Elimination of HPV-associated oropharyngeal cancers in Nordic countries.

Incidence of human papillomavirus (HPV, most notably HPV type 16) associated oropharyngeal squamous cell carcinoma (OPSCC) among middle-aged (50-69 year-old) males has tripled in four high income Nordic countries (Denmark, Finland, Norway and Sweden) over the last 30 years. In Finland and Sweden, this increase was preceded by an HPV16 epidemic in fertile-aged populations in the 1980's. The recent implementation of school-based prophylactic HPV vaccination in early adolescent boys and girls will gradually decrease the incidence, and eventually eliminate the HPV-associated OPSCCs (especially tonsillar and base of tongue carcinomas) in the Nordic countries. However, beyond the adolescent and young adult birth cohorts vaccinated, there are approximately 50 birth cohorts (born in 1995 or before) that would benefit from screening for HPV-associated OPSCC. This article reviews the need, prerequisites, proof-of-concept trial and prospects of preventing HPV-associated OPSCC in the Nordic countries.

Effectiveness of the AS04-adjuvanted HPV-16/18 vaccine in reducing oropharyngeal HPV infections in young females-Results from a community-randomized trial.

We studied effectiveness of the AS04-adjuvanted HPV-16/18 (AS04-HPV-16/18) vaccine against human papillomavirus (HPV) oropharyngeal infections associated with the increase of head/neck cancers in western countries. All 38,631 resident adolescents from 1994 to 1995 birth cohorts of 33 Finnish communities were invited in this community-randomized trial (NCT00534638). During 2008-2009, 11,275 girls and 6,129 boys were enrolled in three arms of 11 communities each. In Arm A, 90% of vaccinated girls/boys, and in Arm B, 90% of vaccinated girls received AS04-HPV-16/18 vaccine. Other Arm A/B and all Arm C vaccinated participants received control vaccine. All Arm A participants and Arm B female participants were blinded to vaccine allocation. Oropharyngeal samples were analyzed from 4,871 18.5-year-old females who attended follow-up visit 3-6 years postvaccination. HPV DNA prevalence was determined by SPF-10 LiPA and Multiplex type-specific PCR. Total vaccine effectiveness (VE) was defined as relative reduction of oropharyngeal HPV prevalence in pooled Arms A/B HPV-vaccinated females vs. all Arm C females. VE against oropharyngeal HPV-16/18, HPV-31/45 and HPV-31/33/45 infections were 82.4% (95% confidence intervals [CI]: 47.3-94.1), 75.3% (95%CI: 12.7-93.0) and 69.9% (95% CI: 29.6-87.1), respectively. In conclusion, the AS04-HPV-16/18 vaccine showed effectiveness against vaccine and nonvaccine HPV-types oropharyngeal infections in adolescent females up to 6 years postvaccination.

Human Papillomavirus (HPV) Prevalence in Male Adolescents 4 Years After HPV-16/18 Vaccination.

We assessed human papillomavirus (HPV) prevalence among HPV-16/18-vaccinated and unvaccinated Finnish male adolescents participating in chlamydia screening 4 years after vaccination with AS04-adjuvanted HPV-16/18 vaccine in 2007-2009. Previously vaccinated (n = 395) or unvaccinated (n = 149) male adolescents were enrolled in 12 municipalities. First-void urine samples were tested for HPV types 6, 11, 16, 18, 31, 33, 35, 45, 51, 52, 56, 58, 59, 66, and 68, and prevalence rates for HPV-16/18, and HPV-11/16/18/31/33/45 were reduced profoundly (0% vs 2.1% [P = .02] and 0.8% vs 5.3 [P = .002], respectively). Overall HPV DNA prevalence was also significantly reduced among HPV-16/18-vaccinated (4.1%) compared with unvaccinated subjects (10.1%) (P = .01). In this post hoc study, a highly significant reduction in HPV prevalence 4 years after vaccination suggests that the bivalent HPV-16/18 vaccine has protective efficacy in men.

Neointimal coverage and vasodilator response to titanium-nitride-oxide-coated bioactive stents and everolimus-eluting stents in patients with acute coronary syndrome: insights from the BASE-ACS trial.

Incomplete stent endothelialization is associated with late and very late stent thrombosis. In a post hoc analysis of the BASE-ACS trial, we sought to assess neointimal coverage and coronary flow reserve (CFR) 9 months after implantation of titanium-nitride-oxide-coated bioactive stents (BAS) versus everolimus-eluting stents (EES) in patients with acute coronary syndrome (ACS). In the BASE-ACS trial, 827 patients with ACS were randomized to receive either BAS or EES. In the current study, we examined neointimal growth and strut coverage by optical coherence tomography and CFR by trans-thoracic echocardiography in 28 consecutive non-diabetic patients with the culprit lesion in the left anterior descending coronary artery. The primary endpoints were binary stent strut coverage and CFR at 9-month follow-up. A total of 13 patients were included in the BAS group (2,033 struts); 15 in the EES group (2,898 struts). Binary stent strut coverage was higher and malapposed struts lower with BAS versus EES (99.4 vs 89.2, and 0.2 vs 4.6%, respectively, p < 0.001 for both). Neointimal hyperplasia thickness was greater with BAS versus EES (274.2 vs 100.1 µm, respectively, p < 0.001). CFR was lower with EES versus BAS (2.2 ± 0.8 vs. 3.0 ± 0.5, respectively, p = 0.001). Abnormal CFR (<2.5) were detected in 10 patients in the EES group versus one in the BAS group (p = 0.002). The current study demonstrated that in patients with ACS, BAS resulted in improved neointimal stent strut coverage and better coronary vasodilator function as compared with EES at 9-month follow-up.

