Publications by authors named "Rolando Herrero"

279 Publications

Germline determinants of humoral immune response to HPV-16 protect against oropharyngeal cancer.

Nat Commun 2021 10 12;12(1):5945. Epub 2021 Oct 12.

Section of Hygiene, University Department of Life Sciences and Public Health, Università Cattolica del Sacro Cuore, Roma, Italy.

Although several oropharyngeal cancer (OPC) susceptibility loci have been identified, most previous studies lacked detailed information on human papillomavirus (HPV) status. We conduct a genome-wide analysis by HPV16 serology status in 4,002 oral cancer cases (OPC and oral cavity cancer (OCC)) and 5,256 controls. We detect four susceptibility loci pointing to a distinct genetic predisposition by HPV status. Our most notable finding in the HLA region, that is now confirmed to be specific of HPV(+)OPC risk, reveal two independent loci with strong protective effects, one refining the previously reported HLA class II haplotype association. Antibody levels against HPV16 viral proteins strongly implicate the protective HLA variants as major determinants of humoral response against L1 capsid protein or E6 oncoprotein suggesting a natural immune response against HPV(+)OPC promoted by HLA variants. This indicates that therapeutic vaccines that target E6 and attenuate viral response after established HPV infections might protect against HPV(+)OPC.
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http://dx.doi.org/10.1038/s41467-021-26151-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8511029PMC
October 2021

Factors influencing participation in preventive interventions for gastric cancer: the results from the GISTAR study.

Eur J Cancer Prev 2021 Sep 13. Epub 2021 Sep 13.

Institute of Clinical and Preventive Medicine and Faculty of Medicine, University of Latvia Department of Research, Riga East University hospital Digestive Diseases Centre GASTRO Institute of Information Technology, Riga Technical University, Riga, Latvia International Agency for Research on Cancer (IARC), Lyon, France Centro Javeriano de Oncología, Hospital Universitario San Ignacio. Bogotá, Colombia Agencia Costarricense de Investigaciones Biomédicas, Fundación INCIENSA, San Jose, Costa Rica.

Objectives: Search-and-treat strategy for Helicobacter pylori and surveillance of patients with precancerous lesions are recommended to decrease the burden of gastric cancer in high-risk areas. We aimed to evaluate the acceptance of the target population to these strategies.

Methods: We applied a search-and-treat strategy combined with biomarker screening (pepsinogens I and II, gastrin-17) for atrophic gastritis to healthy individuals aged 40-64 years within the GISTAR Pilot study. Different means of invitation were evaluated - direct telephone calls, letters of invitation via the general practitioners. Participants with altered biomarker results were invited to undergo upper gastrointestinal endoscopy. H.pylori positive individuals were offered eradication therapy. Data on the compliance to the treatment and reasons for noncompliance were collected via telephone.

Results: Altogether 3453 participants were enrolled. The attendance of women participants was 1.9 times higher although active invitation strategies were mainly targeting men. The yield for the telephone invitations was higher than for mail-delivered invitations (2.1 calls vs. 7.7 letters required to recruit one study subject). Out of 661 individuals reached with the invitation to undergo upper endoscopy, 520 (78.7%) attended the procedure. Out of 1185 study subjects eligible for eradication, 810 (68.4%) accepted it. Of those having received the medication, 765(94.4%) completed it. The reasons for nonparticipation were the overall misconception of the importance of screening, busy schedule and others.

Conclusions: While only the minority of the target population participated in the gastric cancer prevention strategy, relatively high compliance was seen among the participants. The acceptance rate and the identified reasons for refusing to participate in our study indicate that there is a need to raise gastric cancer awareness and its existent preventive strategies within the general population for their successful implementation in the community.
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http://dx.doi.org/10.1097/CEJ.0000000000000682DOI Listing
September 2021

Infection with Human Papilloma Virus (HPV) and risk of subsites within the oral cancer.

Cancer Epidemiol 2021 Dec 9;75:102020. Epub 2021 Sep 9.

Department of Medical and Surgical Sciences, University of Bologna, Bologna, Italy; Stony Brook Cancer Center, Stony Brook University, Stony Brook, NY, USA. Electronic address:

Background: The aim of this study was to investigate the relationship between high-risk genotypes of Human Papilloma Virus (HPV) and cancer of different subsites of the oral cavity.

Material And Methods: A pooled analysis of five studies included on the International Head and Neck Cancer Epidemiology (INHANCE) Consortium was conducted. HPV 16 and HPV 18 were considered. Adjusted odds ratios (ORs) and corresponding 95 % confidence intervals (CIs) for HPV and each oral cavity subsites were simultaneously estimated using multinomial logistic regression models.

Results: The analysis included 1157 cases and 3272 controls. This study showed a slightly higher prevalence of HPV infection among oral cancer cases than controls. In particular, an increased risk of other and not otherwise specified (NOS) sites within the oral cavity, oral tongue, palate and floor of mouth cancer was observed for overall HPV16 positivity (OR = 1.66, 95 % CI: 1.01-2.72; OR = 1.97, 95 % CI: 1.36-2.85; OR = 2.48, 95 % CI: 1.50-4.11; OR = 2.71, 95 % CI: 1.06-6.95, respectively). In particular, HPV16E7 was related to cancer of floor of mouth, oral cavity NOS and palate (OR = 2.71, 95 % CI: 1.06-6.95; OR = 3.32, 95 % CI:1.53-7.19; OR = 3.34, 95 % CI:1.38-8.06). Results were inconsistent for HPV18 due to low prevalence of infection.

Conclusion: Our study suggests that HPV16 infection may increase the risk of developing floor of mouth, gum, tongue, and palate cancers.

Clinical Relevance: Subjects with HPV infection have a higher risk of cancer from all sites of the oral cavity.
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http://dx.doi.org/10.1016/j.canep.2021.102020DOI Listing
December 2021

Reproducibility, Temporal Variability, and Concordance of Serum and Fecal Bile Acids and Short Chain Fatty Acids in a Population-Based Study.

Cancer Epidemiol Biomarkers Prev 2021 Oct 10;30(10):1875-1883. Epub 2021 Aug 10.

Division of Cancer Epidemiology and Genetics, Metabolic Epidemiology Branch, National Cancer Institute, National Institutes of Health, Rockville, Maryland.

Background: Bile acid (BA) and short chain fatty acid (SCFA) production is affected by diet and microbial metabolism. These metabolites may play important roles in human carcinogenesis.

Methods: We used a fully quantitative targeted LC-MS/MS system to measure serum and fecal BA and SCFA concentrations in 136 Costa Rican adults at study baseline and 6-months. We randomly selected 50 participants and measured their baseline samples in duplicate. Our objective was to evaluate: Technical reproducibility; 6-month temporal variability; and concordance between sample type collected from the same individual at approximately the same time.

