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Background Human papillomavirus (HPV) vaccination has shown high efficacy against anal HPV infection and lesions in clinical trials, and the HPV prevalence and type distribution in anal precancers and cancer predict a high preventable potential for HPV vaccination. However, the real-world effectiveness of HPV vaccination against anal high-grade lesions and cancer is yet to be shown. Methods We investigated HPV vaccine effectiveness against anal high-grade squamous intraepithelial lesion (HSIL) or worse in a nationwide cohort including all Danish women aged 17-32 years during October 2006 to December 2021 (n = 968 881). HPV vaccinations and first occurrence of anal HSIL or worse were retrieved from nationwide registries. Women were considered vaccinated after first dose and classified by age at vaccination. Using Cox regression, hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated for anal HSIL or worse according to vaccination status. Results During follow-up, the number of incident histological anal HSIL or worse cases was 37 in unvaccinated women, and less than 5 and 26 in women vaccinated at ages younger than 17 years and 17-32 years, respectively. The overall number of cancers was less than 5. Compared with unvaccinated women, the risk of histological anal HSIL or worse was reduced for women vaccinated at age younger than 17 years (HR = 0.30, 95% CI = 0.10 to 0.87). For women vaccinated at age 17-32 years, the hazard rate of anal HSIL or worse was 1.21 (95% CI = 0.73 to 2.03). Conclusion This is the first study to demonstrate that HPV vaccination at a younger age is associated with substantially reduced risk of anal HSIL or worse in the general population. [ABSTRACT FROM AUTHOR]

Background Increasing evidence suggests that 1-dose human papillomavirus (HPV) vaccination may protect significantly against HPV-related disease. We provide nationwide, real-world data on the risk of genital warts (GWs) after <3 vaccine doses. Methods All Danish women born in 1985–2003 were identified, and individual-level vaccination data were retrieved. The cohort was followed up for first occurrence of GWs until 31 December 2016. Using Poisson regression, we calculated incidence rates (IRs) of GWs per 100 000 person-years and IR ratios (IRRs) with corresponding 95% confidence intervals (CIs) for GWs, according to vaccination status, age at first dose, and calendar time. Results The cohort comprised 1 076 945 girls and women, of whom 485 408 were vaccinated. For girls initiating vaccination at age 12–14 years and 15–16 years, 1-dose vaccine effectiveness (VE) was 71% (IRR = 0.29; 95% CI,.22–.38) and 62% (0.38;.29–.49), respectively, compared with unvaccinated girls. In the same age groups, 2-dose VE was 78% (IRR, 0.22; 95% CI,.18–.26) and 68% (0.32;.26–.38), respectively. After 2009, the IRRs for 3 versus 1 dose and 2 versus 1 dose increased towards unity over calendar time, being 0.69 (95% CI,.57–.84) and 0.86 (.68–1.08) in 2016, respectively. Conclusions In this study, 1 or 2 doses of quadrivalent HPV vaccine was associated with substantial protection against GWs in girls vaccinated at age ≤16 years. The 1-dose VE approached that of 3 or 2 doses over calendar time, probably reflecting the impact of herd protection. [ABSTRACT FROM AUTHOR]

Background: The primary goal of human papillomavirus (HPV) vaccination is to reduce morbidity and mortality from HPV-associated disease, especially cervical cancer. We determined the real-world effectiveness of HPV vaccination against cervical cancer.Methods: The study included women aged 17-30 years living in Denmark October 2006-December 2019. From nationwide registries, information on HPV vaccination and cervical cancer diagnoses were retrieved. Incidence rate ratios (IRRs) with 95% confidence intervals (CIs) for cervical cancer according to vaccination status were estimated using Poisson regression with HPV vaccination treated as a time-varying variable and stratified by age at vaccination. We adjusted for attained age, education, and ethnicity. To address the effect of prevalent disease, different buffer periods were used, with 1-year buffer period as primary analysis.Results: The cohort comprised 867 689 women. At baseline, 36.3% were vaccinated at age 16 years and younger, and during follow-up, 19.3% and 2.3% were vaccinated at ages 17-19 years and 20-30 years, respectively. For women vaccinated at ages 16 years and younger or 17-19 years, the IRRs of cervical cancer were 0.14 (95% CI = 0.04 to 0.53) and 0.32 (95% CI = 0.08 to 1.28), respectively, compared with unvaccinated women. In women aged 20-30 years at vaccination, the incidence rate was higher than among unvaccinated women (IRR = 1.19, 95% CI = 0.80 to 1.79) but slightly decreased with increasing buffer period (IRR = 0.85, 95% CI = 0.55 to 1.32, with 4-year buffer period).Conclusion: HPV vaccine effectiveness against cervical cancer at the population level is high among girls vaccinated younger than age 20 years. The lack of immediate effect in women vaccinated at age 20-30 years points to the importance of early age at vaccination. [ABSTRACT FROM AUTHOR]

