Colorectal Cancer Screening by Fecal Immunochemical Tests (FIT): Considerations on Sampling and Markers (Hb and Hb/Hp Complex) of Fecal Occult Blood (FOB).

BACKGROUND/AIM: Formal demonstration of the efficacy of colorectal cancer (CRC) screening by fecal immunochemical tests (FITs) in reducing CRC incidence and mortality is still missing. The aim of this study was to analyze the impact of sampling and FIT marker in the recently implemented CRC screening program in Finland. PATIENTS AND METHODS: Because only the index test [FIT hemoglobin (Hb)]-positive subjects are verified by the reference test (colonoscopy), the new screening program is subject to verification bias that precludes estimating the diagnostic accuracy (DA) indicators. A previously published study (5) with 100% biopsy verification of colonoscopy referral subjects (called validation cohort, n=300) was used to derive these missing DA estimates. Two points of concern were addressed: i) only one-day sample tested, and ii) only the Hb component (but not Hb/Hp complex) was analyzed by FIT. RESULTS: The estimated DA of one-sample testing for Hb in the screening setting had a very low sensitivity (SE) (12.5%; 95%CI=12.3-12.7) for adenomas, with AUC=0.560 (for CRC, AUC=0.950). Testing three samples for Hb improved SE to 19.4% (95%CI=19.1-19.7%) but had little effect on overall DA (AUC=0.590). For adenomas, one-sample testing for Hb and Hb/Hp complex provided higher SE than three-sample testing for Hb (SE 20.6%; 95%CI=20.3-21.0), and the best SE was reached when two samples were tested for Hb and Hb/Hp complex (SE 47.5%; 95%CI=46.9-48.1%) (AUC=0.730). CONCLUSION: The strategy of the current CRC screening could be significantly improved by testing two consecutive samples by Hb and Hb/Hp complex, instead of stand-alone Hb testing of one sample.

Impact of Different Cofactors on Naturally Acquired Human Papillomavirus Antibody Levels Among Unvaccinated Pregnant Women.

Human papillomavirus (HPV) infections are common, transmitted by sexual and nonsexual routes. The present case-control setting was designed to examine potential cofactors associated with either persistently low or high HPV-antibody levels. The study subjects were from the Finnish HPV Family cohort of 329 baseline pregnant, non-HPV-vaccinated women, who were sampled for genital and oral HPV-DNA and HPV serology at baseline, and at 12, 24, and 36 months. Antibodies to the L1 major capsid protein of HPV 6, 11, 16, 18, and 45 were analyzed by multiplex HPV serology and HPV genotyping was performed. This study included 59 women, 23 women with persistently low (<200 median fluorescence intensity [MFI]) and 36 women with persistently high and always positive (>200 MFI) levels of these antibodies for all five HPV genotypes. Potential HPV-associated covariates were derived from detailed questionnaires. Only cofactors other than detected HPV genotype significantly impact on the levels of natural HPV antibodies. A higher number of past sexual partners or a history of diagnosed genital warts were significant covariates of high HPV antibody levels (p = 0.023 and p = 0.043, respectively). Of interest, women with a history of allergies presented with low levels of HPV antibodies (p = 0.03), potentially exposing these women to an increased risk of future HPV-related diseases that merit closer surveillance.

The Diagnostic Accuracy (DA) of ColonView Fecal Immunochemical Test (FIT) in Detecting Colorectal Adenoma (CRA) Can Be Improved by the Diagnostic Models (DM) that Include Triage and Risk Features of CRA.

BACKGROUND/AIM: This study assessed whether the diagnostic accuracy (DA) of ColonView (CV) fecal immunochemical test (FIT) in detecting colorectal adenoma (CRA) can be improved by the diagnostic models (DM) that include triage and risk features of CRA. PATIENTS AND METHODS: A total of 5,090 participants of colorectal neoplasia (CRN) screening were recruited prospectively between January 2014 and December 2016. The CRN cohort of 486 patients included 222 CRA patients and 264 non-CRA patients of whom three consecutive fecal samples were analyzed by two fecal occult blood (FOB) assays (CV FIT test, HemoccultSENSA test). Hierarchical multilevel logistic models were used to test the DA of CV test and DMs, visualised as hierarchical summary receiving operating characteristic (HSROC) curves. RESULTS: In conventional receiving operating characteristic (ROC) analysis, the area under the curve (AUC) values of the age, height, weight, and body mass index (BMI) were 0.60, 0.57, 0.54, and 0.51, respectively. The AUC values for different DMs ranged from 0.69 (for DM without triage I/II and SENSA), and the highest AUC value of 0.70 was reached for DM with all variables included. In HSROC analysis, the AUC values for i) lowR variables, ii) highR variables, and ii) DMs were as follows: i) AUC=0.506, ii) AUC=0.566 and iii) AUC=0.732. The differences in AUC values were: between i) and ii) p=0.008; between i) and iii) p<0.0001; between ii) and iii) p<0.0001. CONCLUSION: The results demonstrated that DMs, particularly those including risk factors, significantly improved the DA of the CV FIT test in detecting CRA compared to traditional low-risk (lowR) and high-risk (highR) features alone. This study provides novel evidence supporting the enhanced diagnostic performance of DMs in combination with CV FIT testing for the detection of CRA.