Results: Technical reproducibility was excellent, with intraclass correlation coefficients (ICC) ≥0.83 for all BAs except serum tauroursodeoxycholic acid (ICC = 0.72) and fecal glycolithocholic acid (ICC = 0.66) and ICCs ≥0.81 for all SCFAs except serum 2-methylbutyric acid (ICC = 0.56) and serum isobutyric acid (ICC = 0.64). Temporal variability ICCs were generally low, but several BAs (i.e., deoxycholic, glycoursodeoxycholic, lithocholic, taurocholic, and tauroursodeoxycholic acid) and SCFAs (i.e., 2-methylbutyric, butyric, propionic, and valeric acid) had 6-month ICCs ≥0.44. The highest degree of concordance was observed for secondary and tertiary BAs.

Conclusions: Serum and fecal BAs and SCFAs were reproducibly measured. However, 6-month ICCs were generally low, indicating that serial biospecimen collections would increase statistical power in etiologic studies. The low concordance for most serum and fecal metabolites suggests that consideration should be paid to treating these as proxies.

Impact: Our findings will inform the design and interpretation of future human studies on associations of BAs, SCFAs, and potentially other microbial metabolites, with disease risk.
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http://dx.doi.org/10.1158/1055-9965.EPI-21-0361DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8608567PMC
October 2021

Reduction of HPV16/18 prevalence in young women after eight years of three- and two-dose vaccination schemes.

Vaccine 2021 07 25;39(32):4419-4422. Epub 2021 Jun 25.

Escuela de Salud Pública de México, Instituto Nacional de Salud Pública, Av. Universidad 655, Cuernavaca, Morelos 62100, México. Electronic address:

Background: Recommendations for human papillomavirus vaccination have relied on immunogenicity studies and efficacy results derived from adult women. Insufficient information exists regarding HPV effectiveness in vaccinated girls as they become sexually active, regardless of dose scheme. We aimed to compare the prevalence of high-risk HPV between unvaccinated and vaccinated young women eight years after immunization.

Methods: After eight years, we recontacted women who received two-dose of bivalent or three-dose-either bivalent or quadrivalent-, HPV vaccine when aged 9-10 years-old as part of a clinical trial. Additionally, we recruited a contemporaneous unvaccinated woman group for comparison. Only those sexually active were included. High-risk HPV DNA was determined in urine samples and compared across groups.

Results: The prevalence of HPV16/18 types was 6.8% (95 %CI 3.2-14.1%) in the unvaccinated (n = 6/88), 1.1% (95 %CI 0.2-5.8%) in the three-dose (n = 1/93), and 0.0% (95 %CI 0.0-7.0%) in the two-dose group (n = 0/51).

Conclusion: HPV vaccination, with two-dose of bivalent or three-dose schemes-either with the bivalent or quadrivalent vaccine-, was associated with a lower prevalence of HPV16/18 types eight years after primary immunization.
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http://dx.doi.org/10.1016/j.vaccine.2021.06.040DOI Listing
July 2021

Recent progress in gastric cancer prevention.

Best Pract Res Clin Gastroenterol 2021 Mar-Apr;50-51:101733. Epub 2021 Feb 18.

Agencia Costarricense de Investigaciones Biomédicas, Fundación INCIENSA, Costa Rica. Electronic address:

Gastric cancer remains a major challenge to public health on a global scale, causing the loss of 19 million disability-adjusted life years worldwide in 2017. The future burden will increase due to population growth and ageing. Considering its absolute burden and persisting disparities, in addition to the substantial prevalence of Helicobacter pylori infection worldwide that is treatable, gastric cancer is a logical target for urgent global action for prevention. In this review, we discuss recent progress in gastric cancer prevention and propose a concerted international effort to implement population-based H. pylori treatment programmes, as the best evidence-based strategy that is currently available for gastric cancer prevention, in the context of demonstration projects in selected populations, to be later scaled up. It is time for urgent action to reduce the important loss of life and productivity caused by this preventable malignancy.
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http://dx.doi.org/10.1016/j.bpg.2021.101733DOI Listing
May 2021

Prevalence and Potential Risk Factors of Helicobacter pylori Infection among Asymptomatic Individuals in Kazakhstan.

Asian Pac J Cancer Prev 2021 02 1;22(2):597-602. Epub 2021 Feb 1.

Institute of Clinical and Preventive Medicine, University of Latvia, Riga, Latvia.

Background: Helicobacter pylori (H. pylori) infection is associated with several risk factors such as demographic, socioeconomic status and personal habits, which vary in different populations. This is the most up-to-date data on H. pylori prevalence and potential risk factors for H. pylori infection among asymptomatic middle-aged individuals in Kazakhstan.

Methods: Apparently healthy individuals aged 40 to 64, who took part in the health control in the outpatient clinic, were invited to participate in the study; answered a questionnaire, donated a blood sample. The antibodies to H. pylori were analysed by latex agglutination method. The baseline characteristics of study subjects with or without H. pylori infection were compared using the Chi-square test. Odds ratio (OR) and 95% confidence intervals (CI) for the association between H. pylori infection and potential risk factors were estimated using multivariable logistic regression models.

Results: Altogether 166 subjects (59% male; the median age - 51 years old) were included; 104 (62.7%) were H. pylori positive. There were no statistically significant differences between H. pylori positive and H. pylori negative groups in respect to the gender, anthropometric measurements, socioeconomic factors and personal habits. The multiple variable analysis showed that age (OR, 1.99; 95% CI, 1.03 - 3.86; P=0.04) and increased salt intake (OR, 2.21; 95% CI, 1.12 - 4.35; P=0.02) were associated with H. pylori infection.

Conclusions: More than half of the study subjects were infected with H. pylori in Kazakhstan. The prevalence of H. pylori infection was independently associated with older age and regular high salt consumption.
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http://dx.doi.org/10.31557/APJCP.2021.22.2.597DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8190350PMC
February 2021

Risk Factors for Non-Human Papillomavirus (HPV) Type 16/18 Cervical Infections and Associated Lesions Among HPV DNA-Negative Women Vaccinated Against HPV-16/18 in the Costa Rica Vaccine Trial.

J Infect Dis 2021 08;224(3):503-516

Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, Maryland, USA.

Background: Factors that lead human papillomavirus (HPV) infections to persist and progress to cancer are not fully understood. We evaluated co-factors for acquisition, persistence, and progression of non-HPV-16/18 infections among HPV-vaccinated women.

Methods: We analyzed 2153 women aged 18-25 years randomized to the HPV-vaccine arm of the Costa Rica HPV Vaccine Trial. Women were HPV DNA negative for all types at baseline and followed for approximately 11 years. Generalized estimating equation methods were used to account for correlated observations. Time-dependent factors evaluated were age, sexual behavior, marital status, hormonally related factors, number of full-term pregnancies (FTPs), smoking behavior, and baseline body mass index.

Results: A total of 1777 incident oncogenic non-HPV-16/18 infections were detected in 12 292 visits (average, 0.14 infections/visit). Age and sexual behavior-related variables were associated with oncogenic non-HPV-16/18 acquisition. Twenty-six percent of incident infections persisted for ≥1 year. None of the factors evaluated were statistically associated with persistence of oncogenic non-HPV-16/18 infections. Risk of progression to Cervical Intraepithelial Neoplasia grade 2 or worst (CIN2+) increased with increasing age (P for trend = .001), injectable contraceptive use (relative risk, 2.61 [95% confidence interval, 1.19-5.73] ever vs never), and increasing FTPs (P for trend = .034).

