Objective Surgical intervention remains the cornerstone of treatment for gynecologic malignancies. However, the complex nature of these procedures leads to a significant risk of perioperative and post-operative complications. The European Society of Gynecological Oncology recognized the need for standardized, evidence-based consensus statements with the aim to minimize surgical morbidity and mortality and decrease surgical complications. Methods A literature review was conducted by the methodologist of the group, using the MEDLINE database, based on 5 patient, intervention or exposure, comparison or control, outcome frameworks. Literature published between January 1, 2014, and June 1, 2025, was reviewed and critically appraised. The literature search was limited to publications in English. Priority was given to high-quality systematic reviews, meta-analyses, and randomized controlled trials, but studies with less evidence, such as prospective cohort studies and retrospective registry-based analyses, were also evaluated. Statements were subsequently drafted collaboratively based on the review of the literature and adapted in an iterative process in conference call meetings including anonymous voting for each statement. Results The group achieved consensus on 26 statements categorized into six primary surgical domains: Energy Devices and Surgical Environment, Minimally Invasive Entry Techniques, Use of Uterine Manipulators, Lymphedema Prevention and Management, Vulvar Surgery and Wound Management, and Inguinal Lymphadenectomy. Conclusions This Consensus Statement presents comprehensive guidelines for the prevention of surgical complications in gynecologic oncology. These recommendations are expected to standardize surgical care, reduce perioperative morbidity and lead to improvement of post-operative recovery and ultimately quality of life of patients with gynecologic malignancies.

Lynch syndrome (LS) is a hereditary condition associated with an increased susceptibility to developing cancer, primarily colorectal and gynaecological cancer (endometrial cancer and ovarian cancer). The European Society of Gynaecological Oncology (ESGO) nominated fifteen practicing multidisciplinary clinicians with expertise in this field and ten gynaecological and oncological fellows with interest in the topics to develop evidence-based statements, sharing and standardizing the management of LS carriers. Published evidence was integrated with clinical experience to reach Consensus Statements through anonymous voting. In this Consensus, thirty-one statements based on the best available evidence and expert agreement are offered. They focused on genetic and cancer risk counseling principles, screening procedures, risk-reducing surgical and medical strategies, and address emerging topics such as reproductive issues for LS carriers, which are important in current practice. This manuscript reports the Statements that reached a consensus, their voting results, and a summary of supporting evidence.

Evidence on the diagnosis and management of women with primary lymphoma of the uterine cervix (PLUC) is limited. The present study performed a systematic review of the literature and provided an overview of the reported cases of PLUC. A total of 213 reports were included, which comprised 339 patients with PLUC. The mean age of the patients was 48.5 years (median, 46 years; age range, 15-88 years). The most common presenting symptom was vaginal bleeding (189/318, 59.4%) and its duration ranged from 4.5 days to 24 months, with only a small fraction of patients developing 'B' symptoms including weight loss, night sweats and fever (28/318, 8.8%). Biopsy (either excisional or punch biopsy) was the most commonly used initial/primary diagnostic modality (78/278, 28.1%) followed by ultrasound (59/278, 21.2%). The most common management approach out of 309 patients was surgery (with or without adjuvant or neo-adjuvant treatment; 115/309), followed by chemotherapy alone (109/309), which was followed by chemo-radiotherapy alone (62/309). The follow-up period for survivors ranged from 4 weeks to 246 months, and the absolute 5-year and 10-year survival rates were 86.1 and 85.4%, respectively. The relatively low number of patients and high heterogeneity did not permit a robust comparative analysis of the survival outcomes. However, the longest median survival was reported for women who received neo-adjuvant chemotherapy followed by surgery (15 patients; 72 months). Although malignant PLUC is rare, early detection, optimal therapeutic management, and multidisciplinary involvement of gynecologic oncologists and lymphoma specialists may offer benefit to patients diagnosed with this rare disease.