Awareness and Acceptance of Nicotine-free Smoking Intervention Methods (Acetium® Lozenge) Increased Among Health Care Professionals by Targeted E-training as Confirmed by Post-training Surveys.

BACKGROUND/AIM: To increase the awareness and acceptance of the new nicotine-free smoking intervention method (Acetium® lozenge; Biohit Oyj, Finland), targeted E-Training with accompanying surveys were conducted in 2018, 2020 and 2023. PATIENTS AND METHODS: The target groups were derived from the General Data Protection Regulation (GDPR)-compliant registers of Finnish physicians, pharmacy staff and nurses owned by Success Clinic Oy. The post-training surveys recorded 1) awareness of the responders on Acetium® lozenge, 2) their attitude to nicotine-free smoking intervention methods in general as well as 3) their readiness for recommending this new tool to their patients. RESULTS: The three surveys accumulated a total of 1.892 responders. There was a constantly increasing awareness on Acetium® lozenge, increased interest in nicotine-free smoking intervention methods in general and a substantially increased readiness to recommend Acetium® acceptance to the smoking patients. The impact of E-Training, as measured by the increased interest in nicotine-free methods (56%) and readiness to endorse Acetium® acceptance (58%), was most marked among nurses who had the least awareness on Acetium® lozenge beforehand, exceeding the respective increase among medical doctors by 20% and 10% and among pharmacy staff by 30% and 20%, respectively. CONCLUSION: This E-Training had a favorable effect 1) on the responders' interest in nicotine-free smoking intervention method in general, 2) on increasing the awareness of Acetium® lozenge as a novel innovative method to quit smoking, as well as 3) on increasing the responders' readiness to introduce the new device to their smoking patients who are motivated to stop smoking nicotine-free.

Triage Process at Endoscopy With ColonView Fecal Immunochemical Test (FIT) Will Enhance Diagnostic Accuracy (DA) of Colorectal Cancer Screening.

BACKGROUND/AIM: This study assessed the diagnostic accuracy (DA) of the predictive features of colorectal cancer (CRC, predictCRC), triage process (triage), and ColonView (CV) fecal immunochemical test (FIT) in a CRC screening setting. The diagnostic score models (DMs) including predictCRC with triage and CV test were also calculated. PATIENTS AND METHODS: The study cohort of 544 patients included 58 CRC patients and 486 non-CRC patients who submitted three consecutive fecal samples for analysis, by two fecal occult blood (FOB) assays (CV FIT test, HemoccultSENSA test). Hierarchical multilevel logistic models were used to test the DA (for CRC) of each item of predictCRC (with triage I and II) and DMs, visualized as hierarchical summary receiving operating characteristic (HSROC) curves. RESULTS: The DA of the predictCRC location of neoplasm (Loc), triage I, and triage II showed 49%, 41%, and 93% sensitivity (Se), and 70%, 99.5%, and 88% specificity (Sp), respectively. The PPV+ of triage I (92%) was higher than that of Loc (22%) or triage II test (45%). In the conventional receiver operating characteristic (ROC) analysis, the area under the curve (AUC) values for the different DMs ranged from 0.880 (for DM without triage I and II), whereas the highest AUC value of 0.960 was reached for DM with triage I and II included in the formula. In the HSROC analysis, the AUC values were as follows: i) with all predictCRCs, AUC=0.717 and ii) with DMs, AUC=0.937. In the roccomp analysis, the difference in AUC values between i) and ii) was statistically significant (p<0.0001). CONCLUSION: In the detection of CRC, the DA of the new DMs with triage was far superior to that of DMs without triage. This is the first study to report evidence of improved DA in the detection of CRC using DMs including predictCRC with triage and CV FIT test.

Effect of a Second Pregnancy on the HPV Serology in Mothers Followed Up in the Finnish Family HPV Study.

The impact of pregnancy on human papillomavirus (HPV) natural antibody levels is not fully understood. We tested the seroprevalence and levels of HPV 6, 11, 16, 18 and 45 antibodies at different time points among 89 women with a second pregnancy and 238 nonpregnant women during their 36-month followup. All participants were unvaccinated for HPV and pregnant at the enrollment of the study. Serum samples were collected from the mothers at baseline and at the 12-month, 24-month, and 36-month followup visits. No statistically significant differences in mean antibody levels were observed in women who developed a second pregnancy compared to their nonpregnant counterparts. Between these two groups, statistically significant differences in serostatus were observed, particularly if the second pregnancy was ongoing at the 24-month timepoint. Accordingly, women with a second pregnancy were more likely to be seronegative for HPV 6, 11, 18, and 45 as compared to the nonpregnant women, the reverse being true for HPV16. In contrast, the women with an ongoing second pregnancy showed a higher prevalence of HPV16 seropositivity at the 36-month followup. These data suggest that a second pregnancy does not seem to have a major impact on the levels of HPV antibodies, but it might influence the serological outcomes.

