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BackgroundThe AS04-adjuvanted HPV16/18 (AS04-HPV16/18) vaccine provides excellent protection against targeted human papillomavirus (HPV) types and a variable degree of cross-protection against others, including types 6/11/31/33/45. High efficacy against any cervical intraepithelial neoplasia grade 3 or greater (CIN3+; >90%) suggests that lower levels of protection may exist for a wide range of oncogenic HPV types, which is difficult to quantify in individual trials. Pooling individual-level data from two randomized controlled trials, we aimed to evaluate AS04-HPV16/18 vaccine efficacy against incident HPV infections and cervical abnormalities .MethodsData were available from the Costa Rica Vaccine Trial (NCT00128661) and Papilloma Trial Against Cancer in Young Adults trial (NCT00122681), two large-scale, double-blind randomized controlled trials of the AS04-HPV16/18 vaccine. Primary analyses focused on disease-free women with no detectable cervicovaginal HPV at baseline.ResultsA total of 12 550 women were included in our primary analyses (HPV arm = 6271, control arm = 6279). Incidence of 6-month persistent oncogenic and nononcogenic infections, excluding known and accepted protected types 6/11/16/18/31/33/45 (focusing on 34/35/39/40/42/43/44/51/52/53/54/56/58/59/66/68/73/70/74), was statistically significantly lower in the HPV arm than in the control arm (efficacy = 9.9%, 95% confidence interval [CI] = 1.7% to 17.4%). Statistically significant efficacy (P

BackgroundThe AS04-adjuvanted HPV16/18 (AS04-HPV16/18) vaccine provides excellent protection against targeted human papillomavirus (HPV) types and a variable degree of cross-protection against others, including types 6/11/31/33/45. High efficacy against any cervical intraepithelial neoplasia grade 3 or greater (CIN3+; >90%) suggests that lower levels of protection may exist for a wide range of oncogenic HPV types, which is difficult to quantify in individual trials. Pooling individual-level data from two randomized controlled trials, we aimed to evaluate AS04-HPV16/18 vaccine efficacy against incident HPV infections and cervical abnormalities .MethodsData were available from the Costa Rica Vaccine Trial (NCT00128661) and Papilloma Trial Against Cancer in Young Adults trial (NCT00122681), two large-scale, double-blind randomized controlled trials of the AS04-HPV16/18 vaccine. Primary analyses focused on disease-free women with no detectable cervicovaginal HPV at baseline.ResultsA total of 12 550 women were included in our primary analyses (HPV arm = 6271, control arm = 6279). Incidence of 6-month persistent oncogenic and nononcogenic infections, excluding known and accepted protected types 6/11/16/18/31/33/45 (focusing on 34/35/39/40/42/43/44/51/52/53/54/56/58/59/66/68/73/70/74), was statistically significantly lower in the HPV arm than in the control arm (efficacy = 9.9%, 95% confidence interval [CI] = 1.7% to 17.4%). Statistically significant efficacy (P

Background International data on anogenital HPV infection incidence among men are limited. Methods Incidence of incident-persistent (IP) anogenital HPV infections was evaluated among 295 men who have sex with men (MSM) and 1576 heterosexual men (HM) aged 16–27 years in the placebo arm of a global, multicenter 4-valent (4v) HPV vaccine trial. We estimated IP incidence (penile/scrotal, perineal/perianal, anal) for 4vHPV and 9-valent (9v) HPV vaccine types and cumulative IP incidence over 36 months. Results IP infection incidence per 100 person-years (95% CI) among HM for 4vHPV and 9vHPV types was 4.1 (3.5–4.9) and 6.8 (5.9–7.6) at penile/scrotal, and 1.2 (.8–1.6) and 1.9 (1.5–2.4) at perineal/perianal sites, respectively; and among MSM, IP infection incidence was 2.3 (1.3–3.8) and 3.2 (2.0–4.9) at penile/scrotal, 6.8 (4.9–9.2) and 9.0 (6.9–11.6) at perineal/perianal, and 12.0 (9.4–15.1) and 16.8 (13.7–20.2) at anal sites, respectively. Cumulative IP incidence over 36 months (excluding anal canal; any 9vHPV type) was higher among MSM versus HM (24.1% vs 18.4%). Conclusions A substantial proportion of unvaccinated men of catch-up vaccination age developed IP 9vHPV-related infections. Gender-neutral vaccination could decrease male HPV infection, contribute to herd protection, and reduce disease burden. Clinical Trials Registration. NCT00090285. [ABSTRACT FROM AUTHOR]

