Factors associated with a cervical high-grade lesion on cytology or a positive visual inspection with acetic acid among more than 3300 Tanzanian women.

OBJECTIVES: Cervical cancer screening by visual inspection with acetic acid (VIA) is a widely used alternative to cytology in developing countries. This study aimed to evaluate risk factors associated with a positive VIA test and with cervical high-grade lesions on cytology. METHODS: We conducted a large cross-sectional study among 3339 women from urban and rural Tanzania. Study participants were interviewed about socio-demographic, reproductive and lifestyle factors. Blood samples were tested for HIV, and a gynaecological examination was performed. Human papillomavirus (HPV) status was determined by Hybrid Capture 2, and HPV genotyping was done using the LiPA Extra test. We used multivariable logistic regression to estimate adjusted odds ratios (ORs) and confidence intervals (CIs). RESULTS: The strongest risk factors for VIA positivity were positivity to HIV (OR = 3.48; 95% CI: 2.34-5.17) or to high-risk HPV (HrHPV) (OR = 1.97; 95% CI: 1.37-2.85). HrHPV was by far the strongest predictor of high-grade cytology (OR = 110.1; 95% CI: 50.4-240.4), while there was no significant association with HIV in the multivariable analysis (OR = 1.27; 95% CI: 0.78-2.08). After adjustment for HrHPV, HIV and age, the risk of high-grade cytology also increased with increasing age, number of births and low body mass index (BMI), while high BMI decreased the risk of VIA positivity. CONCLUSIONS: Infection with HrHPV is a major risk factor for high-grade cytology, while VIA positivity is associated with HIV and to a lesser extent with HrHPV.

Effectiveness of varying number of doses and timing between doses of quadrivalent HPV vaccine against severe cervical lesions.

BACKGROUND: Based on immunogenicity studies, a 2 dose HPV vaccination-schedule was recently recommended for girls younger than 15 years. We aimed to investigate the effectiveness of quadrivalent HPV (qHPV) vaccination against CIN2 or worse (CIN2+), by age at vaccination, number of doses, and to test whether optimal timing of 2 doses of qHPV vaccine can confer the same level of protection as the originally recommended three dose-schedule. METHODS: A population-based cohort of all women aged 13-30 years, living in Denmark or Sweden during 2006-2013, was followed for qHPV vaccination status and first occurrence of CIN2+. RESULTS: The study cohort comprised 2,253,561 women, of which 33% were vaccinated during follow-up, and 1.7% were diagnosed with CIN2+. Vaccination at ages 13-16 and 17-19 was associated with a reduced risk of CIN2+ after 3 doses (IRR = 0.23, 95% CI 0.11-0.49, and IRR = 0.65, 95% CI 0.41-1.03, respectively), compared to being unvaccinated. After 1 and 2 doses there was a reduced risk, but not statistically significant. Women vaccinated ages 13-16 with 2 doses, where time between first and second dose was 5 months or longer showed no difference in risk compared to 3 doses. CONCLUSIONS: Women vaccinated with 3 doses of qHPV showed a reduced risk of CIN2+ if they were vaccinated before age 20, with a further reduced risk if vaccinated before age 17. Vaccination with 2 doses, with the second dose 5 months or longer after the first dose, did not yield an increased risk of CIN2+, compared to 3 doses.

Socioeconomic predictors of human papillomavirus vaccination in Danish men - A nationwide study.

