Human papillomavirus in oropharyngeal squamous cell carcinoma in South-Eastern Norway: prevalence, genotype, and survival.

The objectives of this study were to assess the prevalence of high-risk human papillomavirus (HR HPV) and survival in all oropharyngeal cancer (OPSCC) patients in a Norwegian population cohort in 2010-2011. Clinical data were retrieved from hospital records. Biopsies from 166 patients were tested for the presence of HR HPV by qualitative polymerase chain reaction (qPCR). p16 immunohistochemistry was performed in 138 cases. Survival was compared between groups of patients with tumors positive for HPV16 and other HR HPV genotypes, and patients with HPV negative tumors. HR HPV was detected in 127 out of 166 cases (77%). HPV16 was the most prevalent genotype (n = 108), followed by HPV33 (n = 12), HPV18 (n = 3), and HPV31/35/56/59 (n = 1). There was a robust and significant association between p16 and HR HPV status. (Chi square 70.8; p < 0.0001). Among p16-positive/HR HPV-positive cases, the distribution of HPV16 and other HR HPV types was not significantly different [91% (88/97) versus 82% (14/17); p = 0.30]. HR HPV-negative patients had reduced overall survival compared to HR HPV-positive patients [hazard ratio 0.30; 95% confidence interval (CI) 0.16-0.56, p < 0.001]. Non-HPV16 HR HPV-positive patients had significantly poorer overall survival than HPV16-positive patients (hazard ratio 0.35; 95% CI 0.14-0.85, p = 0.02). Prevalence of HR HPV in OPSCC in Norway is high, and similar to the level reported in recent years from other countries in Northern Europe and in North America. HPV genotyping may be valuable in future risk-stratification algorithms for treatment of patients with HPV-positive OPSCC.

Pre-diagnostic dynamic HPV16 IgG seropositivity and risk of oropharyngeal cancer.

OBJECTIVE: The aim of this study was to determine the association of HPV16 antibodies (Abs) and oropharyngeal cancer (OPC) risk in sera obtained prior to clinical diagnosis. METHODS: We identified 92 participants with incident OPC and 460 matched controls from the Janus Serum Bank Cohort in Norway. Archived tumor specimens were requested for a subset of the cases. Serum samples were collected from cases, on average, 9.3years before diagnosis (range, 0.1-14.9years). Ten cases had serum samples from multiple time points. IgG seropositivity to 8 HPV16 antigens was determined, and a logistic regression classifier of a panel of all early-antigen (EA) Abs for the predictive diagnosis of OPC was applied. RESULTS: HPV16 EA seropositivity was present in 25.0% of patients with OPC and 7.6% of controls (odds ratio (OR), 4.1; 95% CI, 2.3-7.2, p<0.0001). Abs to E2 were strongly associated with cases 0-2years pre- diagnosis (OR, 150.1; 95% CI, 27.4-1040.0, p<0.0001), and the probability of seropositivity was inversely associated with time to diagnosis (OR, 0.7 per additional year; 95% CI, 0.6-0.9, p=0.0002). Abs to E2 were also strongly associated with tumor HPV status (OR, 35.6; 95% CI, 8.7-200.0, p<0.0001). A positive score on the binary classifier was associated with an overall OR of 15.8 (95% CI, 5.6-53.4) compared with controls (p<0.05), and was strongly associated with tumor HPV status (OR, 27.4; 95% CI, 8.6-99.6, p<0.001). CONCLUSIONS: HPV16 Abs are detectable years prior to diagnosis of OPC, and the probability of seropositivity increases closer to diagnosis.

Population-based evidence of increased survival in human papillomavirus-related head and neck cancer.

BACKGROUND: Evidence from clinical, population-based and molecular studies has shown that human papillomavirus (HPV) infection can be a causal risk factor for a subset of head and neck squamous cell carcinomas (HNSCC). It is proposed that HPV-associated oropharyngeal cancer is a new disease entity that requires treatment and prevention strategies distinct from present recommendations. METHODS: In our population-based study we estimated incidence and survival trends in 8270 patients with HPV-related HNSCC (HPV(+)HNSCC) and HPV-unrelated HNSCC (HPV(-)HNSCC) in Norway over the past three decades. RESULTS: In the period 1981-1995, patients with HPV(+)HNSCC had poorer survival than HPV(-)HNSCC (adjusted hazard ratio (HR) 1.3, 95% confidence interval (CI): 1.14-1.44). By 1996-2007, survival had increased in both groups, but the increase was significantly greater among HPV(+)HNSCC patients (HR 0.57, 95% CI: 0.48-0.67). During the same period, incidence also increased, but only for HPV(+)HNSCCs. From 1981-1995 to 1996-2007, median age at diagnosis for HPV(+)HNSCC decreased from 63.2 to 59.8 years, while for HPV(-)HNSCC median age at diagnosis of 66.6 years remained unchanged. CONCLUSIONS: We demonstrate a population level improvement in survival among patients with oropharyngeal squamous cell cancers commonly related to infection with HPV. In contrast, patients with HNSCC not related to HPV only showed a modest improvement in survival in the period 1981-2007. A concomitant increase in incidence and survival was observed for HPV-related cancers only. This trend cannot be explained by changes in treatment, cancer registration nor screening, but is most likely due to an increased prevalence of HPV-positive tumours.

