The efficacy and effectiveness of the quadrivalent human papillomavirus (HPV) vaccine in preventing high-grade cervical lesions have been shown. However, data to inform the relationship between quadrivalent HPV vaccination and the subsequent risk of invasive cervical cancer are lacking.

The incidence of cancer is continuing to rise and risk-tailored early diagnostic and/or primary prevention strategies are urgently required. The ideal risk-predictive test should: integrate the effects of both genetic and nongenetic factors and aim to capture these effects using an approach that is both biologically stable and technically reproducible; derive a score from easily accessible biological samples that acts as a surrogate for the organ in question; and enable the effectiveness of risk-reducing measures to be monitored. Substantial evidence has accumulated suggesting that the epigenome and, in particular, DNA methylation-based tests meet all of these requirements. However, the development and implementation of DNA methylation-based risk-prediction tests poses considerable challenges. In particular, the cell type specificity of DNA methylation and the extensive cellular heterogeneity of the easily accessible surrogate cells that might contain information relevant to less accessible tissues necessitates the use of novel methods in order to account for these confounding issues. Furthermore, the engagement of the scientific community with health-care professionals, policymakers and the public is required in order to identify and address the organizational, ethical, legal, social and economic challenges associated with the routine use of epigenetic testing.

Since the licensure of the quadrivalent human papillomavirus (qHPV) vaccine in 2006 and the later licensure of the bivalent HPV (bHPV) vaccine, more than 175 million doses have been distributed worldwide.¹ The introduction of large-scale vaccination in a new target group—girls and young women—has been accompanied by a number of safety concerns, with the potential to undermine public confidence in the new vaccines.^2-5 One concern is the development of multiple sclerosis, which has been fuelled by social and news media reports of cases occurring after HPV vaccination¹ together with an increasing number of case reports published in the medical literature describing vaccinees who developed multiple sclerosis as well as other demyelinating diseases, including optic neuritis, transverse myelitis, acute disseminated encephalomyelitis, and neuromyelitis optica.^6-10 These concerns have been highlighted by the Global Advisory Committee on Vaccine Safety of the World Health Organization and were considered in a safety assessment conducted by the European Medicines Agency.^1,11 Potential mechanisms by which vaccines could induce autoimmune diseases have been suggested to include molecular mimicry and bystander activation.¹² It is, however, not known if the occurrence of these conditions after HPV vaccination merely reflects the background rates in girls and young women or represents a true increased risk. The few published analytical studies investigating the association between HPV vaccines and multiple sclerosis and other demyelinating diseases, while largely finding no significantly increased risks, have had limited statistical power to exclude even moderate to large increased risks of these conditions.^13-15

Human papillomavirus (HPV) types 16/18, included in HPV vaccines, contribute to the majority of cervical cancer, and a substantial proportion of cervical intraepithelial neoplasia (CIN) grades 2/3 or worse (CIN2+/CIN3+) including adenocarcinoma in situ or worse. The aim of this study was to quantify the effect of quadrivalent HPV (qHPV) vaccination on incidence of CIN2+ and CIN3+. A nationwide cohort of girls and young women resident in Sweden 2006–2013 and aged 13–29 (n = 1,333,691) was followed for vaccination and histologically confirmed high‐grade cervical lesions. Data were collected using the Swedish nationwide healthcare registers. Poisson regression was used to calculate incidence rate ratios (IRRs) and vaccine effectiveness [(1‐IRR)x100%] comparing fully vaccinated with unvaccinated individuals. IRRs were adjusted for attained age and parental education, and stratified on vaccination initiation age. Effectiveness against CIN2+ was 75% (IRR = 0.25, 95%CI = 0.18–0.35) for those initiating vaccination before age 17, and 46% (IRR = 0.54, 95%CI = 0.46–0.64) and 22% (IRR = 0.78, 95%CI = 0.65–0.93) for those initiating vaccination at ages 17–19, and at ages 20–29, respectively. Vaccine effectiveness against CIN3+ was similar to vaccine effectiveness against CIN2+. Results were robust for both women participating to the organized screening program and for women at prescreening ages. We show high effectiveness of qHPV vaccination on CIN2+ and CIN3+ lesions, with greater effectiveness observed in girls younger at vaccination initiation. Continued monitoring of impact of HPV vaccination in the population is needed in order to evaluate both long‐term vaccine effectiveness and to evaluate whether the vaccination program achieves anticipated effects in prevention of invasive cervical cancer.

Cervical cancer (CC) screening in women comprises human papillomavirus (HPV) testing followed by cytology triage of positive cases. Drawbacks, including cytology’s low reproducibility and requirement for short screening intervals, raise the need for alternative triage methods. Here we used an innovative triage technique, the WID-qCIN test, to assess the DNA methylation of human genes DPP6, RALYL and GSX1 in a real-life cohort of 28,017 women aged ≥30 years who attended CC screening in Stockholm between January and March 2017. In the analysis of all 2,377 HPV-positive samples, a combination of WID-qCIN (with a predefined threshold) and HPV16 and/or HPV18 (HPV16/18) detected 93.4% of cervical intraepithelial neoplasia grade 3 and 100% of invasive CCs. The WID-qCIN/HPV16/18 combination predicted 69.4% of incident cervical intraepithelial neoplasia grade 2 or worse compared with 18.2% predicted by cytology. Cytology or WID-qCIN/HPV16/18 triage would require 4.1 and 2.4 colposcopy referrals to detect one cervical intraepithelial neoplasia grade 2 or worse, respectively, during the 6 year period. These findings support the use of WID-qCIN/HPV16/18 as an improved triage strategy for HPV-positive women.

In this population‐based survey undertaken in Sweden in 2007, we investigated correlates of attitudes to human papillomavirus (HPV) vaccination among parents of children aged 12–15 years. We invited 16,000 parents of girls and 4,000 parents of boys, randomly selected from the Swedish population. Response rates were 70 and 69%, respectively. Multinomial logistic regression models were applied to investigate correlates of acceptability to HPV vaccination. Among studied parents, 76% were willing to vaccinate their child if the vaccine is for free and 63% were willing to vaccinate even if the vaccine comes with a cost. Having heard of HPV was associated with both willingness to vaccinate if the vaccine is free (odds ratio [OR]: 1.42; 95% confidence interval [CI]: 1.21–1.66) and willingness to vaccinate even if the vaccine is not free (OR: 1.96; 95% CI: 1.75–2.20) compared with those who never heard of HPV. Beliefs about vaccine safety and efficacy were also strong correlates of willingness to vaccinate. Parents born outside Europe and those with higher education were less willing to vaccinate if the vaccine is not free. In conclusion, the willingness to vaccinate was reasonably high and cost did not appear to be a major barrier. Information about vaccine safety and efficacy is important and parents need information about HPV and the HPV vaccine.