HLA class I and II expression in oropharyngeal squamous cell carcinoma in relation to tumor HPV status and clinical outcome.

HPV-DNA positive (HPVDNA+) oropharyngeal squamous cell carcinoma (OSCC) has better clinical outcome than HPV-DNA negative (HPVDNA-) OSCC. Current treatment may be unnecessarily extensive for most HPV+ OSCC, but before de-escalation, additional markers are needed together with HPV status to better predict treatment response. Here the influence of HLA class I/HLA class II expression was explored. Pre-treatment biopsies, from 439/484 OSCC patients diagnosed 2000-2009 and treated curatively, were analyzed for HLA I and II expression, p16(INK4a) and HPV DNA. Absent/weak as compared to high HLA class I intensity correlated to a very favorable disease-free survival (DFS), disease-specific survival (DSS) and overall survival (OS) in HPVDNA+ OSCC, both in univariate and multivariate analysis, while HLA class II had no impact. Notably, HPVDNA+ OSCC with absent/weak HLA class I responded equally well when treated with induction-chemo-radiotherapy (CRT) or radiotherapy (RT) alone. In patients with HPVDNA- OSCC, high HLA class I/class II expression correlated in general to a better clinical outcome. p16(INK4a) overexpression correlated to a better clinical outcome in HPVDNA+ OSCC. Absence of HLA class I intensity in HPVDNA+ OSCC suggests a very high survival independent of treatment and could possibly be used clinically to select patients for randomized trials de-escalating therapy.

Survival in patients with human papillomavirus positive tonsillar cancer in relation to treatment.

The incidence of tonsillar cancer and the proportion of human papillomavirus (HPV) positive tonsillar cancer cases have increased in the last decades. In parallel, treatment for tonsillar cancer has been intensified e.g., by accelerated radiotherapy, and chemotherapy, resulting in more side effects. Patients with HPV-positive tonsillar cancer have better prognosis than those with HPV-negative tumors, and the former group could hypothetically benefit from reduced, less-toxic treatment without compromising survival. Here, we therefore evaluated possible differences in overall and disease-specific survival after different oncological treatments in 153 patients with HPV DNA- and P16-positive tonsillar cancer who were diagnosed and treated with intent to cure between 2000 and 2007, in Stockholm, Sweden. Of these patients, 86 were treated with conventional radiotherapy, 40 were treated with accelerated radiotherapy and 27 were treated with chemoradiotherapy. There were no significant differences in overall or disease-free survival between the groups. However, there was a trend, implying a beneficial effect of the intensified treatment, with chemoradiotherapy being better than radiotherapy despite that more patients had stage IV disease in the former group; and accelerated radiotherapy being better than conventional radiotherapy. This needs to be followed further in larger more homogenous groups of patients. In conclusion, patients with HPV-positive tonsillar cancer treated with conventional- or accelerated radiotherapy or chemoradiotherapy disclosed similar survival rates. The trend for better survival and less metastasis after intensified treatment underlines the need for large prospective studies comparing less intense to more intense treatment (chemoradiotherapy).

Human papillomavirus and survival in patients with base of tongue cancer.

The incidence of base of tongue cancer is increasing in Sweden and the proportion of human papillomavirus (HPV) positive cancer has increased in Stockholm, Sweden. Between 2006 and 2007, 84% of base of tongue cancer cases in Stockholm were HPV-positive. The objective of this study was to assess the impact of HPV status on prognosis for base of tongue cancer patients. One-hundred and nine patients were diagnosed with base of tongue cancer between 1998 and 2007 in Stockholm County and 95 paraffin-embedded diagnostic tumor biopsies were obtained and tested for HPV by PCR. Eighty-seven patients had available biopsies, were treated with intention to cure and could be included in the survival analysis. Age, sex, TNM-stage, stage, treatment and survival were recorded from patient charts. Kaplan-Meier curves were used to present survival data. In multivariable analyses, a Cox proportional hazards model was used to adjust for covariates. In total 68 (78%) tumor biopsies from the 87 included patients were HPV DNA positive. Kaplan-Meier estimates showed that the overall survival for patients with HPV-positive cancer was significantly better (p = 0.0004), (log-rank test) than that of patients with HPV-negative cancer. Patients with HPV-positive tumors also had significantly better disease-free survival (p = 0.0008), (log-rank test) than those with HPV-negative tumors. These results further strengthen the option to consider HPV-status when planning prospective studies on treatment for base of tongue cancer.

Ligasure versus diathermy scissors tonsillectomy: A controlled randomized study.

CONCLUSIONS: Ligasure tonsillectomies took longer than bipolar diathermy scissors tonsillectomies. Peroperative haemostasis was comparable in the two groups. Postoperative haemorrhage was higher than expected, which needs to be further investigated. A new handpiece, specifically designed for tonsillectomy, could probably improve surgical performance regarding operative time. OBJECTIVE: To compare tonsillectomy using Ligasure with bipolar diathermy scissors with regard to operative time, blood loss and complications. METHODS: This was a prospective study; 150 patients (> 15 years of age) undergoing tonsillectomy were randomized to tonsillectomy using either Ligasure or bipolar diathermy scissors. Operative time, peroperative blood loss, postoperative pain and complications were recorded and evaluated. RESULTS: A total of 149 cases were included, 75 randomized to Ligasure tonsillectomy and 74 to bipolar diathermy scissors tonsillectomy. Peroperative blood loss was similar in both groups. On average the operative time was 8 min longer in the Ligasure group. Postoperative pain was similar in the two groups. Twenty patients (13%) experienced postoperative haemorrhage, which is higher than our previous material. Slightly fewer patients experienced postoperative haemorrhage in the Ligasure group compared with the diathermy scissors group but the difference was not significant. Two of the 20 patients that experienced postoperative haemorrhage required a return to theatre to stop the bleeding, fewer than previously observed. No other complications were seen.

