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Previous research has shown that women's use of a carrageenan gel reduces the risk of acquiring genital human papillomavirus (HPV) infections but does not help to clear existing ones. Although gel use may not result in complete clearance, it may decrease the viral load of HPV infections. We tested this hypothesis in the Carrageenan‐gel Against Transmission of Cervical Human papillomavirus (CATCH) randomized controlled trial. Participants of the CATCH study were selected for viral load testing if they had completed the first four study visits and tested positive for HPV42 or HPV51 in at least one of these visits. HPV42 and HPV51 were chosen as they were among the most abundant low‐ and high‐risk types, respectively, in the study sample. We measured viral load with a type‐specific real‐time polymerase chain reaction. Results were displayed using summary statistics. Of 461 enrolled participants, 39 were included in the HPV42 analysis set and 56 in the HPV51 analysis set. The median time between visits 1 and 4 was 3.7 months. The viral load (copies/cell) of HPV42 ranged from <0.001 to 13 434.1, and that of HPV51 from <0.001 to 967.1. The net median change in HPV42 viral load over all four visits was −1.04 copies/cell in the carrageenan and −147 copies/cell in the placebo arm (Wilcoxon rank sum test, p = 0.26). There was no net median change in HPV51 viral load over all four visits in either arm (p = 0.45). The use of a carrageenan‐based gel is unlikely to reduce the viral load of HPVs 42 or 51. [ABSTRACT FROM AUTHOR]

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]

The Lubricant Investigation in Men to Inhibit Transmission of human papillomavirus (HPV) Infection randomized control trial in gay, bisexual, and other men who have sex with men (gbMSM) found that carrageenan use neither reduced acquisition of anal HPV infections nor influenced infection clearance. To investigate carrageenan's lack of protective effect, we compared the change in anal HPV16 and HPV18 viral loads following carrageenan use against placebo. We restricted our analysis to participants who completed the first four study visits and had a valid baseline sample (n = 161, 54 HIV‐positive). Samples were tested for HPV detection using the linear array PCR assay. HPV16‐ and/or HPV18‐positive samples were tested for viral load using real‐time PCR. For participants who tested HPV16‐ (n = 29) or HPV18‐positive (n = 10) at least once across visits 1−4, we compared the change in type‐specific viral load between study arms using the Mann−Whitney U test. Although the median net change in HPV16 and HPV18 viral loads across visits 1‐4 was higher in the treatment than placebo arm (HPV16: 0.68 vs. 0.18 copies/cell, p = 0.60; HPV18: 18.32 vs. 10.12 copies/cell, p = 0.52), these differences were not statistically significant. Results were similar by HIV status. Carrageenan use did not impact anal HPV16 or HPV18 viral loads, which may further explain its lack of protective effect in gbMSM. [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]

The performance of cervical cancer screening will decline as a function of lower disease prevalence—a consequence of successful human papillomavirus (HPV) vaccination. Replacement of cytology with molecular HPV testing as the primary screening test and adoption of risk‐based screening, with less intense screening of vaccinated individuals and initiated at older ages is expected to improve efficiency. However, policy officials may decide to further reduce or eliminate screening as the ratio of benefits to harms continues to decline. To evaluate the level of risk currently tolerated for different cancers in the United States (ie, for which clinical guidelines do not recommend secondary prevention though effective screening methods exist), we used US cancer registry data to compare incidence (2008‐2012) and survival (1988‐2011) associated with different cancers for which organized screening is recommended and not recommended. The most common cancer at ages 70 to 74 years (ie, age group with highest cancer incidence and reasonable life expectancy to consider screening in the US) satisfying Wilson and Jungner's classic screening criteria was vulvar cancer (incidence = 9/100 000 females). In comparison, the incidence of cervical cancer among females 65 years of age (the upper recommended age limit for screening) was 13 cases per 100 000 females (low as a reflection of effective screening), whereas 10‐year survival was 66% (similar to vulvar cancer at 67%). Our approach of defining tolerable risk in cancer screening could help guide future decisions to modify cervical screening programs. [ABSTRACT FROM AUTHOR]