Conclusions: In a cohort of HPV-16/18-vaccinated women, age and sexual behavior variables are associated with acquisition of oncogenic non-HPV-16/18 infections; no notable factors are associated with persistence of acquired infections; and age, parity, and hormonally related exposures are associated with progression to CIN2+.
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http://dx.doi.org/10.1093/infdis/jiaa768DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8496490PMC
August 2021

Efficacy of the bivalent HPV vaccine against HPV 16/18-associated precancer: long-term follow-up results from the Costa Rica Vaccine Trial.

Lancet Oncol 2020 12;21(12):1643-1652

Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Rockville, MD, USA.

Background: Oncogenic human papillomavirus (HPV) infections cause most cases of cervical cancer. Here, we report long-term follow-up results for the Costa Rica Vaccine Trial (publicly funded and initiated before licensure of the HPV vaccines), with the aim of assessing the efficacy of the bivalent HPV vaccine for preventing HPV 16/18-associated cervical intraepithelial neoplasia grade 2 or worse (CIN2+).

Methods: Women aged 18-25 years were enrolled in a randomised, double-blind, controlled trial in Costa Rica, between June 28, 2004, and Dec 21, 2005, designed to assess the efficacy of a bivalent vaccine for the prevention of infection with HPV 16/18 and associated precancerous lesions at the cervix. Participants were randomly assigned (1:1) to receive an HPV 16/18 AS04-adjuvanted vaccine or control hepatitis A vaccine. Vaccines were administered intramuscularly in three 0·5 mL doses at 0, 1, and 6 months and participants were followed up annually for 4 years. After the blinded phase, women in the HPV vaccine group were invited to enrol in the long-term follow-up study, which extended follow-up for 7 additional years. The control group received HPV vaccine and was replaced with a new unvaccinated control group. Women were followed up every 2 years until year 11. Investigators and patients were aware of treatment allocation for the follow-up phase. At each visit, clinicians collected cervical cells from sexually active women for cytology and HPV testing. Women with abnormal cytology were referred to colposcopy, biopsy, and treatment as needed. Women with negative results at the last screening visit (year 11) exited the long-term follow-up study. The analytical cohort for vaccine efficacy included women who were HPV 16/18 DNA-negative at vaccination. The primary outcome of this analysis was defined as histopathologically confirmed CIN2+ or cervical intraepithelial neoplasia grade 3 or worse associated with HPV 16/18 cervical infection detected at colposcopy referral. We calculated vaccine efficacy by year and cumulatively. This long-term follow-up study is registered with ClinicalTrials.gov, NCT00867464.

Findings: 7466 women were enrolled in the Costa Rica Vaccine Trial; 3727 received the HPV vaccine and 3739 received the control vaccine. Between March 30, 2009, and July 5, 2012, 2635 women in the HPV vaccine group and 2836 women in the new unvaccinated control group were enrolled in the long-term follow-up study. 2635 women in the HPV vaccine group and 2677 women in the control group were included in the analysis cohort for years 0-4, and 2073 women from the HPV vaccine group and 2530 women from the new unvaccinated control group were included in the analysis cohort for years 7-11. Median follow-up time for the HPV group was 11·1 years (IQR 9·1-11·7), 4·6 years (4·3-5·3) for the original control group, and 6·2 years (5·5-6·9) for the new unvaccinated control group. At year 11, vaccine efficacy against incident HPV 16/18-associated CIN2+ was 100% (95% CI 89·2-100·0); 34 (1·5%) of 2233 unvaccinated women had a CIN2+ outcome compared with none of 1913 women in the HPV group. Cumulative vaccine efficacy against HPV 16/18-associated CIN2+ over the 11-year period was 97·4% (95% CI 88·0-99·6). Similar protection was observed against HPV 16/18-associated CIN3-specifically at year 11, vaccine efficacy was 100% (95% CI 78·8-100·0) and cumulative vaccine efficacy was 94·9% (73·7-99·4). During the long-term follow-up, no serious adverse events occurred that were deemed related to the HPV vaccine. The most common grade 3 or worse serious adverse events were pregnancy, puerperium, and perinatal conditions (in 255 [10%] of 2530 women in the unvaccinated control group and 201 [10%] of 2073 women in the HPV vaccine group). Four women in the unvaccinated control group and three in the HPV vaccine group died; no deaths were deemed to be related to the HPV vaccine.

Interpretation: The bivalent HPV vaccine has high efficacy against HPV 16/18-associated precancer for more than a decade after initial vaccination, supporting the notion that invasive cervical cancer is preventable.

Funding: US National Cancer Institute.
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http://dx.doi.org/10.1016/S1470-2045(20)30524-6DOI Listing
December 2020

Cognitions and behaviours of general practitioners in France regarding HPV vaccination: A theory-based systematic review.

Prev Med 2021 02 7;143:106323. Epub 2020 Nov 7.

Screening Group, Early Detection and Prevention Section, International Agency for Research on Cancer, World Health Organization (IARC - WHO), 69372 Lyon, France. Electronic address:

Human papillomavirus (HPV) vaccination is safe and efficacious to prevent persistent HPV infection, precancerous anogenital lesions and cervical cancer. However, in countries where vaccination programmes are implemented outside of schools, such as France, reaching high HPV vaccination coverage of the target population is challenging. Many studies have been performed in France to assess cognitions of general practitioners (GPs) regarding HPV vaccination. However, the evidence is not consistent about which cognitions are key. To provide a comprehensive overview, we performed a systematic review of studies conducted in France on GPs' cognitions regarding HPV vaccination and used the reasoned action approach to extract and synthesize data. The systematic search was performed up to July 2020 in Medline via PubMed, PsycINFO, PsycARTICLES, Embase, CINAHL Plus, Web of Science, Pascal and Francis databases. Grey literature was searched for in the French Public Health Database, Cairn. Info, yahoo.fr, and Google Scholar. Twenty-five scientific publications were selected based on eligibility criteria and assessed for quality. Our qualitative synthesis highlights that although 73% of GPs report recommending HPV vaccination, up to 50% would not recommend it because of concerns, including changes in patients' health behaviours and doubts about safety and/or efficacy. GPs' injunctive norms, i.e. trust in institutional information, were shown to be associated positively with GPs' willingness to recommend HPV vaccination. Parents' fears, girls' age, and potential connection with sexuality do not seem to affect GPs' recommendations. These results will inform the development of a professional educational intervention targeting GPs in France.
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http://dx.doi.org/10.1016/j.ypmed.2020.106323DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7840585PMC
February 2021

Does Family History of Cancer Influence Undergoing Screening and Gastrointestinal Investigations?

J Gastrointestin Liver Dis 2020 Oct 27;29(4):523-528. Epub 2020 Oct 27.

Faculty of Medicine, University of Latvia; Institute of Clinical and Preventive Medicine, University of Latvia, Riga, Latvia.