Histological diagnosis of cervical intraepithelial neoplasia grade 2 (CIN2) has traditionally been the cutoff for local surgical treatment, due to a substantial risk of cancer development. However, evidence from the past decade suggests 50-60% of CIN2 lesions spontaneously regress, and active surveillance (or conservative management-ie, leaving the lesion untreated) might be justified in some cases. Active surveillance of CIN2 lesions is now practised widely, although clear recommendations on eligibility, frequency of surveillance, threshold for treatment, and criteria for return to routine recall are insufficient in most countries. In 2023, the cumulative risk of invasive cancer over 20 years was found to be substantially higher in patients under active surveillance when compared with patients who received immediate local treatment, with the greatest difference observed in women older than 30 years. This Policy Review and practice algorithm from the British Society of Colposcopy and Cervical Pathology and the European Society of Gynaecologic Oncology prevention committees aims to review existing evidence and present clear recommendations to assist clinical decision making. Active surveillance, rather than immediate treatment, might be reasonable in a carefully selected cohort of patients. The risk of progression, need for repeat visits, and cumulative risk of future invasion associated with active surveillance should be carefully balanced against the benefits of awaiting regression, including consideration of the woman's age, fertility wishes, additional risk factors, and likelihood of compliance to follow-up. Clinical audit and, ideally, prospective databases are required to monitor long-term outcomes and safety.

BACKGROUND:The humoral and T-cell responses to booster COVID-19 vaccine types in multidisease immunocompromised individuals who do not generate adequate antibody responses to two COVID-19 vaccine doses, is not fully understood. The OCTAVE DUO trial aimed to determine the value of third vaccinations in a wide range of patients with primary and secondary immunodeficiencies. METHODS:OCTAVE-DUO was a prospective, open-label, multicentre, randomised, controlled, phase 3 trial investigating humoral and T-cell responses in patients who are immunocompromised following a third vaccine dose with BNT162b2 or mRNA-1273, and of NVX-CoV2373 for those with lymphoid malignancies. We recruited patients who were immunocompromised from 11 UK hospitals, aged at least 18 years, with previous sub-optimal responses to two doses of SARS-CoV-2 vaccine. Participants were randomly assigned 1:1 (1:1:1 for those with lymphoid malignancies), stratified by disease, previous vaccination type, and anti-spike antibody response following two doses. Individuals with lived experience of immune susceptibility were involved in the study design and implementation. The primary outcome was vaccine-specific immunity defined by anti-SARS-CoV-2 spike antibodies (Roche Diagnostics UK and Ireland, Burgess Hill, UK) and T-cell responses (Oxford Immunotec, Abingdon, UK) before and 21 days after the third vaccine dose analysed by a modified intention-to-treat analysis. The trial is registered with the ISRCTN registry, ISRCTN 15354495, and the EU Clinical Trials Register, EudraCT 2021-003632-87, and is complete. FINDINGS:Between Aug 4, 2021 and Mar 31, 2022, 804 participants across nine disease cohorts were randomly assigned to receive BNT162b2 (n=377), mRNA-1273 (n=374), or NVX-CoV2373 (n=53). 356 (45%) of 789 participants were women, 433 (55%) were men, and 659 (85%) of 775 were White. Anti-SARS-CoV-2 spike antibodies measured 21 days after the third vaccine dose were significantly higher than baseline pre-third dose titres in the modified intention-to-treat analysis (median 1384 arbitrary units [AU]/mL [IQR 4·3-7990·0] compared with median 11·5 AU/mL [0·4-63·1]; p<0·001). Of participants who were baseline low responders, 380 (90%) of 423 increased their antibody concentrations to more than 400 AU/mL. Conversely, 166 (54%) of 308 baseline non-responders had no response after the third dose. Detectable T-cell responses following the third vaccine dose were seen in 494 (80%) of 616 participants. There were 24 serious adverse events (BNT612b2 eight [33%] of 24, mRNA-1273 12 [50%], NVX-CoV2373 four [17%]), two (8%) of which were categorised as vaccine-related. There were seven deaths (1%) during the trial, none of which were vaccine-related. INTERPRETATION:A third vaccine dose improved the serological and T-cell response in the majority of patients who are immunocompromised. Individuals with chronic renal disease, lymphoid malignancy, on B-cell targeted therapies, or with no serological response after two vaccine doses are at higher risk of poor response to a third vaccine dose. FUNDING:Medical Research Council, Blood Cancer UK.

