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Objective: To evaluate the clinical course of juvenile-onset recurrent respiratory papillomatosis (RP) with respect to age, disease duration, and maternal condylomas., Design: Inception cohort study., Setting: All ear, nose, and throat departments in public Danish hospitals., Patients: Fifty-seven Danish children diagnosed with RP and born between 1974 and 1993 were observed for an average of 14 years after diagnosis., Main Outcome Measure: Removal of respiratory papillomas by knife biopsy, laser surgery, or cryotherapy., Results: Children younger than 5 years diagnosed with RP underwent an average of 4.1 surgeries in the first year of disease, the highest rate among all our patients. The overall surgery rate decreased over time after initial diagnosis but remained significantly higher for children with a younger age of onset for the first 4 years of disease (P <.001) and for children with a maternal history of condylomas in pregnancy for years 4 to 10 of the disease (P <.001). We also observed an independent and statistically significant (P <.001) decreasing surgery rate with increasing age and time from initial diagnosis. The trend for children with recurrent disease was a decreasing rate of surgical procedures (28 of 42 patients with recurrent disease); however, a third of patients (14/42) demonstrated a constant or increasing rate of surgical procedures over time., Conclusions: The clinical course of RP is characterized by a high frequency of surgeries soon after diagnosis that diminishes over time and with increasing age. Additional studies are warranted to identify factors associated with cases that do not conform to the usual disease course.

Objective: To assess the risk of juvenile-onset recurrent respiratory papillomatosis conferred by a maternal history of genital warts in pregnancy, and to identify additional cofactors such as the method of delivery (cesarean versus vaginal) and procedures or complications during pregnancy., Methods: A retrospective cohort design was used to evaluate maternal and infant characteristics associated with respiratory papillomatosis among Danish births between 1974 and 1993. Using data from Danish registries, we identified 3033 births with a maternal history of genital warts during pregnancy. Fifty-seven respiratory papillomatosis cases were identified by review of medical records from ear, nose, and throat departments., Results: Seven of every 1000 births with a maternal history of genital warts resulted in disease in the offspring, corresponding to a 231.4 (95% confidence interval 135.3, 395.9) times higher risk of disease relative to births without a maternal history of genital warts. In women with genital warts, delivery times of more than 10 hours were associated with a two-fold greater risk of disease. Cesarean delivery was not found to be protective against respiratory papillomatosis, and no other procedures or complications during pregnancy were observed to increase the risk of respiratory papillomatosis., Conclusion: A maternal history of genital warts in pregnancy is the strongest risk factor for respiratory papillomatosis in the child. Future studies should examine the efficacy of genital wart treatment for the prevention of disease.

Objectives: To determine a putative role and relation between human papilloma virus (HPV) and p53 in the etiology of sinonasal carcinomas associated with papillomas., Study Design: The study group consists of all patients with sinonasal carcinomas associated with papillomas diagnosed in Denmark from 1980 to 1998. After reviewing our national pathological files, tumor tissues from 36 patients were collected, comprising 15% of the total cases of sinonasal carcinomas. In 35 cases a squamous cell carcinoma was demonstrated and in one case an adenocarcinoma was evident. Inverted papilloma was associated with carcinoma in 31 cases and exophytic papillomas in 5 cases. The material was investigated for HPV using polymerase chain reaction analyses with two sets of consensus primers (GP5+/GP6+ and MY09/MY11). The HPV-positive cases were submitted to dot-blot hybridization to establish the HPV type. Using immunohistochemistry, the p53 expression was determined. A p53 overexpression is defined as positive staining in 10% or more of the tumor cells., Results: Among 30 examined cases of carcinomas associated with inverted papillomas, 4 cases were HPV-positive (13%). P53 overexpression was not shown among the HPV-positive cases, whereas p53 overexpression was seen in 21 of the 24 (88%) examined HPV-negative cases. Among the 5 carcinomas associated with exophytic papillomas, HPV was demonstrated together with p53 overexpression in 3 cases (60%). In addition, one case more was with p53 overexpression., Conclusion: An inverse relation between HPV and p53 overexpression in sinonasal carcinomas associated with inverted papillomas appears to have been demonstrated. HPV and p53 might also have an etiological role among the carcinomas associated with exophytic papillomas.

The incidence rate of laryngeal papillomas in a Danish subpopulation (approximately 2.8 million inhabitants) was 3.84 x 10(-6) per year in the period 1968-1984. For juvenile papillomas the incidence rate was 3.62 x 10(-6), compared with 3.94 x 10(-6) for laryngeal papillomas of adult onset. When comparing different time periods a significantly low incidence was found in the time 1965-1968, while the incidence remained constant in 1969-1984. The low incidence rate in the early period may be real, but selectional bias may have played a part. It is general anticipated that maternal genital HPV-infections may serve as an HPV-reservoir, and that juvenile laryngeal papillomas is a result of HPV transmission from the mother to the child during birth. In the period in question cervical HPV-infections have been recorded with increasing frequency in younger women, indicating that the prevalence is rising. However, this is not reflected in the incidence of laryngeal papillomas.