Background And Aims: Although a family history of cancer (FHC) can modify the lifestyle and attitudes towards participation in cancer screening programs, studies on this relationship show mixed results and vary across populations. The objectives of the study were to compare sociodemographic characteristics, history of gastrointestinal (GI) investigations and Helicobacter pylori eradication, and modifiable cancer risk factors between those with FHC and those with no FHC (NFHC), and to investigate the association between FHC and a history of GI investigations.

Methods: A total of 3,455 questionnaires from the pilot study of the "Helicobacter pylori eradication and pepsinogen testing for prevention of gastric cancer mortality (GISTAR study)" in Latvia were analysed. We compared sociodemographic characteristics and history of GI investigations between participants with self- reported FHC and NFHC. Binary logistic regression models adjusted for socio-demographic characteristics and modifiable cancer risk factors were built for a FHC and each GI investigation.

Results: Participants with a FHC were more likely to be women, have a higher education and less likely to have harmful habits (smoking, alcohol consumption) than those with NFHC. Participants with a FHC were approximately twice as likely to report recent colorectal investigations specifically for screening, than those with NFHC. In fully adjusted logistic regression models, FHC was significantly associated with a recent history of faecal occult blood tests (FOBTs), colonoscopies, and colorectal investigations (FOBT or colonoscopy) specifically for screening as part of the national organized screening programme.

Conclusion: Our results indicate that those with a FHC have different patterns of health-related behaviour than those with NFHC.
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http://dx.doi.org/10.15403/jgld-813DOI Listing
October 2020

Comparison of immediate colposcopy, repeat conventional cytology and hrHPV testing for the clinical management of ASC-US cytology in routine health services of Medellin, Colombia: The ASCUS-COL Trial.

Int J Cancer 2020 Oct 2. Epub 2020 Oct 2.

Group Infection and Cancer, School of Medicine, Universidad de Antioquia, Medellin, Colombia.

In the context of opportunistic cervical cancer screening settings of low-and-middle-income countries, little is known about the benefits of high-risk human papillomavirus (hrHPV) testing on high-grade cervical abnormality detection among women with atypical squamous cells of undetermined significance (ASC-US) cytology in routine clinical practice. We compared the effectiveness of immediate colposcopy (IC), conventional cytology at 6 and 12 months (colposcopy if ≥ASC-US) (RC), and hrHPV testing (colposcopy if hrHPV-positive) (HPV) to detect cervical intraepithelial neoplasia grade 2 or more severe diagnoses (CIN2+) among women aged 20-69 years with ASC-US in routine care. Participants (n=2,661) were evenly randomized into three arms (n=882 IC, n=890 RC, n=889 HPV) to receive services by routine healthcare providers and invited to an exit visit 24 months after recruitment. Histopathology was blindly reviewed by a quality-control external panel (QC). The primary endpoint was the first QC-diagnosed CIN2+ or CIN3+ detected during three periods: enrolment (≤6 months for IC and HPV, ≤12 months for RC), follow-up (between enrolment and exit visit), and exit visit. The trial is completed. Colposcopy was done on 88%, 42%, and 52% of participants in IC, RC, and HPV. Overall, 212 CIN2+ and 52 CIN3+ cases were diagnosed. No differences were observed for CIN2+ detection (p=0.821). However, compared to IC, only HPV significantly reduced CIN3+ cases that providers were unable to detect during the 2-year routine follow-up (relative proportion 0.35, 95% CI 0.09-0.87). In this context, hrHPV testing was the most effective and efficient management strategy for women with ASC-US cytology.
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http://dx.doi.org/10.1002/ijc.33318DOI Listing
October 2020

Sociodemographic, Lifestyle and Medical Factors Associated with Helicobacter Pylori Infection.

J Gastrointestin Liver Dis 2020 Sep 9;29(3):319-327. Epub 2020 Sep 9.

Faculty of Medicine, University of Latvia, Riga; Institute of Clinical and Preventive Medicine, University of Latvia, Riga, Latvia.

Background And Aims: The prevalence of Helicobacter pylori (H. pylori) infection is higher in developing countries and is often linked to lower socioeconomic status. Few studies have investigated the association between H. pylori and individual level characteristics in Europe, where several countries have a high prevalence of H. pylori infection. The study aimed to identify risk factors for H. pylori infection among adults in a large clinical trial in Latvia.

Methods: 1,855 participants (40-64 years) of the "Multicenter randomized study of H. pylori eradication and pepsinogen testing for prevention of gastric cancer mortality" (GISTAR study) in Latvia tested for H. pylori IgG antibodies were included in a cross-sectional analysis. Sociodemographic, lifestyle and medical factors were compared for participants seropositive (H. pylori+) and seronegative. Mutually adjusted odds ratios (OR) were calculated for H. pylori+ and factors significant in univariate analysis (education, smoking, binge drinking, several dietary habits, history of H. pylori eradication and disease), adjusting for age, gender and income.

Results: Of the participants 1,044 (55.4%) were H. pylori seropositive. The infection was associated with current (OR: 1.34, 95%CI: 1.01-1.78) and former (OR: 1.38; 95%CI: 1.03-1.85) smoking, binge drinking (OR: 1.35; 95%CI: 1.03-1.78), having ≥200g dairy daily (OR: 1.37; 95%CI: 1.11-1.69), and very hot food/drinks (OR: 1.32; 95%CI: 1.03-1.69) and inversely with ≥400g vegetables/fruit daily (OR: 0.76; 95%CI: 0.60-0.96), history of H. pylori eradication (OR: 0.57; 95%CI: 0.39-0.84), peptic ulcer (OR: 0.55; 95%CI: 0.38-0.80) and cardiovascular disease (OR: 0.78; 95%CI: 0.61-0.99).

Conclusions: After mutual adjustment, H. pylori seropositivity was associated with lifestyle and in particular dietary factors rather than socioeconomic indicators in contrast to the majority of other studies.
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http://dx.doi.org/10.15403/jgld-870DOI Listing
September 2020

Regional variations in Helicobacter pylori infection, gastric atrophy and gastric cancer risk: The ENIGMA study in Chile.

PLoS One 2020 8;15(9):e0237515. Epub 2020 Sep 8.

Public Health Department, School of Medicine, Pontificia Universidad Católica de Chile, Santiago, Chile.

Background: Regional variations in gastric cancer incidence are not explained by prevalence of Helicobacter pylori, the main cause of the disease, with several areas presenting high H. pylori prevalence but low gastric cancer incidence. The IARC worldwide H. pylori prevalence surveys (ENIGMA) aim at systematically describing age and sex-specific prevalence of H. pylori infection around the world and generating hypotheses to explain regional variations in gastric cancer risk.

Methods: We selected age- and sex-stratified population samples in two areas with different gastric cancer incidence and mortality in Chile: Antofagasta (lower rate) and Valdivia (higher rate). Participants were 1-69 years old and provided interviews and blood for anti-H. pylori antibodies (IgG, VacA, CagA, others) and atrophy biomarkers (pepsinogens).