Whilst SARS-CoV-2 mRNA vaccines generate high neutralising antibodies (nAb) in most individuals, haematopoietic stem cell transplant (HSCT) and chimeric antigen receptor T-cell (CAR-T) recipients respond poorly. HSCT/CAR-T treatment ablates existing immune memory, with recipients requiring revaccination analogous to being vaccine naive. An optimal revaccination strategy for this cohort has not been defined. Factors predicting immunogenicity following three ancestral SARS-CoV-2 vaccines were assessed in 198 HSCT/CAR-T recipients and 96 healthcare workers (HCWs) recruited to multicentre studies. Only 25% of HSCT/CAR-T recipients generated nAbs following one dose, with titres 167-fold and 7-fold lower than that in HCWs after the first and second doses, respectively. Lower post-second dose nAb titres were associated with older age, rituximab use, and previous HSCT. ChAdOx1-S recipients were more likely to generate nAbs compared with mRNA vaccines, with titres comparable to HCWs. In contrast, nAbs were significantly lower in HSCT/CAR-T recipients than HCWs after mRNA vaccination. The poor first-dose immunogenicity in HSCT/CAR-T recipients suggests a minimum licensed dosing interval could limit the period of vulnerability following HSCT/CAR-T. The relative preservation of nAbs with ChAdOx1-S vaccination highlights the importance of evaluating alternative platforms to mRNA vaccination within this highly vulnerable clinical cohort.

Background Persistent infection by oncogenic human papillomavirus (HPV) is necessary although not sufficient for development of cervical cancer. Behavioural, environmental, or comorbid exposures may promote or protect against malignant transformation. Randomised evidence is limited and the validity of observational studies describing these associations remains unclear. Methods In this umbrella review, we searched electronic databases to identify meta-analyses of observational studies that evaluated risk or protective factors and the incidence of HPV infection, cervical intra-epithelial neoplasia (CIN), cervical cancer incidence and mortality. Following re-analysis, evidence was classified and graded based on a pre-defined set of statistical criteria. Quality was assessed with AMSTAR-2. For all associations graded as weak evidence or above, with available genetic instruments, we also performed Mendelian randomisation to examine the potential causal effect of modifiable exposures with risk of cervical cancer. The protocol for this study was registered on PROSPERO (CRD42020189995). Results We included 171 meta-analyses of different exposure contrasts from 50 studies. Systemic immunosuppression including HIV infection (RR = 2.20 (95% CI = 1.89–2.54)) and immunosuppressive medications for inflammatory bowel disease (RR = 1.33 (95% CI = 1.27–1.39)), as well as an altered vaginal microbiome (RR = 1.59 (95% CI = 1.40–1.81)), were supported by strong and highly suggestive evidence for an association with HPV persistence, CIN or cervical cancer. Smoking, number of sexual partners and young age at first pregnancy were supported by highly suggestive evidence and confirmed by Mendelian randomisation. Conclusions Our main analysis supported the association of systemic (HIV infection, immunosuppressive medications) and local immunosuppression (altered vaginal microbiota) with increased risk for worse HPV and cervical disease outcomes. Mendelian randomisation confirmed the link for genetically predicted lifetime smoking index, and young age at first pregnancy with cervical cancer, highlighting also that observational evidence can hide different inherent biases. This evidence strengthens the need for more frequent HPV screening in people with immunosuppression, further investigation of the vaginal microbiome and access to sexual health services.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) immune responses and infection outcomes were evaluated in 2,686 patients with varying immune-suppressive disease states after administration of two Coronavirus Disease 2019 (COVID-19) vaccines. Overall, 255 of 2,204 (12%) patients failed to develop anti-spike antibodies, with an additional 600 of 2,204 (27%) patients generating low levels (<380 AU ml −1 ). Vaccine failure rates were highest in ANCA-associated vasculitis on rituximab (21/29, 72%), hemodialysis on immunosuppressive therapy (6/30, 20%) and solid organ transplant recipients (20/81, 25% and 141/458, 31%). SARS-CoV-2-specific T cell responses were detected in 513 of 580 (88%) patients, with lower T cell magnitude or proportion in hemodialysis, allogeneic hematopoietic stem cell transplantation and liver transplant recipients (versus healthy controls). Humoral responses against Omicron (BA.1) were reduced, although cross-reactive T cell responses were sustained in all participants for whom these data were available. BNT162b2 was associated with higher antibody but lower cellular responses compared to ChAdOx1 nCoV-19 vaccination. We report 474 SARS-CoV-2 infection episodes, including 48 individuals with hospitalization or death from COVID-19. Decreased magnitude of both the serological and the T cell response was associated with severe COVID-19. Overall, we identified clinical phenotypes that may benefit from targeted COVID-19 therapeutic strategies.