BACKGROUND: The quadrivalent human papillomavirus vaccine was licensed in Denmark in 2006. Unlike women, men are not offered human papillomavirus vaccination free of charge but can have it at their own expense. We investigated human papillomavirus vaccine uptake by men in Denmark and the socioeconomic factors that may predict human papillomavirus vaccination. METHODS: Using the Civil Registration System, we identified all boys and men aged 9-26 years in 2006-2013 and their mothers. By linkage to Statistics Denmark and the National Prescription Registry, we obtained information on socioeconomic variables and human papillomavirus vaccination during the study period. Using Cox regression, we examined the associations between socioeconomic variables and human papillomavirus vaccination. RESULTS: Between 2006 and 2013, 6253 (0.8%) males aged 9-26 years were vaccinated against human papillomavirus. The strongest predictor identified was ethnicity. Males who were immigrants (hazard ratio, 0.12; 95% confidence interval, 0.08-0.180) or sons of immigrant parents (hazard ratio, 0.13; 95% confidence interval, 0.10-0.17) were less likely to be vaccinated than Danish males. Additionally, sons of mothers who were unemployed, unmarried, had a low income, and basic education initiated human papillomavirus vaccination less frequently. Finally, sons of mothers who were physicians or nurses were more likely to be vaccinated than sons of other highly educated mothers. CONCLUSION: We found low uptake, with social disparities in human papillomavirus vaccination of boys and young men in Denmark.

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.

Trends in the incidence of cervical cancer and severe precancerous lesions in Denmark, 1997-2012.

PURPOSE: The incidence of cervical cancer, including squamous cell carcinoma (SCC), has been decreasing in several developed countries since the onset of organized screening programs; in some countries, however, the incidence of adenocarcinoma has increased among young women. We investigated the Danish incidence trends during 1997-2011 when cervical screening coverage was high. Incidences of cervical intraepithelial neoplasia grade 3 (CIN3) and adenocarcinoma in situ (AIS) were also assessed, with the latest part of the study period coinciding with introduction of free-of-charge human papillomavirus (HPV) vaccination. METHODS: Using nationwide registries, we estimated age-specific and age-standardized incidence rates and estimated annual percentage change (EAPC). RESULTS: The incidence of SCC decreased significantly, especially in women aged ≥45 years [EAPC: -3.1 % (95 % CI -4.3 to -2.5)], whereas the incidence of adenocarcinoma increased significantly, from 2.4 to 3.1/100,000 primarily due to increases in women aged ≤44 years [EAPC: 4.3 % (95 % CI 1.8-6.7)]. The incidences of CIN3 and AIS increased significantly from 94.7 to 156.5/100,000 and 3.3 to 11.3/100,000, respectively, but, importantly, they decreased significantly during 2009-2012 in women aged ≤20 years. CONCLUSIONS: The Danish screening program has successfully reduced the incidence of cervical cancer, especially of SCC in older women; however, the program has not significantly reduced the incidence in young women or the incidence of adenocarcinoma, which is increasing. Decreases in the incidences of CIN3 and AIS in age groups with high HPV vaccine coverage may herald a future decrease in cervical cancer incidence in young Danish women.

Incidence of cervical lesions in Danish women before and after implementation of a national HPV vaccination program.

PURPOSE: Approximately 70% of cervical cancers and about 50% of high-grade cervical precursor lesions are caused by human papillomavirus (HPV) types 16 and 18. Denmark introduced the quadrivalent HPV vaccine into the vaccination program for 12-year-old girls in 2009 supplemented by a first catch-up program for 13-15-year-old girls in 2008, and a second program for women up to the age of 27 years in 2012; all with high vaccination coverage. The aim of this study was to evaluate the effectiveness of the vaccine by comparing the incidence trends of cervical lesions before and after its introduction. METHODS: Incident cases of cervical lesions were identified from the nationwide Pathology Data Bank. Age-specific incidence rates were estimated for six age groups, and Poisson regression was used to calculate estimated annual percentage change (EAPC). RESULTS: The incidence of atypia or worse (atypia+) and cervical intraepithelial neoplasia grade 2 or worse (CIN2+) increased in all age groups in 2000-2010. After introduction of the quadrivalent HPV vaccine into the vaccination program, the incidence of atypia+ decreased significantly in women younger than 18 years (EAPC -33.4%; 95% CI -49.6; -12.0) and in 18-20-year-old women (EAPC -12.6%; 95% CI -19.3; -5.3). The incidence of CIN2+ also decreased significantly in 18-20-year-old women (EAPC -14.8%; 95% CI -21.6; -7.5) in 2010-2013, but no significant decrease was seen in older age groups. CONCLUSION: The incidence of cervical lesions decreased significantly in age groups with high HPV vaccine coverage, indicating an early effect of HPV vaccination.

