Jon Mork

Human papillomavirus infection as a risk factor for squamous-cell carcinoma of the head and neck

BACKGROUND Oncogenic human papillomaviruses (HPVs), especially HPV type 16 (HPV-16), cause anogenital epithelial cancers and are suspected of causing epithelial cancers of the head and neck. METHODS To examine the relation between head and neck cancers and HPVs, we performed a nested case-control study within a joint Nordic cohort in which serum samples were collected from almost 900,000 subjects. Samples collected at enrollment from 292 persons in whom squamous-cell carcinoma of the head and neck developed, on average, 9.4 years after enrollment and from 1568 matched controls were analyzed for antibodies against HPV-16, HPV-18, HPV-33, and HPV-73 and for cotinine levels as a marker of smoking habits. Polymerase-chain-reaction (PCR) analyses for HPV DNA were performed in tumor tissue from 160 of the study patients with cancer. RESULTS After adjustment for cotinine levels, the odds ratio for squamous-cell carcinoma of the head and neck in subjects who were seropositive for HPV-16 was 2.2 (95 percent confidence interval, 1.4 to 3.4). No increased risk was observed for other HPV types. Fifty percent of oropharyngeal and 14 percent of tongue cancers contained HPV-16 DNA, according to PCR analysis. CONCLUSIONS HPV-16 infection may be a risk factor for squamous-cell carcinoma of the head and neck.

Human papillomavirus infection as a risk factor for anal and perianal skin cancer in a prospective study

Human papillomavirus has emerged as the leading infectious cause of cervical and other anogenital cancers. We have studied the relation between human papillomavirus infection and the subsequent risk of anal and perianal skin cancer. A case–cohort study within two large Nordic serum banks to which about 760 000 individuals had donated serum samples was performed. Subjects who developed anal and perianal skin cancer during follow up (median time of 10 years) were identified by registry linkage with the nationwide cancer registries in Finland and Norway. Twenty-eight cases and 1500 controls were analysed for the presence of IgG antibodies to HPV 16, 18, 33 or 73, and odds ratios of developing anal and perianal skin cancer were calculated. There was an increased risk of developing anal and perianal skin cancer among subjects seropositive for HPV 16 (OR=3.0; 95%CI=1.1–8.2) and HPV 18 (OR=4.4; 95%CI=1.1–17). The highest risks were seen for HPV 16 seropositive patients above the age of 45 years at serum sampling and for patients with a lag time of less than 10 years. This study provides prospective epidemiological evidence of an association between infection with HPV 16 and 18 and anal and perianal skin cancer.Human papillomavirus has emerged as the leading infectious cause of cervical and other anogenital cancers. We have studied the relation between human papillomavirus infection and the subsequent risk of anal and perianal skin cancer. A case–cohort study within two large Nordic serum banks to which about 760 000 individuals had donated serum samples was performed. Subjects who developed anal and perianal skin cancer during follow up (median time of 10 years) were identified by registry linkage with the nationwide cancer registries in Finland and Norway. Twenty-eight cases and 1500 controls were analysed for the presence of IgG antibodies to HPV 16, 18, 33 or 73, and odds ratios of developing anal and perianal skin cancer were calculated. There was an increased risk of developing anal and perianal skin cancer among subjects seropositive for HPV 16 (OR=3.0; 95%CI=1.1–8.2) and HPV 18 (OR=4.4; 95%CI=1.1–17). The highest risks were seen for HPV 16 seropositive patients above the age of 45 years at serum sampling and for patients with a lag time of less than 10 years. This study provides prospective epidemiological evidence of an association between infection with HPV 16 and 18 and anal and perianal skin cancer.

Familial risk in head and neck squamous cell carcinoma diagnosed before the age of 45: a population-based study.

This population-based study analyses familial risk as a factor in the development of head and neck squamous cell carcinoma before the age of 45. Two different designs were used: (1) estimation of standardised incidence ratios (SIRs) for cancer among first-degree relatives of 127 young head and neck cancer probands; and (2) estimation of odds ratios (ORs) for developing head and neck cancer associated with cancer in a first-degree relative. SIRs of cancer of the respiratory and upper digestive tract (lungs, oesophagus, and smoking-related head and neck sites [RUDT]) for first-degree relatives were 4.3 (95% confidence intervals or 95% CI of 1.6-9.5) for female patients, 1.0 (95% CI = 0.3-2.6) for male patients and 1.9 (95% CI = 0.9-3.5) for both sexes combined. ORs for head and neck cancer before the age of 45, in association with cancer of RUDT in a first-degree relative were 5.0 (95% CI = 1.4-17.3) for women, 1.1 (95% CI = 0.3-3.3) for men, and 2.0 (95% CI = 0.9-4.4) for both sexes combined. Hence, when analysing both sexes combined, our familial risk estimates for head and neck cancer showed non-significant increases. An explanation for the unexpected sex asymmetry in familial risk could be an interaction between inherent cancer susceptibility and a female biological characteristic. Alternatively, it could be artefacts caused by differences in familial smoking habits.

SQUAMOUS CELL CARCINOMAS OF THE HEAD AND NECK IN NORWAY, 1953-92 : AN EPIDEMIOLOGIC STUDY OF A LOW-RISK POPULATION

Trends in incidence, five-year relative survival, and mortality among patients in Norway with squamous cell carcinoma of the oral sites, oro-/hypopharynx, and larynx were studied for the period 1953-92. Throughout the first part of the study period, age-adjusted incidence rates (AAIR) of oral cancer remained stable in both genders. Since the end of the 1960s, AAIRs increased by 13 percent per five-year period in males and 12 percent in females. The figures suggest increased male incidence rates of oral cancer in younger age groups. During the same period, AAIRs of cancers of the oro-/hypopharynx in males increased by 19 percent per five-year period. The AAIRs of laryngeal cancer increased steadily from 1953-92 among both males and females by 17 percent and 21 percent per five-year period, respectively. For all sites, changes in AAIRs for males were greater in rural than in urban areas. No improvement in detection of disease at a localized stage was observed for either gender. There are indications of improvements in the five-year relative survival rates for oral and pharyngeal cancer in both genders. For all sites, relative survival was better in younger than in older patients. Only in the case of pharyngeal cancer in males was an increase in disease-specific mortality rates positive for a time trend.

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.

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.