PDF file - 237KB, Supplementary Table 1: Published Studies of Putative Functional SNPs Supplementary Table 2a: Drug Regimens and Doses of Taxanes by Study Supplementary Table 2b: Comparison of Toxicity grades/rates by recruiting trial in PGSNPS included in Taxane Related Sensory Neuropathy Study Supplementary Table 3: PGSNPS Taxane Treated Patient Characteristics Supplementary Table 4: All Putative Functional SNPs Replicated in the PGSNPS dataset (phenotype: cumulative dose to TRSN) Supplementary Table 5: All Putative Functional SNPs Replicated in the PGSNPS dataset (phenotype: maximum TRSN) Supplementary Figure 1: Percentage of Patients with TRSN ≥ grade 2 by genotype, for three statistically significant SNPs that were genotyped in PGSNPS (maximum TRSN) Supplementary Figures 2a-c: Kaplan-Meier curves Kaplan-Meier curves: Shows for each SNP, by genotype, the probability of TRSN grade 0-1 (i.e., the probability of not experiencing moderate/severe TRSN) as the cumulative dose increases.

Background: Optimal SARS-CoV-2 vaccination strategy in immunocompromised individuals who fail to mount adequate antibody responses to two vaccine doses is unknown. Methods: OCTAVE-DUO was a prospective, open-label, multi-centre, phase III trial investigating humoral and T-cell responses in immunocompromised patients following a third vaccine dose with BNT162b2 or mRNA-1273, and for lymphoid malignancies, NVX-CoV2373. It recruited immunocompromised patients from 11 UK hospitals, aged >18 years, with prior sub-optimal responses to two doses of SARS-CoV-2 vaccine. Participants were randomised 1:1 (1:1:1 for lymphoid malignancies), stratified by disease, previous vaccination type, and anti-spike antibody response following two doses.The primary outcome was vaccine-specific immunity defined by anti-spike SARS-CoV-2 antibody (Roche Elecsys) and T-cell responses (Oxford Immunotec) prior to and 21 days post third dose analysed by a modified intention to treat analysis.ISRCTN 15354495. Trial is closed. Findings: Between 4-Aug-2021 and 31-Mar-2022, 804 participants across nine disease cohorts were randomised to BNT162b2 (n=377), 374 mRNA-1273 (n=374), and NVX-CoV2373 (n=53).The third vaccine dose induced significantly higher anti-spike antibody levels than pre-third dose (baseline) levels. 90% of participants who were baseline low responders increased their antibody levels to above 400AU/mL. Conversely, 54% of baseline non-responders had no response. Detectable T-cell responses following the third vaccine dose were observed in 80% participants.Age >75 years, B-cell targeted therapies, anti-metabolites, or calcineurin inhibitors increased the risk of a serological non-response to the third vaccine. Similarly, a lack of T-cell response post two doses, age >75 years and treatment