Background: The 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 .Methods: Data 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.Results: A 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 < .05) was observed for individual oncogenic types 16/18/31/33/45/52 and nononcogenic types 6/11/53/74. Efficacy against cervical abnormalities (all types) increased with severity, ranging from 27.7% (95% CI = 21.7% to 33.3%) to 58.7% (95% CI = 34.1% to 74.7%) for cytologic outcomes (low-grade squamous intraepithelial neoplasia lesion or greater, and high-grade squamous intraepithelial neoplasia lesion or greater, respectively) and 66.0% (95% CI = 54.4% to 74.9%) to 87.8% (95% CI = 71.1% to 95.7%) for histologic outcomes (CIN2+ and CIN3+, respectively). Comparing Costa Rica Vaccine Trial and Papilloma Trial Against Cancer in Young Adults results, there was no evidence of heterogeneity, except for type 51 (efficacy = -28.6% and 20.7%, respectively; two-sided P = .03).Conclusions: The AS04-HPV16/18 vaccine provides some additional cross-protection beyond established protected types, which partially explains the high efficacy against CIN3+. [ABSTRACT FROM AUTHOR]

Background: The incidence of oropharynx cancers has increased substantially in the United States. However, risk stratification tools for the identification of high-risk individuals do not exist. In this study, an individualized risk prediction model was developed and validated for oropharynx cancers in the US population.Methods: A synthetic, US population-based case-control study was conducted. Oropharynx cancer cases diagnosed at Ohio State University (n = 241) were propensity-weighted to represent oropharynx cancers occurring annually in the United States during 2009-2014 (n = 12,656). Controls (n = 9327) included participants in the National Health and Nutrition Examination Survey (2009-2014) and represented the annual US population aged 30 to 69 years (n = 154,532,508). The individualized 1-year absolute risk of oropharynx cancer was estimated with weighted logistic regression.Results: The risk prediction model included age, sex, race, smoking, alcohol use, lifetime sexual partners, and oral oncogenic human papillomavirus (HPV) status. The model had good discrimination and calibration in split-sample validation (area under the curve [AUC], 0.94; 95% confidence interval [CI], 0.92-0.97; observed/expected [O/E], 1.01; 95% CI, 0.70-1.32) and external validation (AUC, 0.87; 95% CI, 0.84-0.90; O/E, 1.08; 95% CI, 0.77-1.39). In the US population, 1-year predicted risks of oropharynx cancer were highest for older individuals (21.1/100,000 for 65- to 69-year-olds), men (13.9/100,000), whites (10.4/100,000), smokers (18.0/100,000 for >20 pack-years), heavy alcohol users (18.4/100,000), and those with prevalent oral oncogenic HPV (140.4/100,000). The risk prediction model provided substantial risk stratification, with approximately 77% of all oropharynx cancers and approximately 99% of HPV-positive oropharynx cancers occurring in the 10% of the US population with the highest model-predicted risk.Conclusions: This risk prediction model will enable the efficient design of studies to address the outstanding questions pertaining to the natural history, screening, and secondary prevention of oropharynx cancers. [ABSTRACT FROM AUTHOR]

Background: Oral tongue cancer incidence has increased among whites in the United States; however, the cause remains unknown. If an infectious agent is implicated, then elevated risk would be expected among immunosuppressed individuals.Methods: By using population-based registry linkage information from the US Transplant Cancer Match and human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS) Cancer Match studies, the authors examined the risk of oral tongue squamous cell carcinoma (SCC) among immunocompromised transplantation recipients and HIV-infected individuals. In addition, the risks of oropharyngeal SCC (strongly related to human papillomavirus infection; modestly affected by immunosuppression), other tobacco/alcohol-related oral cavity SCCs (not thought to be infection/immunosuppression-related), and non-Hodgkin lymphoma of oral cavity/pharynx (strongly related to Epstein-Barr virus; profoundly affected by immunosuppression) were evaluated.Results: Compared with the general population, the risk of non-Hodgkin lymphoma was strongly increased (standardized incidence ratio [SIR] > 8.0). The risk of all SCCs was modestly and similarly elevated among transplantation recipients (SIR range, 2.2-2.7; Pheterogeneity  = .2); whereas, among HIV-infected individuals, the risk of oral tongue SCC was higher compared with the risk of other SCCs (SIR, 3.0 vs 1.7 [for oropharyngeal SCCs] and 2.3 [for other oral cavity SCCs]; Pheterogeneity  < .001). The risk of SCCs was significantly higher among men, older individuals, and whites; and risk increased with the time since transplantation/AIDS onset. The risk of oral tongue SCC was significantly higher among HIV-infected men who have sex with men compared with the average risk in HIV-infected individuals (adjusted incidence rate ratio = 2.0).Conclusions: Similar modest increases in the risk of oral tongue and other oral cavity SCCs do not suggest that an infectious agent or exposure profoundly affected by immunosuppression underlies the increase in oral tongue cancer. Cancer 2018;124:2515-22. © 2018 American Cancer Society. [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]