Time trends in pharyngeal cancer incidence in Norway 1981-2005: a subsite analysis based on a reabstraction and recoding of registered cases.

OBJECTIVE: Incidence rates of oropharyngeal squamous cell carcinoma (SCC) have been reported to be increasing in several countries in recent decades, contrasting with trends of SCCs diagnosed in neighboring anatomical sites. We investigated whether changes in classification systems and/or coding/registration practices might explain the trends in Norway, focusing on changes in oropharyngeal cancer. METHODS: Trends in cancers of the oropharynx, base of tongue, nasopharynx, hypopharynx were graphically presented for the period 1981-2005, before and after recoding. Age-period-cohort and future prediction models were fitted to oropharyngeal SCC incidence. RESULTS: A total of 85 (3.7%) of the 2315 pharyngeal cancers required recoding. Rates of oropharyngeal cancer in Norway were consistently two to three times higher in men, with rapid increases in both men (5% per annum) and women (4.2% per annum). Assuming generational effects, male cohorts born 1915-1950 were at increasingly higher risk of the disease. The number of oropharyngeal cancer cases is expected to double in Norway by 2020. CONCLUSIONS: The trends were not considered materially biased by potential artefacts. The increasingly higher proportion of oropharyngeal SCC cancers is more likely explained by other factors, including an increasing high-risk HPV prevalence among recent cohorts. These results will likely have consequences on treatment and health care provision in the near future.

Multimodal treatment of osteogenic sarcoma of the jaw.

Osteosarcomas (OSs) account for 40 to 60% of primary malignant bone tumors. About 10% occur in the head and neck region, frequently in the mandibula or maxilla. We treated a 30-year-old patient with 26-month history of right-sided facial pain and paresthesia. Investigation showed high-grade OS of the right mandibular coronoid process, affecting the mandibular nerve, middle cranial fossa, internal jugular vein, and internal carotid artery (ICA). True en bloc resection was performed after upfront adjuvant chemotherapy. The ICA was trap-ligated intradurally, whereafter the floor of the middle fossa, including the mandibular nerve and the glenoid fossa, was detached from the skull base in one piece. Subsequently, a hemimandibulectomy, total parotidectomy, ICA sacrifice, and removal of the pterygoid plates and muscles were performed, and the abovementioned structures were removed as a solitary specimen, including the facial nerve branches overlying the tumor. A sural nerve graft was interposed between five major facial nerve branches to reanimate the face. The patient had an uneventful recovery, is able to eat, and has a partial facial nerve palsy. He has no tumor recurrence 26 months after surgery. OS of the jaw should be treated with radical surgery as the primary modality.

Incidence and survival of squamous cell carcinoma of the tongue in Scandinavia, with special reference to young adults.

In several countries, increased incidence of squamous cell carcinoma (SCC) of the tongue in young adults has been suspected during the last decades. Some reports indicate a lower survival rate for young patients compared to older patients. In other reports, there has not been any considerable difference in survival when comparing young adults to older patients, whereas some authors have shown better survival for young adults. This disease is rare in young adults, and early reports were based on comparable small numbers and selected patients. Our aim was first to perform a population-based study to determine if an increased incidence in SCC of the tongue could be verified in a larger population comprising the Scandinavian countries Denmark, Finland, Sweden and Norway. A second aim was to determine survival rates for young adults compared to older patients. The material was based on the annual cancer incidence and survival reports from the Scandinavian cancer registries. The study period was 1960-1994. During that period, 5,024 SCCs of the tongue were reported. Of these, 276 (5.5%) were young adults (20-39 years). The incidence increased at all ages except for women 65-79 years old. The increase was most pronounced in young adults: 0.06-0.32 for men and 0.03-0.19 for women, counted by 100,000 person-years. Relative survival was significantly better for young adults compared to older patients.