Risk of CIN2+ following a diagnosis of genital warts: a nationwide cohort study.

OBJECTIVES: Individuals with genital warts may be particularly susceptible to human papillomavirus since they have failed to clear the virus. Consequently, women with genital warts could be at increased risk of cervical dysplasia. In this cohort study we aimed to compare the incidence of cervical intraepithelial neoplasia grade 2 or worse (CIN2+) in women with a diagnosis of genital warts with that of the general female population without genital warts. METHODS: Using the Danish nationwide population-based health data registers, we identified women between 15 and 45 years and followed them for diagnoses of CIN2+ from 1995 to 2006. Genital wart diagnoses were recorded from birth, and Cox regression with attained age as underlying scale was used to estimate age-dependent HRs for the risk of CIN2+ with genital warts as a time-varying exposure. RESULTS: Among 918 609 women without genital warts and 32 218 women with genital warts, 30 209 and 1533 women, respectively, had a subsequent diagnosis of CIN2+. A significantly higher risk of CIN2+ was found among women with genital warts relative to those without (HR, 2.43; 95% CI 2.30 to 2.56). Treatment-resistant genital warts posed a significantly higher risk of CIN2+ than did transient genital warts (HR, 1.20; 95% CI 1.01 to 1.43). The risks remained elevated more than 4 years after the genital wart diagnosis. CONCLUSION: Clinicians should ensure that women with genital warts are screened for cervical cancer after the genital wart diagnosis and that they continue to be screened on time.

Significant Reduction in the Incidence of Genital Warts in Young Men 5 Years into the Danish Human Papillomavirus Vaccination Program for Girls and Women.

BACKGROUND: Denmark introduced the quadrivalent human papillomavirus vaccine into the vaccination program for 12- to 15-year-old girls in 2008 to 2009. In 2012, the program was supplemented with a catch-up program for women aged up to 27 years. We evaluated the effectiveness of the Danish vaccination program on the nationwide incidence of genital warts (GWs), after the second catch-up by including information on both hospital treatments and on self-administered treatment with podophyllotoxin. Genital wart incidence was investigated in both sexes; however, the main focus was on potential herd protection of men. METHODS: Incident cases of GWs were identified from the Danish National Patient Register and through redemptions of prescription for podophyllotoxin in the Danish National Prescription Registry in 2006 to 2013. Age-specific incidence rates (IRs) were assessed, and estimated annual percentage change (EAPC) was calculated by Poisson regression. RESULTS: Genital wart incidence was either stable or increased in both sexes in 2006 to 2008. After introduction of the vaccination program, GW incidence decreased significantly in women aged 12 to 35 years and men aged 12 to 29 years, with rapid decrease among 16- to 17-year-olds (IRwomen, from 1071 to 58 per 100,000 person-years [EAPC, -55.1%; 95% confidence interval, -58.7 to-51.2]; IRmen, from 365 to 77 per 100,000 person-years [EAPC, -36.6%; 95% confidence interval, -40.5 to -32.5] in 2008-2013). CONCLUSIONS: We found a significantly decreasing incidence of GWs in women up to 35 years of age after the start of the human papillomavirus vaccination program. A similar pattern was observed for men aged 12 to 29 years, indicating substantial herd protection.

Dose-Related Differences in Effectiveness of Human Papillomavirus Vaccination Against Genital Warts: A Nationwide Study of 550,000 Young Girls.

BACKGROUND: Reducing the number of doses in the human papillomavirus (HPV) vaccination regimen from 3 to 2 could increase coverage rates. In this cohort study, we assessed the risk of genital warts (GWs) according to timing and number of doses of quadrivalent HPV vaccine. METHODS: From population-based registries, we identified all girls in Denmark born during 1985-1999, for whom information on HPV vaccinations was retrieved. The cohort was followed for GW occurrence during 2006-2012. Incidence rate ratios (IRRs) were calculated by Poisson regression to determine differences in GW rates by number of vaccine doses. RESULTS: Of the 550,690 girls in the cohort, 361 734 had been vaccinated. Of these, 25.9% had been vaccinated twice and 58.8% 3 times. The risk of GWs decreased significantly with each additional dose of vaccine. For girls who received 2 doses, extension of the interval between doses reduced the incidence of GWs. In comparison with a 2-month interval, the incidence of GWs was reduced by 45% (95% confidence interval [CI], 20%-62%), 55% (95% CI, 35%-69%), and 63% (95% CI, 44%-75%), with an interval of 4, 5, and 6 months, respectively. The IRR of 2 vs 3 doses was close to 1, with an interval of about 6 months between the first 2 doses. CONCLUSIONS: With the original vaccine schedule, completion of 3 doses seems to be required to obtain full protection against GWs. A 2-dose regimen may be as effective if the dosing interval is extended to around 6 months, although the long-term effectiveness of this regimen is unknown.