In Denmark, vaccination against human papillomavirus (HPV) has been implemented in the children's vaccination program (January 2009) and in multiple catch‐up cohorts (October 2008 in girls 13‐15 years and in August 2012 in women up to 27 years). In the present study we estimate incidence of cervical intraepithelial neoplasia grade 3 (CIN3), adenocarcinoma in situ (AIS), squamous cell carcinoma (SCC) and adenocarcinoma (AC) during 2000‐2019. All cases of CIN3 and AIS were identified from the nationwide Pathology Data Bank, while SCC and AC were identified from the Danish Cancer Registry. We calculated age‐standardized incidence rates and estimated annual percentage change (EAPC) with corresponding 95% confidence interval (CI) for the periods before vaccination implementation (2000‐2005), early after implementation of childhood HPV vaccination and the first catch‐up vaccination program (2006‐2012), and after implementation of the second catch‐up program (2013‐2019). For CIN3 and AIS, age‐specific incidence rates and EAPCs were calculated. An increasing age‐standardized incidence was observed before introduction of HPV vaccination (2000‐2005) for CIN3 [EAPCCIN3: 3.0 (95% CI 1.7 to 4.3)] and AIS [EAPCAIS: 3.5 (95% CI 0.7 to 6.4)]. In the most recent period (2013‐2019), following implementation of the second catch‐up program, a decrease was observed for both CIN3 [EAPCCIN3: ‐6.5 (95% CI ‐8.3 to −4.8)], AIS [EAPCAIS: ‐8.7 (95% CI ‐12.3 to −5.1)] and for SCC [EAPCSCC: ‐3.9 (95% CI ‐7.5 to −0.2)]. In this study we document a decrease in the incidence of CIN3, AIS and SCC in the period after implementation of multi‐cohort HPV vaccination in Denmark. [ABSTRACT FROM AUTHOR]

Lung cancer is currently one of the most common malignant diseases and is responsible for substantial mortality worldwide. Compared with never smokers, former smokers remain at relatively high risk for lung cancer, accounting for approximately half of all newly diagnosed cases in the US. Screening offers former smokers the best opportunity to reduce their risk of advanced stage lung cancer and there is now evidence that annual screening using low-dose computed tomography (LDCT) is effective in preventing mortality. Studies are being conducted to evaluate whether the benefits of LDCT screening outweigh its costs and potential harms and to determine the most appropriate workup for patients with screen-detected lung nodules. Program efficiency would be optimized by targeting high-risk current smokers, but low uptake among this group is a concern. Former smokers may be invited for screening; however, if fewer long-term current smokers and more former smokers with long quit duration elect to attend, this could have very adverse effects on cost and screening test parameters. To illustrate this point, we present three possible screening scenarios with lung cancer prevalence ranging from between 0.62 and 5.0 %. In summary, cost-effectiveness of lung cancer screening may be improved if linked to successful smoking cessation programs and if better approaches are developed to reach very high-risk patients, e.g., long-term current smokers or others based on more accurate risk prediction models., Author(s): Joseph E. Tota[sup.1] [sup.2] , Agnihotram V. Ramanakumar[sup.1] , Eduardo L. Franco[sup.1] [sup.2] Author Affiliations: (1) Department of Oncology, McGill University, 546 Pine Avenue West, H2W1S6, Montreal, QC, Canada [...]

Background: Carrageenan, a non-toxic gelling agent derived from red algae, has potent anti-human papillomavirus (HPV) activity in in vitro and animal studies. We assessed, in an interim analysis, the efficacy of a carrageenan-based gel in reducing the risk of new detections of anal HPV among gay, bisexual and other men who have sex with men (gbMSM).Methods: The LIMIT-HPV study (Lubricant Investigation in Men to Inhibit Transmission of HPV Infection) is a phase IIb, double-blind, placebo-controlled randomised controlled trial conducted in Montreal, Canada. gbMSM were randomly assigned (1:1) to receive a carrageenan-based or placebo gel. Participants were instructed to apply the gel to the anus, condom and/or partners' penis before and-as required-during receptive anal intercourse. Questionnaire data and anal samples were collected at 0, 1, 2, 3, 6, 9 and 12 months. We estimated new detections of anal HPV infection(s) detected via Linear Array using Cox proportional hazards models.Results: Participants recruited from February 2016 to December 2019 were randomly assigned to the carrageenan (n=127) or placebo (n=128) arm. The efficacy and safety analyses included 201 and 210 participants. The median follow-up time was 7.6 months (range: 0-28.5) in the carrageenan group and 9.3 months (range: 0-40.7) in the placebo group. The HR for new detections was 1.21 (95% CI 0.86 to 1.70): 69.4% and 65.1% new detections of HPV in the carrageenan and placebo arms, respectively. More adverse events were reported in the carrageenan (59.8%) compared with the placebo (39.8%) arm.Conclusions: The interim analysis did not demonstrate a protective effect of carrageenan on the risk of new detections of anal HPV infection among gbMSM. Carrageenan gel use was associated with a higher proportion of adverse events. Given these findings and the (assumed) low probability that a beneficial effect would be found by the study's end, the trial was terminated as recommended by the Data Safety and Monitoring Board.Trial Registration Number: NCT02354144. [ABSTRACT FROM AUTHOR]