Results: H. pylori seroprevalence (Age-standardized to world population) and antibodies against CagA and VacA were similar in both sites. H. pylori seroprevalence was 20% among children <10 years old, 40% among 10-19 year olds, 60% in the 20-29 year olds and close to or above 80% in those 30+ years. The comparison of the prevalence of known and potential H. pylori cofactors in gastric carcinogenesis between the high and the low risk area showed that consumption of chili products was significantly higher in Valdivia and daily non-green vegetable consumption was more common in Antofagasta. Pepsinogen levels suggestive of gastric atrophy were significantly more common and occurred at earlier ages in Valdivia, the higher risk area. In a multivariate model combining both study sites, age, chili consumption and CagA were the main risk factors for gastric atrophy.

Conclusions: The prevalence of H. pylori infection and its virulence factors was similar in the high and the low risk area, but atrophy was more common and occurred at younger ages in the higher risk area. Dietary factors could partly explain higher rates of atrophy and gastric cancer in Valdivia.

Impact: The ENIGMA study in Chile contributes to better understanding regional variations in gastric cancer incidence and provides essential information for public health interventions.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0237515PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7478833PMC
October 2020

Efficacy of AS04-Adjuvanted Vaccine Against Human Papillomavirus (HPV) Types 16 and 18 in Clearing Incident HPV Infections: Pooled Analysis of Data From the Costa Rica Vaccine Trial and the PATRICIA Study.

J Infect Dis 2021 May;223(9):1576-1581

Divison of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, Maryland, USA.

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.
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http://dx.doi.org/10.1093/infdis/jiaa561DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8248553PMC
May 2021

Reproducibility of a Rapid Human Papillomavirus Test at Different Levels of the Healthcare System in Tanzania: The AISHA Study.

Cancer Epidemiol Biomarkers Prev 2020 11 20;29(11):2261-2268. Epub 2020 Aug 20.

Department of Reproductive Health and Research, World Health Organization, Geneva, Switzerland.

Background: To inform policy makers in Tanzania if and how best to implement rapid HPV testing, we assessed the interobserver reproducibility of HPV test at three different levels of the healthcare system in an urban and a rural region of Tanzania.

Methods: Women aged 30 to 50 years were screened by HPV testing in two primary healthcare centers (PHC), two district hospitals (DiH), and two regional hospitals (ReH). Aliquots were retested at regional (ReH) and national referral laboratories (NRL). Reproducibility was evaluated using agreement and kappa index measures. Intralaboratory reproducibility was also evaluated in a set of 10 positive and 10 negative samples.

Results: Samples from 1,134 women were locally tested and retested at ReH and/or NRL. Test results from Dar es Salaam ReH and Kilimanjaro PHC showed clear quality problems including suspicion of contamination during testing or aliquoting. After excluding these samples, 18.8% of 743 women were HPV positive at clinic level. The resulting HPV reproducibility at different levels of the healthcare system was very good [agreement 95.7%, 95% confidence interval (CI), 94.0-96.9; kappa, 0.86, 95% CI, 0.81-0.91]. Intralaboratory agreement was also very good across four different experiments, with Fleiss' kappa between 0.87 (95% CI, 0.61-1.00) and 1.00 (0.75-1.00).

Conclusions: Rapid HPV testing was highly reproducible between lower and higher levels of the healthcare system in Tanzania; however, performance seems to be operator dependent.

Impact: The HPV test seems to be a feasible option for cervical cancer screening in an organized, decentralized system and in limited-resource settings if quality assurance measures are in place.
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http://dx.doi.org/10.1158/1055-9965.EPI-20-0422DOI Listing
November 2020

Alcohol drinking and head and neck cancer risk: the joint effect of intensity and duration.

Br J Cancer 2020 10 24;123(9):1456-1463. Epub 2020 Aug 24.

Institute of Oncology and Radiobiology, Havana, Cuba.

Background: Alcohol is a well-established risk factor for head and neck cancer (HNC). This study aims to explore the effect of alcohol intensity and duration, as joint continuous exposures, on HNC risk.

Methods: Data from 26 case-control studies in the INHANCE Consortium were used, including never and current drinkers who drunk ≤10 drinks/day for ≤54 years (24234 controls, 4085 oral cavity, 3359 oropharyngeal, 983 hypopharyngeal and 3340 laryngeal cancers). The dose-response relationship between the risk and the joint exposure to drinking intensity and duration was investigated through bivariate regression spline models, adjusting for potential confounders, including tobacco smoking.

Results: For all subsites, cancer risk steeply increased with increasing drinks/day, with no appreciable threshold effect at lower intensities. For each intensity level, the risk of oral cavity, hypopharyngeal and laryngeal cancers did not vary according to years of drinking, suggesting no effect of duration. For oropharyngeal cancer, the risk increased with durations up to 28 years, flattening thereafter. The risk peaked at the higher levels of intensity and duration for all subsites (odds ratio = 7.95 for oral cavity, 12.86 for oropharynx, 24.96 for hypopharynx and 6.60 for larynx).

Conclusions: Present results further encourage the reduction of alcohol intensity to mitigate HNC risk.
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http://dx.doi.org/10.1038/s41416-020-01031-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7592048PMC
October 2020

How do international gastric cancer prevention guidelines influence clinical practice globally?

Eur J Cancer Prev 2020 09;29(5):400-407

Technion, Israel Institute of Technology, Haifa, Israel.

Clinical guidelines recommend particular approaches, including 'screen-and-treat' strategy for Helicobacter pylori, to prevent gastric cancer. However, little of this is implemented in clinical practice. The aim of the study was to identify barriers to implementation of international guidelines. A web-based questionnaire distributed globally to specialists in the field. Altogether 886 responses from 75 countries were received. Of the responders, 570 (64%) were men of mean age 47 years. There were 606 gastroenterologists and 65 epidemiologists among the responders. Altogether, 79.8% of the responders disagreed that the burden of gastric cancer is a diminishing problem. 'Screen-and-treat' strategy for H. pylori in the responder's country was considered appropriate by 44.4%, inappropriate by 24.3%, with 31.3% being uncertain. Population-based screening for gastric cancer was considered appropriate in the respective home-country by 62.2%, in other areas - but not the home country - by 27.6%, and inappropriate by 10.2%. As a screening tool, upper endoscopy was acceptable by 35.6%, upper X-ray series by 55.3%, pepsinogens by 26.2% and breath-tests by 23.4%; accuracy, cost-effectiveness and feasibility among the tests varied widely. The attitude towards H. pylori vaccination was that 4.6% of the responders were eager to start vaccination immediately, 55.9% were supporting vaccination but considered that more data are required 12% were negative, and 27.6% did not have an opinion. In general, the attitude of the specialists was in line with guidelines, but was not always translated into clinical practice, particularly in the case of 'screen-and-treat' strategy.
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http://dx.doi.org/10.1097/CEJ.0000000000000580DOI Listing
September 2020

Evaluation of serological assays to monitor antibody responses to single-dose HPV vaccines.

Vaccine 2020 08 24;38(38):5997-6006. Epub 2020 Jul 24.

Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA. Electronic address:

Introduction: Whether existing serological assays are sufficiently robust to measure the lower antibody levels expected following single-dose HPV vaccination is unknown.

Methods: We evaluated seven assays measuring HPV-16/18 immunological responses overall and by number of doses in 530 serum samples from participants receiving varying doses of Cervarix or Gardasil up to 36-months post-vaccination. Serum was evaluated by simplex (HPV-16 ELISA, HPV-18 ELISA), multiplex (LIA-4, VLP-MIA, M9ELISA, GST-L1), and high-throughput pseudovirion-based neutralization assays (HT-PBNA), and results were compared to the gold standard HPV-16/18 secreted alkaline phosphatase neutralization assay (SEAP-NA). Reproducibility was assessed by the coefficient of variation (CV) and intraclass correlation coefficient (ICC). Percent agreement, Pearson correlation, and weighted-kappa were used to assess validity. Determinants of seronegativity were evaluated by chi-squared test.

Results: HPV-16: Seropositivity range was 97.1-99.5% for single dose and 98.8-99.8% overall. CV range was 4.0-18.0% for single dose and 2.9-19.5% overall. ICC range was 0.77-0.99 for single dose and 0.74-0.99 overall. Correlation with SEAP-NA range was 0.43-0.85 for single dose and 0.51-0.90 overall. Weighted-kappa range was 0.34-0.82 for single dose and 0.45-0.84 overall. HPV-18: Seropositivity range was 63.9-94.7% for single dose and 86.2-97.9% overall. CV range was 8.1-18.2% for single dose and 4.6-18.6% overall. ICC range was 0.75-0.99 for single dose and 0.83-0.99 overall. Correlation with SEAP-NA range was 0.31-0.99 for single dose and 0.27-0.96 overall. Weighted-kappa range was 0.35-0.83 for single dose and 0.45-0.84 overall. HPV-16 seronegativity was <5% for all assays. HPV-18 seronegativity range was 5.5-17.3%. For LIA-4 and GST-L1 where the proportion of seronegativity was >10%, the strongest correlates of seronegativity were receiving a single vaccine dose and receiving Gardasil.

Conclusions: These results support the utility of existing serological assays to monitor antibody responses following single-dose HPV vaccination.
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http://dx.doi.org/10.1016/j.vaccine.2020.07.017DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7429278PMC
August 2020

Multicentric study of cervical cancer screening with human papillomavirus testing and assessment of triage methods in Latin America: the ESTAMPA screening study protocol.

BMJ Open 2020 05 24;10(5):e035796. Epub 2020 May 24.

Instituto Nacional de Cancerología, Bogotá, Colombia.

Introduction: Human papillomavirus (HPV) testing is replacing cytology in primary screening. Its limited specificity demands using a second (triage) test to better identify women at high-risk of cervical disease. Cytology represents the immediate triage but its low sensitivity might hamper HPV testing sensitivity, particularly in low-income and middle-income countries (LMICs), where cytology performance has been suboptimal. The ESTAMPA (EStudio multicéntrico de TAMizaje y triaje de cáncer de cuello uterino con pruebas del virus del PApiloma humano; Spanish acronym) study will: (1) evaluate the performance of different triage techniques to detect cervical precancer and (2) inform on how to implement HPV-based screening programmes in LMIC.

Methods And Analysis: Women aged 30-64 years are screened with HPV testing and Pap across 12 study centres in Latin America. Screened positives have colposcopy with biopsy and treatment of lesions. Women with no evident disease are recalled 18 months later for another HPV test; those HPV-positive undergo colposcopy with biopsy and treatment as needed. Biological specimens are collected in different visits for triage testing, which is not used for clinical management. The study outcome is histological high-grade squamous intraepithelial or worse lesions (HSIL+) under the lower anogenital squamous terminology. About 50 000 women will be screened and 500 HSIL+ cases detected (at initial and 18 months screening). Performance measures (sensitivity, specificity and predictive values) of triage techniques to detect HSIL+ will be estimated and compared with adjustment by age and study centre.

Ethics And Dissemination: The study protocol has been approved by the Ethics Committee of the International Agency for Research on Cancer (IARC), of the Pan American Health Organisation (PAHO) and by those in each participating centre. A Data and Safety Monitoring Board (DSMB) has been established to monitor progress of the study, assure participant safety, advice on scientific conduct and analysis and suggest protocol improvements. Study findings will be published in peer-reviewed journals and presented at scientific meetings.

Trial Registration Number: NCT01881659.
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http://dx.doi.org/10.1136/bmjopen-2019-035796DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7252979PMC
May 2020

Psycho-social impact of positive human papillomavirus testing in Jujuy, Argentina results from the Psycho-Estampa study.

Prev Med Rep 2020 Jun 5;18:101070. Epub 2020 Mar 5.

Instituto Nacional de Cancerología, Calle 1 No.9-85, Bogotá, Colombia.

Human papillomavirus (HPV) testing can have a negative impact on women's lives which might also result in abandoning the follow-up and treatment process. This study measured the psycho-social impact of HPV-positivity among HPV-tested women from Jujuy, Argentina, a middle-low income setting. In this cross-sectional study (2015-2016), the psycho-social impact of HPV-positivity was measured using the Psycho-Estampa Scale, specifically designed and validated to be used in screening contexts. We measured mean scores for each of the five scale domains, and the Overall Impact score (Values from 1: No impact to 4: Heavy impact). We compared scores according to cytology triage diagnosis using ordinal logistic regression. A total of 163 HPV-positive women were recruited at the Centro Carlos Alvarado hospital and included in the study sample; of these, 124 (76.1%) had normal triage cytologies. The overall Impact score was between low and moderate (mean:2.56, SD:0.65). The highest psycho-social impact was measured in the Worries about cancer and treatment domain (mean score:3.60, SD:0.60), followed by Sexuality domain (mean:2.50; SD:1.00). The Uncertainty about information provided by health providers domain had the lowest mean score (mean:2.14, SD:0.73). Compared to women with normal cytologies (n = 124), women with abnormal cytologies (n = 39) had a higher likelihood of greater overall Psycho-social Impact (OR: 2.91; p = 0.0036). No statistically significant differences were found in scores of specific domains according to cytology results. It is important to devise specific counseling interventions to reduce the psycho-social impact of HPV-Testing as primary screening and its potential effect on completion of the diagnosis/ treatment process.
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http://dx.doi.org/10.1016/j.pmedr.2020.101070DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7113430PMC
June 2020

Cervicovaginal microbiome and natural history of HPV in a longitudinal study.

PLoS Pathog 2020 03 26;16(3):e1008376. Epub 2020 Mar 26.

Department of Pediatrics (Genetic Medicine), Albert Einstein College of Medicine, Bronx, New York, United States of America.

Background: Human papillomavirus (HPV) infection is one of the most common sexually transmitted infections. However, only a small percentage of high-risk (HR) HPV infections progress to cervical precancer and cancer. In this study, we investigated the role of the cervicovaginal microbiome (CVM) in the natural history of HR-HPV.