Low prevalence of oral and nasal human papillomavirus in employees performing CO2-laser evaporation of genital warts or loop electrode excision procedure of cervical dysplasia.

Risk of human papillomavirus (HPV) transmission during laser vaporisation of genital warts or loop electrode excision procedure is controversial. An oral rinse, a nasal swabs, history of HPV related diseases and data on HPV exposure were collected from 287 employees at departments of dermato-venerology and gynaecology in Denmark. A mucosal HPV type was found among 5.8% of employees with experience of laser treatment of genital warts as compared to 1.7% of those with no experience (p = 0.12). HPV prevalence was not higher in employees participating in electrosurgical treatment or cryotherapy of genital warts, or loop electrode excision procedure compared with those who did not. HPV 6 or 11 were not detected in any samples. Hand warts after the age of 24 years was more common among dermatology than among non-dermatology personnel (18% vs. 8.0%, p = 0.03). Mucosal HPV types are infrequent in the oral and nasal cavity of health care personnel, however, employees at departments of dermato-venereology are at risk of acquiring hand warts.

Strongly decreased risk of genital warts after vaccination against human papillomavirus: nationwide follow-up of vaccinated and unvaccinated girls in Denmark.

BACKGROUND: A reduction in the incidence of genital warts (GWs) is one of the first markers of the effectiveness of vaccination against human papillomavirus (HPV) at the population level. The aim of this cohort study was to use individual information on HPV vaccination status to assess the effect on risk of GWs. METHODS: Population-based registries were used to identify all girls in the birth cohorts 1989-1999 in Denmark, and information about HPV vaccination was obtained for the period 2006-2012. The cohort was linked to incident cases of GWs, and vaccinated and unvaccinated girls were compared using Cox proportional hazards models. RESULTS: A total of 248 403 girls were vaccinated. The relative risk of GWs among girls who had received at least 1 dose of vaccine compared with unvaccinated girls was 0.12, 0.22, 0.25, and 0.62 for those born in 1995-1996, 1993-1994, 1991-1992, and 1989-1990, respectively (P for trend < .0001). No GWs occurred among vaccinated girls in the youngest birth cohort (1997-1999). CONCLUSIONS: The strong, highly significant reduction in the occurrence of GWs among vaccinated girls indicates an early and marked population effect of the national HPV vaccination program and may forecast a similar effect on cervical precancerous lesions.

Significant decrease in the incidence of genital warts in young Danish women after implementation of a national human papillomavirus vaccination program.

BACKGROUND: Approximately 90% of genital warts (GWs) are caused by human papillomavirus (HPV) types 6 and 11. Denmark has provided the quadrivalent HPV vaccine to all 12-year-old girls since 2009 and catch-up vaccination to girls up to 15 years since 2008, with up to 80% to 85% vaccine coverage. We determined the incidence of GWs in Denmark since 1996, focusing on the period after licensing of HPV vaccination (October 2006). METHODS: From the Danish National Patient Register, we identified all hospitalizations and outpatient consultations for GWs between January 1995 and July 2011. Poisson regression was used to estimate average annual percentage changes. RESULTS: The overall incidence of GWs in women increased significantly until 2007, followed by an average yearly decline of 3.1% (95% confidence interval [CI], -5.5 to -0.7). In men, the incidence increased by 6.2% per year from 2004 (95% CI, 4.6-7.8). Stratifying on age, a significant decline was seen only for young women, particularly those aged 16 to 17 years, in whom GWs were virtually eliminated (average annual percentage change, -45.3%; 95% CI, -55.8 to -33.3). The incidences of genital Chlamydia, syphilis, and gonorrhea were stable or increased during the study period. CONCLUSIONS: The incidence of GWs decreased substantially among women with high HPV vaccine coverage, pointing to the effect of the national HPV vaccination program.