Background: Vaccination against human papillomavirus (HPV) has proven to be effective against severe cervical lesions and genital warts, whereas no previous study has provided real-world data on the HPV vaccine effectiveness against high-grade vulvovaginal lesions.Methods: A cohort of all women age 17-26 years living in Denmark during 2006-2019 was followed in nationwide registers for individual-level information about HPV vaccination and first diagnoses of vulvar and vaginal high-grade squamous intraepithelial lesions (HSIL+) or worse. The cumulative incidence of vulvar and vaginal HSIL+, respectively, was estimated with the Aalen-Johansen estimator, and Cox proportional hazards regression was used to estimate hazard ratios (HRs) for vulvar and vaginal lesions separately, comparing women vaccinated at age 16 years or younger and at age 17-26 years with unvaccinated women.Results: The cohort consisted of 514 537 women, of which 50.6% were vaccinated at baseline (<16 years), 31.8% were vaccinated during follow-up (17-26 years), and 17.6% remained unvaccinated. The cumulative incidence was less than 0.6‰ for vulvar HSIL+ and less than 0.2‰ for vaginal HSIL+. Adjusted analyses showed reduced HRs for both vulvar (HR = 0.22, 95% confidence interval = 0.13 to 0.38) and vaginal HSIL+ (HR = 0.16, 95% confidence interval = 0.04 to 0.55) for women vaccinated at age 16 years or younger compared with unvaccinated women. For women vaccinated at 17-26 years of age, the reductions in HRs were smaller for vaginal HSIL+ and close to 0 for vulvar HSIL+.Conclusions: HPV vaccination before 17 years of age reduces the risk of vulvar and vaginal HSIL+ based on real-world data. [ABSTRACT FROM AUTHOR]

Human papillomavirus (HPV) is essential for developing cervical cancer and precancerous lesions. Currently, three vaccines are available, which are effective as prophylaxis against HPV infection, however, limited knowledge exists about the possible effect of vaccinating women treated with conization to prevent recurrence. The aim of our study was to examine the risk of cervical intraepithelial neoplasia grade 2 or worse (CIN2+) after conization according to HPV vaccination status. Using Danish nationwide registries, we identified women diagnosed with CIN3 on the cone (2006–2012) and their HPV vaccination status. Vaccinees were defined as women vaccinated between 3 months before until 1 year after conization. The women were followed from 1 year after conization until diagnosis of CIN2+, conization, death, emigration or end of follow‐up. Cox proportional hazard regression was used to estimate hazard ratios (HRs) and corresponding 95% confidence intervals (CIs) of CIN2+ comparing vaccinees with nonvaccinees. The HR was adjusted for age, histology on cone, education, year of conization, repeat conizations and CIN2+ lesions between conization and start of follow‐up. Altogether 17,128 women were included (2,074 vaccinees). There was a statistically nonsignificant lower risk of CIN2+ among vaccinees (HRadjusted = 0.86, 95% CI: 0.67–1.09). Women vaccinated 0–3 months before tended to have a slightly lower HR of CIN2+ (HRadjusted = 0.77, 95% CI: 0.45–1.32) than women vaccinated 0–12 months after conization (HRadjusted = 0.88, 95% CI: 0.67–1.14), although not statistically significantly different. Our results add to the current knowledge about the potential clinical effect of vaccination as an adjunct to conization of high‐grade cervical neoplasia to decrease risk of recurrence. What's new? Vaccination against human papillomavirus (HPV) is an effective means of preventing cervical cancer in healthy women. Whether HPV vaccine can also prevent cervical malignancy in women previously treated with conization to remove abnormal cervical tissue, however, remains unknown. Here, women who received HPV vaccine three months before until one year after conization were found to have a marginally lower subsequent risk of cervical intraepithelial neoplasia grade 2 or worse (CIN2+), relative to unvaccinated women. While the results did not reach statistical significance, they suggest that HPV vaccination may be beneficial for women who have undergone conization. [ABSTRACT FROM AUTHOR]