Methods: This study was nested within the placebo arm of the Costa Rica HPV Vaccine Trial that included women aged 18-25 years of age. Cervical samples from two visits of women with an incident HR-HPV infection (n = 273 women) were used to evaluate the prospective role of the CVM on the natural history of HR-HPV. We focus specifically on infection clearance, persistence, and progression to cervical intraepithelial neoplasia grade 2 and 3 (CIN2+). The CVM was characterized by amplification and sequencing the bacterial 16S V4 rRNA gene region and the fungal ITS1 region using an Illumina MiSeq platform. OTU clustering was performed using QIIME2. Functional groups were imputed using PICRUSt and statistical analyses were performed using R.

Results: At Visit 1 (V1) abundance of Lactobacillus iners was associated with clearance of incident HR-HPV infections (Linear Discriminant Analysis (LDA)>4.0), whereas V1 Gardnerella was the dominant biomarker for HR-HPV progression (LDA>4.0). At visit 2 (V2), increased microbial Shannon diversity was significantly associated with progression to CIN2+ (p = 0.027). Multivariate mediation analysis revealed that the positive association of V1 Gardnerella with CIN2+ progression was due to the increased cervicovaginal diversity at V2 (p = 0.040). A full multivariate model of key components of the CVM showed significant protective effects via V1 genus Lactobacillus, OR = 0.41 (0.22-0.79), V1 fungal diversity, OR = 0.90 (0.82-1.00) and V1 functional Cell Motility pathway, OR = 0.75 (0.62-0.92), whereas V2 bacterial diversity, OR = 1.19 (1.03-1.38) was shown to be predictive of progression to CIN2+.

Conclusion: This study demonstrates that features of the cervicovaginal microbiome are associated with HR-HPV progression in a prospective longitudinal cohort. The analyses indicated that the association of Gardnerella and progression to CIN2+ may actually be mediated by subsequent elevation of microbial diversity. Identified features of the microbiome associated with HR-HPV progression may be targets for therapeutic manipulation to prevent CIN2+.

Trial Registration: ClinicalTrials.gov NCT00128661.
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http://dx.doi.org/10.1371/journal.ppat.1008376DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7098574PMC
March 2020

Durability of Cross-Protection by Different Schedules of the Bivalent HPV Vaccine: The CVT Trial.

J Natl Cancer Inst 2020 10;112(10):1030-1037

Agencia Costarricense de Investigaciones Biomédicas, formerly Proyecto Epidemiológico Guanacaste, Fundación INCIENSA, San José, Costa Rica.

Background: The Costa Rica HPV Vaccine Trial has documented cross-protection of the bivalent HPV vaccine against HPV31/33/45 up to 7 years after vaccination, even with one dose of the vaccine. However, the durability of such protection remains unknown. Here, we evaluate the efficacy of different schedules of the vaccine against HPV31/33/45 out to 11 years postvaccination, expanding to other nontargeted HPV types.

Methods: We compared the rates of HPV infection in vaccinated women with the rates in a comparable cohort of unvaccinated women. We estimated the average vaccine efficacy (VEavg) against incident infections and tested for a change in VE over time.

Results: Among 3-dose women, we observed statistically significant cross-protection against HPV31/33/45 (VEavg = 64.4%, 95% confidence interval [CI] = 57.7% to 70.0%). Additionally, we observed borderline, statistically significant cross-protection against HPV35 (VEavg = 23.2%, 95% CI = 0.3% to 40.8%) and HPV58 (VEavg = 21.2%, 95% CI = 4.2% to 35.3%). There was no decrease in VE over time (two-sided Ptrend > .05 for HPV31, -33, -35, -45, and -58). As a benchmark, VEavg against HPV16/18 was 82.0% (95% CI = 77.3% to 85.7%). Among 1-dose women, we observed comparable efficacy against HPV31/33/45 (VEavg = 54.4%, 95% CI = 21.0% to 73.7%). Acquisition of nonprotected HPV types was similar between vaccinated and unvaccinated women, indicating that the difference in HPV infection rates was not attributable to differential genital HPV exposure.

Conclusions: Substantial cross-protection afforded by the bivalent vaccine against HPV31/33/45, and to a lesser extent, HPV35 and HPV58, was sustained and remained stable after 11 years postvaccination, reinforcing the notion that the bivalent vaccine is an effective option for protection against HPV-associated cancers.
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http://dx.doi.org/10.1093/jnci/djaa010DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7566371PMC
October 2020

Evaluation of Durability of a Single Dose of the Bivalent HPV Vaccine: The CVT Trial.

J Natl Cancer Inst 2020 10;112(10):1038-1046

HPV Immunology Laboratory, Leidos Biomedical Research, Inc., Frederick National Laboratory for Cancer Research, Frederick, MD, USA.

Background: The authors investigated the durability of vaccine efficacy (VE) against human papillomavirus (HPV)16 or 18 infections and antibody response among nonrandomly assigned women who received a single dose of the bivalent HPV vaccine compared with women who received multiple doses and unvaccinated women.

Methods: HPV infections were compared between HPV16 or 18-vaccinated women aged 18 to 25 years who received one (N = 112), two (N = 62), or three (N = 1365) doses, and age- and geography-matched unvaccinated women (N = 1783) in the long-term follow-up of the Costa Rica HPV Vaccine Trial. Cervical HPV infections were measured at two study visits, approximately 9 and 11 years after initial HPV vaccination, using National Cancer Institute next-generation sequencing TypeSeq1 assay. VE and 95% confidence intervals (CIs) were estimated. HPV16 or 18 antibody levels were measured in all one- and two-dose women, and a subset of three-dose women, using a virus-like particle-based enzyme-linked immunosorbent assay (n = 448).

Results: Median follow-up for the HPV-vaccinated group was 11.3 years (interquartile range = 10.9-11.7 years) and did not vary by dose group. VE against prevalent HPV16 or 18 infection was 80.2% (95% CI = 70.7% to 87.0%) among three-dose, 83.8% (95% CI = 19.5% to 99.2%) among two-dose, and 82.1% (95% CI = 40.2% to 97.0%) among single-dose women. HPV16 or 18 antibody levels did not qualitatively decline between years four and 11 regardless of the number of doses given, although one-dose titers continue to be statistically significantly lower compared with two- and three-dose titers.

Conclusion: More than a decade after HPV vaccination, single-dose VE against HPV16 or 18 infection remained high and HPV16 or 18 antibodies remained stable. A single dose of bivalent HPV vaccine may induce sufficiently durable protection that obviates the need for more doses.
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http://dx.doi.org/10.1093/jnci/djaa011DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7566548PMC
October 2020

Prevalence of Atrophic Gastritis in Kazakhstan and the Accuracy of Pepsinogen Tests to Detect Gastric Mucosal Atrophy.

Asian Pac J Cancer Prev 2019 12 1;20(12):3825-3829. Epub 2019 Dec 1.

Institute of Clinical and Preventive Medicine, University of Latvia, Riga, Latvia.