Vascular healing early after titanium-nitride-oxide-coated stent implantation assessed by optical coherence tomography.

BACKGROUND: The efficacy and safety of titanium-nitride-oxide-coated bioactive stents (BASs) were demonstrated in prior studies. In a prospective registry, we sought to explore the extent of neointimal coverage of stent struts by optical coherence tomography (OCT) at 30 days following the implantation of BASs in an unselected non-diabetic population. METHODS: We enrolled 20 consecutive nondiabetic patients who underwent BAS implantation. OCT images were obtained at 30-day follow-up. Binary stent strut coverage was defined as the number of covered struts as a percentage of all analyzed struts. RESULTS: Patients underwent OCT examination at an average of 30.5 ± 5.7 days following stent implantation. In these, 411 cross-sections were analyzed, including 3780 struts. Binary stent strut coverage was 97.2%, and the prevalence of malapposed struts was 3.2%. Mean neointimal thickness was 109.7 ± 83.6 µm. CONCLUSIONS: In the current evaluation by OCT at 30-day follow-up after BAS implantation in an unselected non-diabetic cohort, binary stent strut coverage was satisfactory and the prevalence of malapposed struts was low.

Feasibility and safety of frequency-domain optical coherence tomography for coronary artery evaluation: a single-center study.

We assessed the feasibility and safety of frequency-domain optical coherence tomography (FD-OCT) in a variety of indications. We conducted a retrospective analysis of all FD-OCT examinations performed for research and clinical indications, including stable angina, acute coronary syndromes, diagnostic procedures and percutaneous coronary intervention (PCI), at the Satakunta Central Hospital (Pori, Finland) between August 12th 2009 and February 9th 2011. All pullbacks were screened for image quality. Data on complications and clinical implications of examinations was obtained from patient records. The mean age of the patients was 65.9 ± 10.9 years (81.7% males). A total of 230 examinations were performed on 210 patients; 523 pullbacks were eventually attempted (519 successful). On average, 2.3 ± 1.1 pullbacks were performed, and 1.1 ± 0.4 vessels were scanned per examination. PCI was performed in 44.3% of examinations. Radial access was used in 70.3% of cases. Examination was successful in 202 (87.8%) examinations. One patient died of heart failure later after PCI for acute myocardial infarction. No cases of major bleeding, myocardial infarction, contrast-induced nephropathy, or pericardial tamponade were encountered. Chest pain occurred in 10.9% of examinations, minor bleeding in 4.8%, and myocardial ischemia in 2.6%. Femoral access was associated with fewer blood and decentration artefacts and a trend towards better image quality when compared to radial access, with no difference in complications. After the first 50 examinations, there appeared to be fewer artefacts in the subsequent examinations. The current study demonstrated that FD-OCT is feasible, with infrequent complications.

Early vascular healing after endothelial progenitor cell capturing stent implantation.

OBJECTIVES: To assess early vascular healing with endothelial progenitor cell (EPC)-capturing stents. BACKGROUND: Endothelialization of stent struts is crucial after stenting, since delayed vascular healing predisposes to stent thrombosis. The antibody-coated Genous stent promotes rapid endothelialization by capturing circulating EPCs. METHODS: We enrolled 20 patients who had EPC-capturing stent implanted in the left anterior descending (LAD) coronary artery. Patients underwent optical coherence tomography 30 days following the index procedure. Coronary flow reserve (CFR) was assessed in the LAD by transthoracic echocardiography at 30 days. RESULTS: After follow-up of 31.8 ± 5.3 days, the binary stent strut coverage was 95% and the percentage of malapposed struts was 2.4%. No thrombi were detected. The mean neointimal hyperplasia (NIH) thickness was 108 ± 96 µm and the percent NIH area was 8.9 ± 7.4%. The mean CFR was 2.4 ± 0.7. CONCLUSIONS: The EPC-capturing stent showed rapid endothelialization, low NIH area, and few malapposed struts at 30 days.

Stent strut coverage of titanium-nitride-oxide coated stent compared to paclitaxel-eluting stent in acute myocardial infarction: TITAX-OCT study.

Drug-eluting stents (DES) have reduced the rate of restenosis but recent studies have raised concern over the risk of late stent thrombosis (LST). Incomplete stent endothelialization and delayed vascular healing have been associated with LST. The titanium-nitride-oxide coated bio-active stent (BAS) has shown promising results in patients with acute coronary syndromes, but there is little long-term optical coherence tomography (OCT) data comparing BAS with DES. The TITAX-AMI trial is a prospective, randomized, multicenter trial comparing BAS to paclitaxel-eluting stent (PES) in 425 patients with acute myocardial infarction. A total of 18 patients (9 per group) with no major cardiac events during follow-up, were enrolled in this substudy >36 months (mean 47 months) after stent implantation. Quantitative coronary angiography was performed and stent strut endothelialization and vascular healing were assessed with OCT. The binary stent strut coverage was significantly higher in the BAS group compared with the PES group (99.6 vs. 89.2%, p < 0.001) and there were less malapposed struts in the BAS group (0.2 vs. 13.8%, respectively, p < 0.001). The neointimal hyperplasia (NIH) thickness (266 ± 166 vs. 126 µm ± 126 µm, p < 0.001) and percentage of NIH area (26.2 vs. 7.6%, p < 0.001) were greater in the BAS group than in the PES group. Late incomplete endothelialization was not uncommon after PES implantation. Stents in the BAS group were completely endothelialized. This difference may contribute to the more common LST after PES implantation in the TITAX-AMI trial.