In this registry‐based cohort study, we estimated the risk of human papillomavirus (HPV)‐related anogenital premalignancies and cancer in renal transplant recipients (RTRs) compared to a nontransplanted comparison cohort. We identified all first‐time RTRs in Denmark during 1990–2015 in a nationwide nephrology register. For each RTR, we randomly selected 50 age‐ and sex‐matched non‐RTRs from the background population. The study population was followed for diagnoses of cervical, vaginal, vulvar, penile and anal intraepithelial neoplasia grades 2–3 (IN2/3) and cancer for up to 27 years. We estimated hazard ratios (HRs) of anogenital IN2/3 and cancer in RTRs vs. non‐RTRs by Cox regression separately for men and women using age as underlying timescale, adjusting for income, education, HPV vaccination and immunocompromising conditions. We included 4,261 RTRs and 213,673 non‐RTRs. RTRs had increased hazard of cervical (HR = 2.1, 95% CI: 1.7–2.8), vaginal (HR = 35.0, 95% CI: 13.9–87.7), vulvar (HR = 16.4, 95% CI: 10.4–25.8), penile (HR = 21.9, 95% CI: 11.1–43.5) and anal (women: HR = 51.1, 95% CI: 28.0–93.1; men: HR = 39.0, 95% CI: 16.7–91.1) IN2/3. The HRs of anogenital cancers were also increased at most sites. The HR of anogenital IN2/3 in female RTRs tended to be higher during graft function than during dialysis. In female RTRs aged <40 years at transplantation, 10–15% had cervical IN2/3 and 5–12% had vaginal/vulvar/anal IN2/3 within 20 years after transplantation, compared to 4–8 and 0.2–0.4%, respectively, of female non‐RTRs. In conclusion, RTRs had substantially higher risk of HPV‐related anogenital premalignancies and cancer than non‐RTRs. What's new? Kidney transplant recipients are vulnerable to infections resulting from immunosuppressive treatments. As these patients live longer with their new organs, they also develop more cancer, especially cancers caused by viruses. Here, the authors investigated the rate of HPV‐related premalignancies in renal transplant recipients. Using data from Danish registries, they identified 4,200 renal transplant recipients and 210,000 randomly selected age‐ and sex‐matched controls. Looking at incidence of anogenital intraepithelial neoplasia and cancer over 27 years, they found that transplant recipients had substantially higher risk of developing lesions than healthy controls, and would potentially benefit from more vigilant screening. [ABSTRACT FROM AUTHOR]

Background A reduced, 2-dose schedule of human papillomavirus (HPV) vaccination has been endorsed for preadolescent women on the basis of immunogenicity data from randomized trials, and limited data suggest that even 1 dose may provide sufficient protection. Surveillance of the impact of <3 vaccine doses on clinical endpoints in the targeted age group is warranted. Methods We conducted a nationwide cohort study of all women aged 17–25 years, living in Denmark between 2006 and 2016. From nationwide registries, we extracted individual-level data on vaccination with the quadrivalent HPV (qHPV) vaccine at 16 years or younger, number of doses administered, diagnoses of cervical intraepithelial neoplasia grade 2 or worse (CIN2+) or grade 3 or worse (CIN3+), and potential confounders. Using Poisson regression, we estimated incidence rate ratios (IRRs) with 95% confidence intervals (CIs) for CIN2+ and CIN3+, according to vaccination status. Results The cohort comprised 590 083 women, of which 215 309 (36%) women were vaccinated at ≤16 years, and among these, 40 742 (19%) received <3 vaccine doses. A total of 5561 women had a diagnosis of CIN3+. We found considerable vaccine effectiveness against CIN3+ after 1 (IRR, 0.38 [95% CI,.14–.98]), 2 (IRR, 0.38 [95% CI,.22–.66]), or 3 (IRR, 0.37 [95% CI,.30–.45]) vaccine doses, compared to unvaccinated women. Results were similar for CIN2+. Conclusions We find substantial effectiveness of qHPV vaccination against high-grade cervical precancerous lesions, among women vaccinated with 1, 2, or 3 doses at ≤16 years of age. One-dose vaccination appeared to provide similar protection as 3-dose vaccination. [ABSTRACT FROM AUTHOR]

Highlights • Nationwide data from two countries covering more than 2 million women. • Young women vaccinated with 3 doses have reduced risk of severe cervical lesions. • In young women similar risk after 2 doses with 4 months apart compared to 3 doses. Abstract 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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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 [Cl] = 0.39 to 0.56; 1991-1992CIN2/3: HR = 0.56, 95% CI = 0.37 to 0.84; 1993-1994atipa+: HR = 0.40, 95% CI = 0.29 to 0.56; 1993-1994CIN2/3: 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% Cl = 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. [ABSTRACT FROM AUTHOR]

