavirus (HPV) in some subtypes, although the evidence for HPV having a causal role is weak. The aim of this study was to investigate if HPV plays a causal role in the development of different parotid salivary gland tumor subtypes.MethodsDNA was extracted from 107 parotid salivary gland formalin fixed paraffin embedded tumors and 10 corresponding metastases, and tested for 27 different HPV types using a multiplex bead based assay. HPV DNA positive tumors were stained for p16INK4a overexpression by immunohistochemistry.ResultsOne of the 107 malignant parotid salivary gland tumors (0.93%) and its corresponding metastasis on the neck were positive for HPV16 DNA, and both also overexpressed p16INK4a. The HPV positive primary tumor was a squamous cell carcinoma; neither mucoepidermoid nor adenoid cystic tumors were found HPV positive.ConclusionsIn conclusion, HPV DNA analysis in a large number of malignant parotid salivary gland tumors, including 12 different subtypes, did not show any strong indications that tested HPV types have a causal role in the studied salivary gland tumor types.