The role of human papillomavirus in the increased incidence of base of tongue cancer.

Numerous reports have shown that the incidence for oropharyngeal cancer is increasing and that human papillomavirus (HPV) is a risk factor. However, few studies have investigated the specific subsites of the oropharynx. Following our previous research on tonsillar cancer, we assessed the increase in the incidence of base of tongue cancer and the prevalence of HPV in this disease. Between 1998 and 2007, 109 patients were diagnosed for base of tongue cancer in Stockholm county. Ninety-five paraffin-embedded diagnostic tumor biopsies from patients were obtained and tested for HPV, both by general HPV PCR and HPV-16/HPV-33 type-specific PCR. Expression of HPV-16 RNA was analyzed to confirm E6 and/or E7 expression. Incidence data were obtained from the Swedish Cancer Registry. An overall increase in the incidence of base of tongue cancer from 0.15/100,000 person-years during 1970-1974 to 0.47/100,000 person-years during 2005-2007 was found in Sweden. The prevalence of HPV in base of tongue cancer in Stockholm county increased from 58% during 1998-2001 to 84% during 2004-2007 (p < 0.05). In the HPV-positive tumors, HPV-16 dominated (86%) but interestingly, HPV33 was detected in as many as 10%. E6 and/or E7 RNA were found in 85% of the samples tested. The incidence of base of tongue cancer, as well as the proportion of HPV-positive tumors, has increased in Sweden during the study period, suggesting that HPV may contribute to this increase.

A 4-year consecutive study of post-tonsillectomy haemorrhage.

OBJECTIVE: To analyse consecutive material over a period of 4 years concerning the incidence and consequences of post-tonsillectomy haemorrhages (PTH). DESIGN: Prospective study. SETTING: University hospital. PARTICIPANTS: All non-oncological cases of tonsillectomy (TE) and adenotonsillectomy (TA) performed at the ENT department at the Karolinska University Hospital between March 2000 and April 2004. MAIN OUTCOME MEASURES: Rate, timing and classification of PTH. RESULTS: During the study period, 2,813 cases (mean age 13 + or - 12.8 years; SD) of TE and TA were included. The majority (62%) were children aged below 12 years, and 69% were performed as day surgery. In total, 212 (7.5%) patients were readmitted due to PTH, of which 98 (3.4%) presented with ongoing haemorrhage. The rates of primary and secondary bleeding were 1.9 and 5.5%, respectively. The PTH occurred in 0-19 days post-operatively, in a typical twin peak mode around the day of surgery and then days 4-7. No case of serious PTH was noted. Multiple bleedings (2-3 times) occurred in 19 patients. Only a minority (31%) of the single PTH patients required active treatment, surgery in the theatre (35 patients) or diathermy under local anaesthesia in the emergency room (24 patients). However, almost all received systemic haemostatic treatment. Three patients required blood transfusion due to repeated PTH. Of the 114 patients that did not present with an active PTH, only 1 returned to the operating theatre due to later bleeding. Almost half (43%) of the patients with multiple episodes of PTH had also experienced primary bleedings. CONCLUSIONS: A primary PTH seems to indicate a risk of further episodes of bleedings, and should necessitate extra post-operative observation. Patients with a history of a single self-limiting PTH showed low risk of developing a haemorrhage requiring return to the theatre.

Incidence of human papillomavirus (HPV) positive tonsillar carcinoma in Stockholm, Sweden: an epidemic of viral-induced carcinoma?

In the county of Stockholm, between 1970 and 2002, we have previously reported a 3-fold parallel increase in the incidence of tonsillar squamous cell carcinoma (SCC) and the proportion of human papillomavirus (HPV) positive tonsillar SCC. Here, we have followed the above parameters in all patients (n = 120) diagnosed with tonsillar SCC during 2003-2007 in the same area, and also in correlation to our previous data. Ninety-eight pretreatment biopsies were available and presence of HPV DNA and HPV-16 E6 and E7 RNA were tested by polymerase chain reaction (PCR) and RT-PCR. Incidence data were obtained from the Swedish Cancer Registry. Data reported from 1970 to 2002 were also obtained for comparison. HPV DNA was present in 83 of 98 (85%) of the tonsillar SCC biopsies from 2003 to 2007 and 77 of these were HPV-16 positive. HPV-16 E6 and E7 RNA were found in 98% of 52 analyzed HPV-16 positive cases. The proportion of HPV-positive cancers had significantly increased both from 1970 to 2007 (p < 0.0001) as well from 2000 to 2007 (p < 0.01), with 68% (95% confidence interval (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 and 2007, in parallel with a decline of HPV-negative tumors. In conclusion, the incidence of HPV-positive cancers is still increasing in the County of Stockholm, suggesting an epidemic of a virus-induced carcinoma, with soon practically all tonsillar SCC being HPV positive, as in cervical cancer.