Human Papillomavirus (HPV) 16 E6 Variants in Tonsillar Cancer in Comparison to Those in Cervical Cancer in Stockholm, Sweden

Background: Human papillomavirus (HPV), especially HPV16, is associated with the development of both cervical and tonsillar cancer and intratype variants in the amino acid sequence of the HPV16 E6 oncoprotein have been demonstrated to be associated with viral persistence and cancer lesions. For this reason the presence of HPV16 E6 variants in tonsillar squamous cell carcinoma (TSCC) in cervical cancer (CC), as well as in cervical samples (CS), were explored. Methods: HPV16 E6 was sequenced in 108 TSCC and 52 CC samples from patients diagnosed 2000–2008 in the County of Stockholm, and in 51 CS from young women attending a youth health center in Stockholm. Results: The rare E6 variant R10G was relatively frequent (19%) in TSCC, absent in CC and infrequent (4%) in CS, while the well-known L83V variant was common in TSCC (40%), CC (31%), and CS (29%). The difference for R10G was significant between TSCC and CC (p = 0.0003), as well as between TSCC and CS (p = 0.009). The HPV16 European phylogenetic lineage and its derivatives dominated in all samples (.90%). Conclusion: The relatively high frequency of the R10G variant in TSCC, as compared to what has been found in CC both in the present study as well as in several other studies in different countries, may indicate a difference between TSCC and CC with regard to tumor induction and development. Alternatively, there could be differences with regard to the oral an

Chromosomal aberrations and aneuploidy in oral potentially malignant lesions: distinctive features for tongue

<p>Abstract</p> <p>Background</p> <p>The mucosae of the oral cavity are different at the histological level but appear all equally exposed to common genotoxic agents. As a result of this exposure, changes in the mucosal epithelia may develop giving rise to Oral Potentially Malignant Lesions (OPMLs), which with time may in turn progress to Oral Squamous Cell Carcinomas (OSCCs). Therefore, much effort should be devoted to identify features able to predict the likeliness of progression associated with an OPML. Such features may be helpful in assisting the clinician to establish both appropriate therapies and follow-up schedules. Here, we report a pilot study that compared the occurrence of DNA aneuploidy and chromosomal copy number aberrations (CNAs) in the OPMLs from different oral anatomical subsites.</p> <p>Methods</p> <p>Samples from histologically diagnosed OPMLs were processed for high resolution DNA flow cytometry (hr DNA-FCM) in order to determine the relative DNA content expressed by the DNA index (DI). Additionally, array-Comparative Genomic Hybridization (a-CGH) analysis was performed on DNA obtained from diploid nuclei suspensions directly. When aneuploid nuclei were detected, these were physically separated from diploid nuclei on the base of their DI values by means of a DNA-FCM-Sorter in order to improve the a-CGH analysis.</p> <p>Results</p> <p>Tongue OPMLs were more frequently associated with DNA aneuploidy and CNAs than OPMLs arising from all the other mucosal subsites.</p> <p>Conclusions</p> <p>We suggest that the follow-up and the management of the patients with tongue OPMLs should receive a distinctive special attention. Clearly, this hypothesis should be validated in a prospective clinical study.</p

Frequency of HPV-associated tonsillar cancer in Sweden

6030 Background: Numerous studies has shown an increase of the incidence of tonsillar squamous cell carcinoma (SCC) both in the USA and in Sweden. This increase in incidence is despite a decreasing prevalence in smoking, a well-known risk factor for developing tonsillar cancer. The proportion of human papillomavirus (HPV) positive tonsillar SCC has also been shown to increase. This study aims to examine the incidence of tonsillar SCC and the proportion of HPV positive tonsillar SCC between 2003–2007 in the County of Stockholm, Sweden in correlation to data from 1970–2002. Methods: All patients (n = 120) diagnosed with tonsillar SCC during 2003–2007 in the County of Stockholm were included in this study. Ninety-eight pre-treatment biopsies were available and presence of HPV DNA and HPV-16 E6 and E7 mRNA were tested by PCR and RT-PCR. Incidence data between 2003–2007 for Sweden and in the County of Stockholm was obtained from the Swedish Cancer Registry. Data reported from 1970 to 2002 was also obtained for comparison. Results: HPV DNA was present in 83/98 (85%) of the tonsillar SCC biopsies from 2003–2007. Of the 77 HPV-16 positive tumors, HPV-16 E6 and E7 mRNA were found in 98% of the analyzed cases. The proportion of HPV-positive cancers had significantly increased both from 1970 to 2007 (p &lt; 0.0001) as well from 2000 to 2007 (p &lt; 0.01), with 68% (95% CI, 53–81) 2000–2002; 77% (95% CI, 63–87) 2003–2005; and 93% (95% CI, 82–99) 2006–2007. The incidence rate of HPV-positive tumors almost doubled each decade between 1970–2007, in parallel with a decline of HPV-negative tumors. Conclusions: Today, almost all tonsillar SCC in the County of Stockholm is HPV positive, and the incidence of HPV-positive cancers is still increasing. The data suggest that we are dealing with an epidemic of a virus-induced carcinoma, and that soon practically all tonsillar SCC will be HPV positive; a similar situation observed in cervical cancer. No significant financial relationships to disclose. </jats:p