Background: Millions of women have been vaccinated with one of two first-generation human papillomavirus (HPV) vaccines. Both vaccines remain in use and target two oncogenic types (HPVs 16 and 18); however, if these types naturally compete with others that are not targeted, type replacement may occur following reductions in the circulating prevalence of targeted types. To explore the potential for type replacement, we evaluated natural HPV type competition in unvaccinated females. Methods: Valid HPV DNA typing information was available from five epidemiological studies conducted in Canada and Brazil (n = 14,685; enrollment across studies took place between1993 and 2010), which used similar consensus-primer PCR assays, capable of detecting up to 40 HPV types. A total of 38,088 cervicovaginal specimens were available for inclusion in our analyses evaluating HPV type-type interactions involving vaccine-targeted types (6, 11, 16, and 18), and infection with each of the other HPV types. Results: Across the studies, the average age of participants ranged from 21.0 to 43.7 years. HPV16 was the most common type (prevalence range: 1.0% to 13.8%), and in general HPV types were more likely to be detected as part of a multiple infection than as single infections. In our analyses focusing on each of the vaccine-targeted HPV types separately, many significant positive associations were observed (particularly involving HPV16); however, we did not observe any statistically significant negative associations. Conclusions: Our findings suggest that natural HPV type competition does not exist, and that type replacement is unlikely to occur in vaccinated populations. [ABSTRACT FROM AUTHOR]

The article discusses evaluation of human papillomavirus (HPV) type replacement postvaccination. It mentions the need to distinguish increase in postvaccination from diagnostic artifacts consequent to consensus polymerase chain reaction (PCR) assays. It adds the use of multivariate logistic regression to evaluate association between HPV16 positivity and detection of HPV52.

Long-term survivors of pediatric and young adult (PAYA) cancers have a high incidence of subsequent neoplasms, but few risk factors other than cancer treatment have been identified. We aimed to describe the burden of human papillomavirus (HPV)-associated malignancies among survivors of PAYA cancers to assess whether HPV infections might be a reasonable area of future etiologic research on subsequent malignancies in this population. We used longitudinal data from 9 population-based registries of the Surveillance, Epidemiology, and End Results program collected between 1973 and 2010 to assemble a cohort of individuals who were diagnosed with any cancer between the ages of 0 and 29 years and survived at least 5 years post-diagnosis. We estimated sex-specific standardized incidence ratios (SIRs) with corresponding 95% confidence limits (CL) of HPV-associated subsequent malignancies (cervical, vaginal, vulvar, penile, anal, tongue, tonsillar, and oropharyngeal). Our study population comprised 64,547 long-term survivors of PAYA cancers diagnosed between 1973 and 2010. Compared with females in the general US population, female PAYA cancer survivors had a 40% relative excess of HPV-associated malignancies overall (SIR = 1.4, 95% CL: 1.2, 1.8). Compared with males in the general US population, male PAYA cancer survivors had a 150% relative excess of HPV-associated malignancies overall (SIR = 2.5, 95% CL: 1.9, 3.4). Our findings suggest an excess of HPV-associated malignancies among PAYA cancer survivors compared with the general US population. We hypothesize that a portion of subsequent malignancies among PAYA cancer survivors may be directly attributable to HPV infection. This hypothesis warrants exploration in future studies. [ABSTRACT FROM AUTHOR]