• Vaccines against HPV infection are highly effective when introduced before exposure to HPV. • Countries with a high HPV vaccine coverage have a strong impact on the burden of HPV-related disease. • We compare real-world evidence from two countries with different HPV vaccination policies. • Multi-cohort HPV vaccination has a greater impact on disease control than single-cohort approach. In 2009, both Norway and Denmark initiated routine quadrivalent human papillomavirus vaccination (qHPV) for 12-year-old girls; however, Denmark also introduced free-of-charge multi-cohort vaccination for older age groups in 2008. We aim to describe trends in genital warts (GWs) incidence rates (IRs) among men and women and qHPV vaccine coverage among women in Norway and Denmark in 2006–2015. We linked multiple national health registries in Norway and Denmark via national personal identifiers to access data on GWs incidence and qHPV vaccination among women and men aged 12–35 years residing in Norway and Denmark in 2006–2015. We calculated age-specific and age-standardized GWs IRs, GWs IR trends before (2006–2009) and after (2009–2015) the implementation of qHPV vaccination, and qHPV vaccine coverage among women. In Norway and Denmark together, there were more than 200,000 cases of incident GWs and over 710,000 girls got at least one dose of qHPV vaccine during the study period. The total qHPV coverage in Norway and Denmark in 2015 was among women aged 12–35 years 24% and 70%, respectively. GWs IRs in Norway and Denmark decreased annually in 2009–2015 among women by 4.8% (95% confidence interval: 4.3 to 5.3) and 18.0% (95%CI: 17.5 to 18.6), respectively, and among men 1.9% (95%CI: 1.4 to 2.4) and 10.7% (95%CI: 10.3 to 11.2), respectively. In Denmark, GWs IRs decreased rapidly among both sexes and all age groups after qHPV vaccination, while Norway showed only a modest decrease. Rapid decline in HPV-related morbidity is feasible with high coverage of multi-cohort vaccination. However, the decision to vaccinate a single cohort of 12-years-old girls only will postpone HPV-related disease control by at least a decade. Thus countries planning HPV vaccination programs should also initiate multi-cohort vaccination for faster disease control. [ABSTRACT FROM AUTHOR]

Highlights • There was no association between HPV vaccination and the risk of spontaneous abortion. • There was no association between HPV vaccination and the risk of stillbirth. • There was no association between HPV vaccination and one-year mortality. Abstract Background Few studies have studied the association between unintended human papillomavirus (HPV) vaccination and adverse pregnancy outcomes. This study set out to determine the association between HPV vaccination during pregnancy and subsequent risk of spontaneous abortion, stillbirth, and one-year infant mortality. Methods Population-based study including all pregnancies in Denmark (October 2006–December 2014) among women born 1975–1992. From nationwide health registries using the personal identification numbers, we obtained information on HPV vaccination, pregnancy outcomes, and infant mortality. The exposure window went from four weeks before conception date until 22 weeks of gestation for the outcome spontaneous abortion, and until birth for stillbirth and infant mortality outcomes. In the analyses of spontaneous abortion, we used time to event models, for stillbirth logistic regression models, and for infant mortality Cox regression was applied. Results We included 522,705 pregnancies for the outcome spontaneous abortion (7487 exposed to at least one dose during pregnancy); 351,878 births (5262 exposed to at least one dose during pregnancy) for the stillbirth; and 350,739 live births (5245 exposed to at least one dose during pregnancy) for infant mortality. No significantly increased rate of spontaneous abortion among women vaccinated during pregnancy compared with unvaccinated women was found. In addition, we found no association between HPV vaccination during pregnancy and stillbirth (adjusted odds ratio = 0.96 [95% CI: 0.57–1.61]), or infant mortality (adjusted hazard ratio = 0.94 [95% CI: 0.53–1.67]). A secondary analysis showed no association between number of doses and timing of administration (i.e. vaccination before or during pregnancy) and an increased risk of spontaneous abortion. Conclusion We found no increased risk of spontaneous abortion, stillbirth, or infant mortality following unintended HPV vaccination during pregnancy. [ABSTRACT FROM AUTHOR]

A response from the authors of the article "Strongly decreased genital warts after vaccination against human papillomavirus: Nationwide follow-up of vaccinated and unvaccinated girls in Denmark," published in a 2013 issue of "Clinical Infectious Diseases" is presented.