Andrea Gini

HPV vaccination with concomitant HPV-based screening of young women has been proposed for faster cervical cancer elimination. We describe the baseline results of a population-based trial of this strategy to reduce the incidence of HPV. All 89,547 women born 1994-1999 and resident in the capital region of Sweden were personally invited to concomitant HPV vaccination and HPV screening with 26,125 women (29.2%) enrolled between 2021-05-03 and 2022-12-31. Baseline HPV genotyping of cervical samples from the study participants finds, compared to pre-vaccination prevalences, a strong decline of HPV16 and 18 in birth cohorts previously offered vaccination, some decline for cross-protected HPV types but no decline for HPV types not targeted by vaccines. Our dynamic transmission modelling predicts that the trial could reduce the incidence of high-risk HPV infections among the 1994-1998 cohorts by 62-64% in 3 years. Baseline results are prevalences of HPV infection, validated transmission model projections, and power estimates for evaluating HPV incidence reductions at follow-up (+/−0.1% with 99.9% confidence). In conclusion, concomitant HPV vaccination and HPV screening appears to be a realistic option for faster cervical cancer elimination. Clinicaltrials.gov identifier: NCT04910802; EudraCT number: 2020-001169-34.

We describe a nationwide implementation trial of concomitant Human Papillomavirus (HPV) vaccination and HPV screening of young women to reduce the incidence of HPV and provide HPV screening-mediated protection against cervical cancer. All 89,547 women born 1994-1999 resident in the capital region of Sweden were personally invited to concomitant vaccination and screening with 26,125 women (29,2%) enrolling. HPV genotyping found a strong decline of HPV16 and 18 in birth cohorts previously offered vaccination, but no decline for HPV types not targeted by vaccines. Our dynamic transmission modelling predicted that the trial could reduce the incidence of high-risk HPV infections among the 1994-1998 cohorts by 64-69% in 3 years. At baseline, we demonstrated feasibility, validated transmission model projections, and obtained power estimates. At follow-up, the trial can estimate HPV incidence reductions of +/-0.1% with 99.9% confidence. Clinicaltrials.gov identifier: NCT04910802.

Supplementary Figure from Cost-Effectiveness of Colorectal Cancer Surveillance in Hodgkin Lymphoma Survivors Treated with Procarbazine and/or Infradiaphragmatic Radiotherapy

Background:Hodgkin lymphoma survivors treated with infradiaphragmatic radiotherapy (IRT) and/or procarbazine have an increased risk of developing colorectal cancer. We investigated the cost-effectiveness of colorectal cancer surveillance in Dutch Hodgkin lymphoma survivors to determine the optimal surveillance strategy for different Hodgkin lymphoma subgroups.Methods:The Microsimulation Screening Analysis-Colon model was adjusted to reflect colorectal cancer and other-cause mortality risk in Hodgkin lymphoma survivors. Ninety colorectal cancer surveillance strategies were evaluated varying in starting and stopping age, interval, and modality [colonoscopy, fecal immunochemical test (FIT, OC-Sensor; cutoffs: 10/20/47 μg Hb/g feces), and multi-target stool DNA test (Cologuard)]. Analyses were also stratified per primary treatment (IRT and procarbazine or procarbazine without IRT). Colorectal cancer deaths averted (compared with no surveillance) and incremental cost-effectiveness ratios (ICER) were primary outcomes. The optimal surveillance strategy was identified assuming a willingness-to-pay threshold of €20,000 per life-years gained (LYG).Results:Overall, the optimal surveillance strategy was annual FIT (47 μg) from age 45 to 70 years, which might avert 70% of colorectal cancer deaths in Hodgkin lymphoma survivors (compared with no surveillance; ICER:€18,000/LYG). The optimal surveillance strategy in Hodgkin lymphoma survivors treated with procarbazine without IRT was biennial FIT (47 μg) from age 45 to 70 years (colorectal cancer mortality averted 56%; ICER:€15,000/LYG), and when treated with IRT and procarbazine, annual FIT (47 μg) surveillance from age 40 to 70 was most cost-effective (colorectal cancer mortality averted 75%; ICER:€13,000/LYG).Conclusions:Colorectal cancer surveillance in Hodgkin lymphoma survivors is cost-effective and should commence earlier than screening occurs in population screening programs. For all subgroups, FIT surveillance was the most cost-effective strategy.Impact:Colorectal cancer surveillance should be implemented in Hodgkin lymphoma survivors.

Supplementary Data from Cost-Effectiveness of Colorectal Cancer Surveillance in Hodgkin Lymphoma Survivors Treated with Procarbazine and/or Infradiaphragmatic Radiotherapy

Supplementary Table from Cost-Effectiveness of Colorectal Cancer Surveillance in Hodgkin Lymphoma Survivors Treated with Procarbazine and/or Infradiaphragmatic Radiotherapy

Background:Hodgkin lymphoma survivors treated with infradiaphragmatic radiotherapy (IRT) and/or procarbazine have an increased risk of developing colorectal cancer. We investigated the cost-effectiveness of colorectal cancer surveillance in Dutch Hodgkin lymphoma survivors to determine the optimal surveillance strategy for different Hodgkin lymphoma subgroups.Methods:The Microsimulation Screening Analysis-Colon model was adjusted to reflect colorectal cancer and other-cause mortality risk in Hodgkin lymphoma survivors. Ninety colorectal cancer surveillance strategies were evaluated varying in starting and stopping age, interval, and modality [colonoscopy, fecal immunochemical test (FIT, OC-Sensor; cutoffs: 10/20/47 μg Hb/g feces), and multi-target stool DNA test (Cologuard)]. Analyses were also stratified per primary treatment (IRT and procarbazine or procarbazine without IRT). Colorectal cancer deaths averted (compared with no surveillance) and incremental cost-effectiveness ratios (ICER) were primary outcomes. The optimal surveillance strategy was identified assuming a willingness-to-pay threshold of €20,000 per life-years gained (LYG).Results:Overall, the optimal surveillance strategy was annual FIT (47 μg) from age 45 to 70 years, which might avert 70% of colorectal cancer deaths in Hodgkin lymphoma survivors (compared with no surveillance; ICER:€18,000/LYG). The optimal surveillance strategy in Hodgkin lymphoma survivors treated with procarbazine without IRT was biennial FIT (47 μg) from age 45 to 70 years (colorectal cancer mortality averted 56%; ICER:€15,000/LYG), and when treated with IRT and procarbazine, annual FIT (47 μg) surveillance from age 40 to 70 was most cost-effective (colorectal cancer mortality averted 75%; ICER:€13,000/LYG).Conclusions:Colorectal cancer surveillance in Hodgkin lymphoma survivors is cost-effective and should commence earlier than screening occurs in population screening programs. For all subgroups, FIT surveillance was the most cost-effective strategy.Impact:Colorectal cancer surveillance should be implemented in Hodgkin lymphoma survivors.

Supplementary Table from Cost-Effectiveness of Colorectal Cancer Surveillance in Hodgkin Lymphoma Survivors Treated with Procarbazine and/or Infradiaphragmatic Radiotherapy

Supplementary Table from Cost-Effectiveness of Colorectal Cancer Surveillance in Hodgkin Lymphoma Survivors Treated with Procarbazine and/or Infradiaphragmatic Radiotherapy

Supplementary Figure from Cost-Effectiveness of Colorectal Cancer Surveillance in Hodgkin Lymphoma Survivors Treated with Procarbazine and/or Infradiaphragmatic Radiotherapy