with calcineurin inhibitors, or corticosteroids reduced the likelihood of a T-cell response. Interpretation: A third vaccine dose improved the serological and T-cell response in the majority of immunocompromised patients. Individuals with chronic renal disease, lymphoid malignancy, B-cell targeted therapies, or an absent response after two vaccine doses are at higher risk of poor response. Trial Registration: The trial was registered on ISRCTN 15354495 (26-Jul-2021) and the EU Clinical Trials Register with EudraCT number 2021-003632-87 (29-Jun-2021). Registration to both was prospective, prior to recruitment of the first patient on 04-Aug-2021.Funding: Medical Research Council [grant number MR/W020653/1]Blood Cancer UK [award reference 21023].Declaration of Interest: DR research funding/honoraria and/or consultancy fees from Novartis, Pfizer, Lily Roche, Astra Zeneca/Diiachi Sankyo, Biotheranostics, RNA diagnostics, and Celgene; EB research funding and/or consultancy fees from Roche, Vaccitech and AZ, holds patents in ChAdOx1 HBV and HCV vaccines; HP honoraria from AZ; IMB research funding and/or consultancy fees from Abbvie, Amgen, BMS, Causeway Therapeutics Cabaletta, Eli Lilly, Evelo, Gilead, GSK, Janssen, Novartis, Pfizer, Sanofi Regeneron, and UCB Pharma; KO royalties to institution from Telix Pharmaceuticals for Radiolabelled anti-CD66 antibody; KLY honoraria from Sanofi Genzyme, Takeda, Amgen and meeting attendance support from Takeda; MJA research funding from Pfizer; MW research funding from Oxford Immunotech; MBCK honoraria from Gilead; MC consultancy fees from VacciTech; PK research funding and/or consultancy fees from Bayer, AZ, Merck and BMS; SM stock or stock options in TCB BioPharm; SHL honoraria from AZ; SS research funding and/or consultancy fees from AbbVie, Amgen (previously Celgene), Boehringer-Ingelheim, Bristol-Myers Squibb, Eli Lilly, GSK, Janssen, and UCB; and SOB research funding and/or consultancy fees from CSL Behring, GSK, Baxalta US Inc and Biotest. All other authors declare no conflicts of interest.Ethical Approval: The trial was conducted in accordance with the principles of the Good Clinical Practice (GCP) guidelines and the Declaration of Helsinki. It was approved by the UK Medicines and Healthcare Products Regulatory Agency (MHRA) on the 19-Jul-2021 and the first amendment approved on 23 -Jul-2021 by MHRA and the London and Fulham Research Ethics Committee (REC 302634). Subsequent amendments were approved by MHRA on 13-Oct-2021, 26-Nov-2021 and 14-Jun-2022 and by REC on 01-Nov-2021, 03-Dec-2021, and 06-Jun-2022. A separate CAR T-cell therapy disease cohort was introduced in the November amendment. The trial was overseen by an independent Data Monitoring Committee. All patients gave written informed consent.