Early impact of human papillomavirus vaccination on cervical neoplasia--nationwide follow-up of young Danish women.

BACKGROUND: In clinical trials, vaccines against human papillomavirus (HPV) have been highly effective against HPV16- or HPV18-associated cervical lesions. The quadrivalent HPV vaccine was licensed in 2006 and subsequently implemented in the Danish vaccination program. The study aim was to use individual information on HPV vaccination status to assess subsequent risk of cervical lesions. METHODS: Using a cohort study design, we identified all girls and women born in Denmark in the period from 1989 to 1999 and obtained information on individual HPV vaccination status in the period from 2006 to 2012 from nationwide registries. Incident cases of cervical lesions were identified by linkage to the nationwide Pathology Data Bank. We compared vaccinated and unvaccinated girls and women stratified by birth cohort in Cox proportional hazards models. RESULTS: Risk of atypia or worse (atypia+) and of cervical intraepithelial neoplasia grade 2 or 3 (CIN2/3) were statistically significantly reduced among vaccinated women in birth cohorts 1991 to 1994 (1991-1992atypia+: hazard ratio [HR] = 0.46, two-sided 95% confidence interval [CI] = 0.39 to 0.56; 1991-1992CIN2/3: HR = 0.56, 95% CI = 0.37 to 0.84; 1993-1994atypia+: HR = 0.40, 95% CI = 0.29 to 0.56; 1993-1994 CIN2/3: HR = 0.27, 95% CI = 0.10 to 0.67). The birth cohort 1989 to 1990 had a statistically significantly reduced risk of atypia+ (HR = 0.75; 95% CI = 0.65 to 0.86); the risk of CIN2/3 was also decreased but not statistically significant. No events occurred among girls in the birth cohort 1997 to 1999, whereas for the birth cohort 1995 to 1996 a hazard ratio could be calculated only for atypia+. CONCLUSIONS: Six years after licensure of the quadrivalent HPV vaccine in Denmark, a reduced risk of cervical lesions is observed at the population level.

Increased incidence of penile cancer and high-grade penile intraepithelial neoplasia in Denmark 1978-2008: a nationwide population-based study.

OBJECTIVE: To assess the trends in incidence of penile cancer during 1978-2008 and high-grade penile intraepithelial neoplasia (PIN2/3) during 1998-2008 in Denmark. METHODS: Using two nationwide registries, we estimated age- and period-specific incidence rates. Log-linear Poisson regression analysis was used to estimate average annual percentage change (AAPC) and 95% confidence intervals (CI). RESULTS: We identified 1,488 men with penile cancer and 285 men with PIN2/3. The incidence of penile cancer increased from 1.0 to 1.3 per 100,000 men-years in 1978-1979 to 2006-2008; this represented an AAPC of 0.8% (95% CI: 0.17-1.37). Squamous cell carcinoma (SCC) was the most common histological type (91.7%). The median age at diagnosis was 67 years, and the age-specific incidence rate of penile SCC increased with increasing age. The incidence rate of PIN2/3 increased significantly (0.5 to 0.9 per 100,000 men-years) in 1998-1999 to 2006-2008, and this represented an AAPC of 7.1% (95% CI: 3.30-11.05). CONCLUSIONS: The incidence of penile cancer increased in 1978-2008 in Denmark, and the same applied to PIN2/3 in 1998-2008. A high prevalence of human papillomavirus (HPV) and a low circumcision rate in Denmark may partly explain our results.