Genital warts and risk of cancer: a Danish study of nearly 50 000 patients with genital warts.

BACKGROUND: We conducted a large national cohort study to examine the risk of cancer among men and women with genital warts (GW). METHODS: By use of the Danish National Patient Register, we identified 16,155 men and 32,933 women who received a diagnosis of GW during 1978-2008. Standardized incidence ratios (SIRs) were computed as estimates of the relative risk of specific cancers or sites. RESULTS: A diagnosis of GW was strongly related to anal (SIR for men, 21.5; SIR for women, 7.8), vulvar (SIR, 14.8), vaginal (SIR, 5.9), cervical (SIR, 1.5), penile (SIR, 8.2), and head and neck cancer (SIR, 2.8), including subsites of head and neck cancer with confirmed HPV association (SIR for men, 3.5; SIR for women, 4.8). The risks remained elevated for >10 years following GW diagnosis. In addition, we found moderately increased SIR estimates for nonmelanoma skin cancer, smoking-related cancers, and Hodgkin and non-Hodgkin lymphoma. CONCLUSIONS: Individuals with GW have a long-term increased risk of anogenital cancers and head and neck cancers. The elevated risks of nonmelanoma skin cancers might indicate an association with HPV, while excess risks of other cancers could point to differences in other risk factors between individuals with GW and the general population.

Trends in head and neck cancer incidence in Denmark, 1978-2007: focus on human papillomavirus associated sites.

The aim of our study was to assess the overall trends in the incidence of head-and-neck cancer (HNC) among Danish men and women in 1978-2007, to describe the distribution and incidences of HNCs at different anatomical sites, and to determine whether the incidence of human papillomavirus (HPV)-associated cancers is increasing. Data were extracted from the nationwide Cancer Registry database. To assess the possible impact of HPV infection, the sites of squamous cell carcinomas were categorized as HPV-associated, potentially HPV-associated or HPV-unrelated. In total, 26,474 incident cases were identified and the overall incidence increased throughout the period. Significantly increasing incidence rates were notably seen for tumors in the oral cavity (2.2% per year), tonsils (4.8% per year), oropharynx (3.5% per year) and hypopharynx (4.4% per year). A significantly decreasing incidence of lip cancer was observed among men (-5.0% per year). Cancers at HPV-associated sites (n = 3650) showed strongly increasing incidence rates, primarily in individuals < 60 years. In contrast, HNCs at sites not related to HPV infection showed a significant decrease (in men) or virtually no change in incidence (in women). Our results suggest a marked impact of HPV infection on the epidemiology of HNCs in Denmark. HPV16 is the type most often found in HNCs; thus, the recent introduction of vaccination against HPV may in the future prevent HPV-associated cancers of the head and neck.

[Treatment of patients with oral squamous cell carcinomas (T1-T2N0M0). Initial experiences with national guidelines]. / Behandling af patienter med orale planocellulaere karcinomer. De første erfaringer med nationale retningslinjer.

INTRODUCTION: In 2003 the national guidelines for the treatment of patients with oral squamous cell carcinomas (OSCC) were established. Patients with clinically negative neck are now treated with surgery as opposed to radiotherapy previously. The aim of this study is to evaluate the surgical morbidity for these patients. MATERIALS AND METHODS: This study included patients with primary diagnosed OSCC classified as T1-T2N0M0 treated between June 2003 and June 2005 at the Department of Otolaryngology--Head & Neck Surgery, Copenhagen University Hospital. The patients had their charts reviewed and 30 went to a clinical examination and were interviewed about complaints following the surgical treatment. RESULTS: 60 patients were included. In order to be able to determine the complications of the surgical treatment, 30 of the 60 patients were excluded from the clinical examination. All patients attended and the median follow-up was 9 months. The transient complication most frequently registered was postoperative bleeding. The most frequent permanent complications were damage of the marginal branch (10%) and the sensory nerves, the major auricular nerve and the lingual nerve (13%). Patients undergoing bilateral neck dissection have an increased risk of complications. CONCLUSION: The majority of complications were transient, and the patients had few complaints after the operation. The most frequently encountered complication was nerve damage, but the general morbidity was estimated to be reasonable. It is important that the guidelines are followed consistently and that the surgical skills are evaluated.