Introduction/Background Epigenetic alterations are essential in the development of many cancers and can occur years in advance of histopathological change. Interest in methylation testing for enhanced cervical screening is increasing but epigenome-wide exploration has been limited and the best methylation markers are yet unknown. In this epigenome-wide association study (EWAS) of >850,000 methylation sites, we are the first to explore DNA methylation signatures associated to CIN3 and cervical cancer, to better understand potential drivers of cervical carcinogenesis and estimate performance of methylation as a diagnostic test. Methodology 247 women (119 normal, 74 CIN3/CGIN and 54 cervical cancer) attending gynaecological appointments or oncological treatment between 2014–2020 were recruited. Methylation signatures were obtained following bisulphite conversion of DNA extracted from exfoliated cervical cells and sequenced using the Illumina 850k array. After data QC, logistic regression and a conditional analysis were used to test for independent associations between methylation CpG sites and CIN3 or Cancer. P-values were Bonferroni corrected and adjusted for batch, chip, age and HPV status. Diagnostic test accuracy was estimated and tested in an independent cohort. Results 409 CpG methylation sites were strongly associated with CIN3 or cancer (P <5x10–8). Two CpG sites located in PAX1 and NREP-AS1 genes were found to be independently associated with CIN3/Cancer. Combining sites into a bigenic marker led to an AUC of 0.92 in a separate subset of the discovery cohort and 0.77 in an independent cohort of CIN3 cases. Conclusion This is potentially the first study to highlight epigenome-wide epigenetic signatures associated to CIN3 and cervical cancer. Functional annotation highlighted several genes related to tumour suppressor function and apoptosis are increasingly methylated in CIN3 and cervical cancer. PAX1 and NREP-AS1 as a methylation test has the potential to increase the accuracy of cervical screening through enhanced detection of women with CIN3 or cancer and future self-sampling. Disclosures This work was funded by NIHR and the Wellcome Trust. The authors have no conflicts of interest to declare.

Aims: SECRAB was a prospective, open-label, multicentre, randomised phase III trial comparing synchronous to sequential chemoradiotherapy (CRT). Conducted in 48 UK centres, it recruited 2297 patients (1150 synchronous and 1146 sequential) between 2 July 1998 and 25 March 2004. SECRAB reported a positive therapeutic benefit of using adjuvant synchronous CRT in the management of breast cancer; 10-year local recurrence rates reduced from 7.1% to 4.6% (P = 0.012). The greatest benefit was seen in patients treated with anthracycline-cyclophosphamide, methotrexate, 5-fluorouracil (CMF) rather than CMF. The aim of its sub-studies reported here was to assess whether quality of life (QoL), cosmesis or chemotherapy dose intensity differed between the two CRT regimens. Materials and methods: The QoL sub-study used EORTC QLQ-C30, EORTC QLQ-BR23 and the Women's Health Questionnaire. Cosmesis was assessed: (i) by the treating clinician, (ii) by a validated independent consensus scoring method and (iii) from the patients' perspective by analysing four cosmesis-related QoL questions within the QLQ-BR23. Chemotherapy doses were captured from pharmacy records. The sub-studies were not formally powered; rather, the aim was that at least 300 patients (150 in each arm) were recruited and differences in QoL, cosmesis and dose intensity of chemotherapy assessed. The analysis, therefore, is exploratory in nature. Results: No differences were observed in the change from baseline in QoL between the two arms assessed up to 2 years post-surgery (Global Health Status: -0.05; 95% confidence interval -2.16, 2.06; P = 0.963). No differences in cosmesis were observed (via independent and patient assessment) up to 5 years post-surgery. The percentage of patients receiving the optimal course-delivered dose intensity (>= 85%) was not significantly different between the arms (synchronous 88% versus sequential 90%; P = 0.503). Conclusions: Synchronous CRT is tolerable, deliverable and significantly more effective than sequential, with no serious disadvantages identified when assessing 2-year QoL or 5-year cosmetic differences. (C) 2023 The Authors. Published by Elsevier Ltd on behalf of The Royal College of Radiologists. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).