Background In men, the incidence of human papillomavirus (HPV)–related cancer is rising, but data regarding male HPV infection and seroprevalence are available from only a few countries. Methods This analysis of a global HPV vaccine trial evaluated baseline data from 1399 human immunodeficiency virus–negative heterosexual men (HM) and men who have sex with men (MSM). Key objectives included assessment of HPV prevalence and risk factors for seropositivity to 9-valent HPV (9vHPV) vaccine types (6, 11, 16, 18, 31, 33, 45, 52, and 58), and concordance between seropositivity and prevalent HPV type. Results Overall, 455 of 3463 HM (13.1%) and 228 of 602 MSM (37.9%) were HPV DNA positive for any 9vHPV vaccine type at baseline. Infection prevalence and seroprevalence (≥1 9vHPV vaccine type) were 13.2% and 8.1%, respectively, among 333 HM from Europe, and 37.9% and 29.9%, respectively, among 335 MSM from Europe or North America. Among men with baseline infection, MSM had higher seroprevalence for concordant HPV types (39.5% vs 10.8% in HM). The seropositivity risk (irrespective of baseline infection status) was higher among MSM versus HM (age-adjusted odds ratio, 3.0 [95% confidence interval, 2.4–6.4]). Among MSM, statistically significant seropositivity risk factors included younger age at sexual debut, higher number of receptive anal sex partners, and less frequent condom use. No factors assessed were associated with seropositivity in HM. Conclusions Higher proportions of MSM than HM were HPV DNA positive and seropositive, and concordance between HPV DNA positivity and seropositivity, a potential marker of true infection versus carriage, was higher in MSM. Most MSM and HM were seronegative for all 9vHPV vaccine types, suggesting the potential benefit of catch-up vaccination after sexual debut. Clinical Trials Registration. NCT00090285. [ABSTRACT FROM AUTHOR]

Clinical trial data and real-world evidence suggest that the AS04-adjuvanted vaccine targeting human papillomavirus types 16 and 18 (AS04-HPV-16/18) vaccine provides nearly 90% protection against cervical intraepithelial neoplasia grade 3 or higher irrespective of type, among women vaccinated before sexual debut. This high efficacy is not fully explained by cross-protection. Although AS04-HPV-16/18 vaccination does not affect clearance of prevalent infections, it may accelerate clearance of newly acquired infections. We pooled data from 2 large-scale randomized controlled trials to evaluate efficacy of the AS04-HPV-16/18 vaccine against clearance of nontargeted incident infections. Results of our analysis do not suggest an effect in expediting clearance of incident infections. [ABSTRACT FROM AUTHOR]

Background: Current HPV vaccines do not protect against all oncogenic HPV types. Following vaccination, type replacement may occur, especially if different HPV types competitively interact during natural infection. Because of their common route of transmission, it is difficult to assess type interactions in observational studies. Our aim was to evaluate type replacement in the setting of HPV vaccine randomized controlled trials (RCTs).Methods: Data were pooled from the Costa Rica Vaccine Trial (CVT; NCT00128661) and PATRICIA trial (NCT001226810)-two large-scale, double-blind RCTs of the HPV-16/18 AS04-adjuvanted vaccine-to compare cumulative incidence of nonprotected HPV infections across trial arms after four years. Negative rate difference estimates (rate in control minus vaccine arm) were interpreted as evidence of replacement if the associated 95% confidence interval excluded zero. All statistical tests were two-sided.Results: After applying relevant exclusion criteria, 21 596 women were included in our analysis (HPV arm = 10 750; control arm = 10 846). Incidence rates (per 1000 infection-years) were lower in the HPV arm than in the control arm for grouped nonprotected oncogenic types (rate difference = 1.6, 95% confidence interval [CI] = 0.9 to 2.3) and oncogenic/nononcogenic types (rate difference = 0.2, 95% CI = -0.3 to 0.7). Focusing on individual HPV types separately, no deleterious effect was observed. In contrast, a statistically significant protective effect (positive rate difference and 95% CI excluded zero) was observed against oncogenic HPV types 35, 52, 58, and 68/73, as well as nononcogenic types 6 and 70.Conclusion: HPV type replacement does not occur among vaccinated individuals within four years and is unlikely to occur in vaccinated populations. [ABSTRACT FROM AUTHOR]