Supplementary Figure S1. Dilution curves of the type-specific ctHPV DNA assays.

Supplementary Figure S9. Number of copies of ctHPV DNA at different timepoints for all patients (n = 38) with only ctHPV DNA–negative samples at the end of treatment and early- and late follow-up who did not develop disease progression. Median follow-up time 37.5 months, range 18.3 – 50.0 months.

Supplementary Figure S4. Kaplan–Meier graphs of comparisons between patients with ctHPV DNA–positive (dotted, bottom lines) and ctHPV DNA–negative (solid, top lines) plasma at early-follow up/tumor evaluation (1-4 month after finished treatment) plasma.

Supplementary Table S3. ctHPV DNA copies in pretreatment plasma in correlation to tumor size and age at diagnosis.

Supplementary Figure S5. Progression-free survival according to complete clinical response or not, at tumor evaluation, approximately 3 months after finished treatment.

Supplementary Figure S3. Kaplan–Meier graphs of comparisons between patients with ctHPV DNA–positive (dotted, bottom lines) and ctHPV DNA–negative (solid, top lines) plasma at different timepoints.

Supplementary information on assay design.

Supplementary Table S1. Primers and probes used (Integrated DNA Technologies, Coralville, Iowa, USA).

Supplementary Figure S8. Number of copies of ctHPV DNA at different timepoints for all patients (n = 4) with at least one ctHPV DNA–positive sample during early- or late follow-up but no verified relapse.

Supplementary Figure S6. Number of copies of ctHPV DNA at different timepoints for all patients (n = 3) that were diagnosed with disease progression during or just at the end of treatment. Arrows indicate the approximate time of diagnosis of progression.

Supplementary Figure S2. Kaplan–Meier graphs comparing survival according to ctHPV DNA detection in pretreatment plasma.

Supplementary Figure S7. Number of copies of ctHPV DNA at different timepoints for all patients (n = 13) who experienced disease progression at early follow-up or tumor evaluation or shortly thereafter and thus were not deemed to have had complete response to treatment.

Supplementary results and discussion on normal cfDNA.

Supplementary Table S4. Normal cell-free DNA levels, using cell-free albumin DNA as a surrogate marker, in pretreatment plasma in relation to FIGO 2018 stage, HPV type, and histopathology.

Background: In Sweden, the cervical cancer screening programme is based on primary human papillomavirus (HPV) testing with either clinician-collected cervical sampling or home-based vaginal self-sampling. We assessed the effectiveness and cost-effectiveness of primary HPV clinician-collected sampling and primary HPV self-collected sampling for unvaccinated cohorts of Swedish women. Methods: A model-based analysis was performed to project long-term costs and quality-adjusted life-years (QALYs). Screening strategies included no screening, 18 clinician-collected strategies and 36 self-sampling strategies, with variations in the screening frequency, start age and follow-up management. We estimated incremental cost-effectiveness ratios benchmarked against willingness-to-pay (WTP) thresholds of 50,000EUR and 100,000EUR per QALY gained. Results: Compared with the 2022 recommendations (with primary clinician-collected HPV testing from ages 23 with 5-yearly screening to age 50 and 7-yearly screening through to age 64), self-sampling at the same intensity would lead to similar effectiveness and a 36% reduction in costs. Among the clinician-collected sampling strategies, the optimal strategies involved primary HPV testing from age 25 with 10-yearly screening with extended genotyping (at 50,000EUR per QALY gained), or 7- and 10-yearly screening for 100,000EUR. Across all strategies, the optimal strategies included primary self-sampling from age 25 with direct referral to colposcopy for HPV-16/18/45 with 7- and 10-yearly screening at 50,000EUR per QALY gained, and 5- and 7-yearly screening for 100,000EUR per QALY gained. These results were sensitive to the assumed accuracy of self-sampling compared with clinician-collected sampling. Conclusions: Transitioning from clinician-collected cervical sampling to vaginal HPV self-sampling is likely to be cost-effective for unvaccinated women in Sweden. ### Competing Interest Statement The authors have declared no competing interest. ### Funding Statement This work was supported by: the Swedish Cancer Society (Cancerfonden; grant No. CAN21/1512); Swedish Research Council (Vetenskapradet; grant No. VR 2022-00684 and the Swedish eScience Research Centre); and the European Commission (HEAP grant No. 874662). The funding sources had no involvement in the conduct of the research or preparation of the article. ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes All relevant data are within the manuscript and its Supporting Information files.

To examine health-related quality of life (HRQoL) and supportive care needs among young adult (YA) cancer survivors up to 3 years post-diagnosis. A national cohort of individuals diagnosed at 18–39 years with breast, cervical, ovarian, or testicular cancer, lymphoma or brain tumor was approached with surveys at 1.5 (n = 1010, response rate 67

Abstract Purpose: Human papillomavirus (HPV) is the cause of the majority of cervical cancer cases and has been showed to be released as cell-free tumor DNA (ctHPV DNA) into the circulation. Here, we analyze if ctHPV DNA could be used as a prognostic biomarker and/or to detect relapse earlier than traditional methods in locally advanced cervical cancer (LACC). Experimental Design: A total of 74 patients with LACC were included; 66of 74 were positive for 13 high-risk HPV types on a bead-based assay of tumor biopsy samples. HPV-type–specific droplet digital PCR assays were developed. Longitudinal plasma samples were then analyzed for the biopsy-verified HPV type for each patient. In total, 418 plasma samples were analyzed. Patients were followed for a median of 37 months. Results were correlated to tumor and clinical characteristics. Results: Of the pretreatment plasma samples, 92.4% were positive for ctHPV DNA. Persistent ctHPV DNA in end-of-treatment, early follow-up (1–2 months after end-of-treatment), or tumor evaluation (3–4 months after end-of-treatment) plasma was correlated with worse progression-free survival (P < 0.001) compared with if ctHPV DNA was not found. The positive predictive value of ctHPV status at early follow-up for predicting disease progression was 87.5%, and the negative predictive value was 89.3%. ctHPV DNA was found in plasma before relapse was diagnosed using radiology in all patients (n = 10) who experienced relapse after complete clinical response to treatment with a median 315 days lead time. Conclusions: ctHPV DNA in follow-up plasma is a promising prognostic biomarker in patients with LACC, useful for analysis of response to therapy and for early detection of relapse.