Introduction Human papillomavirus (HPV) is necessary but not sufficient for cervical cancer development. During cervical carcinogenesis, methylation levels increase across host and HPV DNA. DNA methylation has been proposed as a test to diagnose cervical intraepithelial neoplasia (CIN); we present a protocol to evaluate the accuracy of methylation markers to detect high-grade CIN and cervical cancer.Methods and analysis We will search electronic databases (Medline, Embase and Cochrane Library), from inception, to identify studies examining DNA methylation as a diagnostic marker for CIN or cervical cancer, in a cervical screening population. The primary outcome will be to assess the diagnostic test accuracy of host and HPV DNA methylation for high-grade CIN; the secondary outcomes will be to examine the accuracy of different methylation cut-off thresholds, and accuracy in high-risk HPV positive women. Our reference standard will be histology. We will perform meta-analyses using Cochrane guidelines for diagnostic test accuracy. We will use the number of true positives, false negatives, true negatives and false positives from individual studies. We will use the bivariate mixed effect model to estimate sensitivity and specificity with 95% CIs; we will employ different bivariate models to estimate sensitivity and specificity at different thresholds if sufficient data per threshold. For insufficient data, the hierarchical summary receiver operating curve model will be used to calculate a summary curve across thresholds. If there is interstudy and intrastudy variation in thresholds, we will use a linear mixed effects model to calculate the optimum threshold. If few studies are available, we will simplify models by assuming no correlation between sensitivity and specificity and perform univariate, random-effects meta-analysis. We will assess the quality of studies using QUADAS-2 and QUADAS-C.Ethics and dissemination Ethical approval is not required. Results will be disseminated to academic beneficiaries, medical practitioners, patients and the public.PROSPERO registration number CRD42022299760.

Human papillomavirus (HPV) is detected in 99.7% of cervical cancers. Current vaccines target types 16 and 18. Prior to vaccination implementation, a prospective cohort study was conducted to determine baseline HPV prevalence in unvaccinated women in Wales; after HPV16 and HPV18, HPV 51 was found to be most prevalent. This study aimed to re-assess the unexpected high prevalence of HPV 51 and consider its potential for type-replacement. Two hundred HPV 51 positive samples underwent re-analysis by repeating the original methodology using HPV 51 GP5+/6+ PCR-enzyme immunoassay, and additionally a novel assay of HPV 51 E7 PCR. Data were correlated with age, social deprivation and cytology. Direct repeat of HPV 51 PCR-EIA identified 146/195 (75.0%) samples as HPV 51 positive; E7 PCR identified 166/195 (85.1%) samples as HPV 51 positive. HPV 51 prevalence increased with cytological grade. The prevalence of HPV 51 in the pre-vaccinated population was truly high. E7 DNA assays may offer increased specificity for HPV genotyping. Cross-protection of current vaccines against less-prevalent HPV types warrants further study. This study highlights the need for longitudinal investigation into the prevalence of non-vaccine HPV types, especially those phylogenetically different to vaccine types for potential type-replacement. Ongoing surveillance will inform future vaccines.

Additional file 2. Costing spreadsheet.

Background The risk of cutaneous squamous cell carcinoma (cSCC) is significantly increased in organ transplant recipients (OTRs). Clearance of actinic keratoses (AKs) is generally regarded as a surrogate biomarker for cSCC prevention. OTR-cSCC chemoprevention with topical AK treatments has not been investigated in randomized controlled trials (RCTs), although there is evidence that 5% 5-fluorouracil (5-FU) may be chemoprotective in immunocompetent patients. Objectives To assess the feasibility, activity and evaluation outcomes relevant to the design of a future phase III RCT of topical cSCC chemoprevention in OTRs. Methods OTRs with 10 or more AKs in predefined areas were randomized 1 : 1 : 1 to topical 5-FU, 5% imiquimod (IMIQ) or sunscreen (sun-protective factor 30+) in a phase II, open-label RCT over 15 months. Feasibility outcomes included proportions of eligible OTRs randomized, completing treatment and willing to be re-treated. AK activity [AK clearance, new AK development, patient-centred outcomes (toxicity, health-related quality of life, HRQoL)] and evaluation methodology (clinical vs. photographic) were assessed. Results Forty OTRs with 903 AKs were randomized. All feasibility outcomes were met (56% of eligible OTRs were randomized; 89% completed treatment; 81% were willing to be re-treated). AK activity analyses found 5-FU and IMIQ were superior to sunscreen for AK clearance and prevention of new AKs. 5-FU was more effective than IMIQ in AK clearance and prevention in exploratory analyses. Although toxicity was greater with 5-FU, HRQoL outcomes were similar. Conclusions Trials of topical AK treatments in OTRs for cSCC chemoprevention are feasible and AK activity results support further investigation of 5-FU-based treatments in future phase III trials.