Background: Atrophic gastritis is considered precursor condition for gastric cancer. There is so far limited evidence on the performance of pepsinogens for atrophy detection in Central Asia. The aim of our study was to detect the prevalence of atrophic gastritis in the asymptomatic adult population in Kazakhstan as well as address the accuracy of pepsinogen testing in atrophy detection.

Methods: Healthy individuals aged 40-64 were included. Upper endoscopy and pepsinogens (PG) evaluation were performed. PG were analysed in plasma by latex agglutination. Cut off values were used to define decreased PG values (PGR ≤ 3 and PG I ≤ 70 ng/mL); severely decreased PG values (PGR ≤ 2 and PG I ≤ 30 ng/mL). Biopsies were analyzed and obtained according to the updated Sydney System. PG test sensitivity, specificity and overall accuracy were assessed using the histological diagnosis as the "gold standard".

Results: Altogether 157 individuals - female 40,1% and male 59,9% were included. Histologically, moderate to severe corpus atrophy, was present only in 1,3% cases. From all study subjects, 26,8% had decreased plasma PG values with cut-off values PGR ≤ 3 and PG I ≤ 70 ng/mL. The sensitivity of the PG test with this cut-off values was 50,0%, specificity 73,5%, overall accuracy 73,2% for detection of moderate to severe atrophy in the corpus. The sensitivity of PG test with cut-off values PGR ≤ 2 and PG I ≤30 ng/mL was 50,0%, specificity 90,9% and overall accuracy 90,4%.

Conclusions: The prevalence of gastric mucosal atrophy was low in the Kazakh population. Serological PG test screening nevertheless can play an important role in the diagnosis of gastric precancerous lesions. However, the diagnostic accuracy of the PG test is mainly dependent on the cut-off values for positive results.
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http://dx.doi.org/10.31557/APJCP.2019.20.12.3825DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7173362PMC
December 2019

Efficacy of the AS04-Adjuvanted HPV16/18 Vaccine: Pooled Analysis of the Costa Rica Vaccine and PATRICIA Randomized Controlled Trials.

J Natl Cancer Inst 2020 08;112(8):818-828

Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, MD.

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+.
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http://dx.doi.org/10.1093/jnci/djz222DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7825474PMC
August 2020

Population preferences for breast cancer screening policies: Discrete choice experiment in Belarus.

PLoS One 2019 1;14(11):e0224667. Epub 2019 Nov 1.

Duke Clinical Research Institute, Duke University, Durham, United States of America.

Background: Reaching an acceptable participation rate in screening programs is challenging. With the objective of supporting the Belarus government to implement mammography screening as a single intervention, we analyse the main determinants of breast cancer screening participation.

Methods: We developed a discrete choice experiment using a mixed research approach, comprising a literature review, in-depth interviews with key informants (n = 23), "think aloud" pilots (n = 10) and quantitative measurement of stated preferences for a representative sample of Belarus women (n = 428, 89% response rate). The choice data were analysed using a latent class logit model with four classes selected based on statistical (consistent Akaike information criterion) and interpretational considerations.

Results: Women in the sample were representative of all six geographic regions, mainly urban (81%), and high-education (31%) characteristics. Preferences of women in all four classes were primarily influenced by the perceived reliability of the test (sensitivity and screening method) and costs. Travel and waiting time were important components in the decision for 34% of women. Most women in Belarus preferred mammography screening to the existing clinical breast examination (90%). However, if the national screening program is restricted in capacity, this proportion of women will drop to 55%. Women in all four classes preferred combined screening (mammography with clinical breast examination) to single mammography. While this preference was stronger if lower test sensitivity was assumed, 28% of women consistently gave more importance to combined screening than to test sensitivity.

Conclusion: Women in Belarus were favourable to mammography screening. Population should be informed that there are no benefits of combined screening compared to single mammography. The results of this study are directly relevant to policy makers and help them targeting the screening population.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0224667PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6824571PMC
March 2020

Age at start of using tobacco on the risk of head and neck cancer: Pooled analysis in the International Head and Neck Cancer Epidemiology Consortium (INHANCE).

Cancer Epidemiol 2019 12 3;63:101615. Epub 2019 Oct 3.

Department of Clinical Sciences and Community Health, University of Milan, Milan, Italy.

Background: Tobacco use is a well-established risk factor for head and neck cancer (HNC). However, less is known about the potential impact of exposure to tobacco at an early age on HNC risk.

Methods: We analyzed individual-level data on ever tobacco smokers from 27 case-control studies (17,146 HNC cases and 17,449 controls) in the International Head and Neck Cancer Epidemiology (INHANCE) consortium. Adjusted odds ratios (ORs) and 95% confidence intervals (CIs) were estimated using random-effects logistic regression models.

Results: Without adjusting for tobacco packyears, we observed that younger age at starting tobacco use was associated with an increased HNC risk for ever smokers (OR: 1.64, 95% CI: 1.35, 1.97). However, the observed association between age at starting tobacco use and HNC risk became null after adjusting for tobacco packyears (OR: 0.97, 95% CI: 0.80, 1.19). In the stratified analyses on HNC subsites by tobacco packyears or years since quitting, no difference in the association between age at start and HNC risk was observed.

Conclusions: Results from this pooled analysis suggest that increased HNC risks observed with earlier age at starting tobacco smoking are largely due to longer duration and higher cumulative tobacco exposures.
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http://dx.doi.org/10.1016/j.canep.2019.101615DOI Listing
December 2019

Evaluation of TypeSeq, a Novel High-Throughput, Low-Cost, Next-Generation Sequencing-Based Assay for Detection of 51 Human Papillomavirus Genotypes.

J Infect Dis 2019 10;220(10):1609-1619

Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, Maryland.

Background: Human papillomaviruses (HPV) cause over 500 000 cervical cancers each year, most of which occur in low-resource settings. Human papillomavirus genotyping is important to study natural history and vaccine efficacy. We evaluated TypeSeq, a novel, next-generation, sequencing-based assay that detects 51 HPV genotypes, in 2 large international epidemiologic studies.

Methods: TypeSeq was evaluated in 2804 cervical specimens from the Study to Understand Cervical Cancer Endpoints and Early Determinants (SUCCEED) and in 2357 specimens from the Costa Rica Vaccine Trial (CVT). Positive agreement and risks of precancer for individual genotypes were calculated for TypeSeq in comparison to Linear Array (SUCCEED). In CVT, positive agreement and vaccine efficacy were calculated for TypeSeq and SPF10-LiPA.

Results: We observed high overall and positive agreement for most genotypes between TypeSeq and Linear Array in SUCCEED and SPF10-LiPA in CVT. There was no significant difference in risk of precancer between TypeSeq and Linear Array in SUCCEED or in estimates of vaccine efficacy between TypeSeq and SPF10-LiPA in CVT.

Conclusions: The agreement of TypeSeq with Linear Array and SPF10-LiPA, 2 well established standards for HPV genotyping, demonstrates its high accuracy. TypeSeq provides high-throughput, affordable HPV genotyping for world-wide studies of cervical precancer risk and of HPV vaccine efficacy.
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http://dx.doi.org/10.1093/infdis/jiz324DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6782103PMC
October 2019
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