IgG Seroreactivites to Viral Capsid Protein VP1 of JC and BK Polyomaviruses in Children at Early Ages with Special Reference to Parental Cofactors.

BK (BKPyV) and JC (JCPyV) polyomaviruses are widespread in humans. Transmission at an early age and the role of parents in spreading these viruses through the family are incompletely understood. Our aim was to determine the seroprevalence of BKPyV and JCPyV in infants at the age of 1, 2, 6, 12, 24, and 36 months and to assess the frequency of BKPyV and JCPyV seroconversion. A variety of maternal and paternal covariates were also tested as potential predictors of these early childhood infections. We used multiplex serology to analyze antibodies to BKPyV and JCPyV from baseline to 3-year follow-up visits. We observed that there was nearly perfect correlation in BKPyV and JCPyV serum IgG antibody levels between the mother-infant pairs during the first year of the infant's life. No correlation among BKPyV antibody titers were found in father-child pairs, whereas JCPyV antibody levels of the father and child had a significant correlation at the 2-year follow-up visit. BKPyV infection may be associated with a child's predisposition to allergy. In conclusion, after the decay of maternal antibodies, children start to develop their own immunity toward BKPyV and JCPyV, and horizontal transmission of infection in the family can occur.

Accuracy of Prediction Models in Diagnosis of Acute Diverticulitis.

BACKGROUND/AIM: The diagnostic score models (DMs) for patients with acute diverticulitis (AcDi) have been rarely evaluated. Therefore, we tried to develop diagnostic models (DMs) to enhance the diagnostic accuracy (DA) of AcDi. PATIENTS AND METHODS: In this AAP (acute abdominal pain) cohort, 30 AcDi patients were compared to 1,303 non-AcDi patients, with regard to their i) clinical symptoms (n=22), ii) signs and tests (n=14) as well as iii) laboratory analyses (n=3). The triage was performed at patient arrival to the emergency department (ED) (triage I) and at follow-up (triage II) before final decision. The triage included a suggested diagnosis of the AAP patient. Bivariate random effects meta-analysis was performed separately for 1) the pooled symptoms (n=22), 2) signs & tests (n=17) as well as 3) pooled DMs (I-V) with different cut-offs (with or without triage) to assess the diagnostic accuracy (DA) in detection of AcDi by HSROC (hierarchical summary receiver operating characteristic) curves. RESULTS: In the conventional receiver operating characteristic (ROC) analysis (for test optimization and finding optimal cut-off points), the area under curve (AUC) reached the following values for AcDi: i) DM without triage, AUC=0.843, ii) DM with triage I, AUC=0.866 and iii) DM with triage I and II, AUC=0.926. In the HSROC analysis, the AUC values for detection of AcDi were as follows; i) pooled clinical symptoms, AUC=0.540, ii) pooled clinical signs & tests, AUC=0.556 and iii) pooled DMs globally, AUC=0.853. In roccomp analysis for differences in AUC values: i) and iii) p<0.0001; between ii) and iii) p<0.0001. CONCLUSION: As confirmed by ROC and HSROC analysis, the new DMs with triage mode proved to be far superior in their DA for AcDi as compared to both symptoms and signs & tests. In the lack of earlier studies, these data report the first evidence that the DM including triage at an ED could improve the detection of AcDi.

HLA-G Alleles Impact the Perinatal Father-Child HPV Transmission.

The host factors that influence father-to-child human papillomavirus (HPV) transmission remain unknown. This study evaluated whether human leukocyte antigen (HLA)-G alleles are important in father-to-child HPV transmission during the perinatal period. Altogether, 134 father-newborn pairs from the Finnish Family HPV Study were included. Oral, semen and urethral samples from the fathers were collected before the delivery, and oral samples were collected from their offspring at delivery and postpartum on day 3 and during 1-, 2- and 6-month follow-up visits. HLA-G alleles were tested by direct sequencing. Unconditional logistic regression was used to determine the association of the father-child HLA-G allele and genotype concordance with the father-child HPV prevalence and concordance at birth and during follow-up. HLA-G allele G*01:01:03 concordance was associated with the father's urethral and child's oral high-risk (HR)-HPV concordance at birth (OR 17.00, 95% CI: 1.24-232.22). HLA-G allele G*01:04:01 concordance increased the father's oral and child's postpartum oral any- and HR-HPV concordance with an OR value of 7.50 (95% CI: 1.47-38.16) and OR value of 7.78 (95% CI: 1.38-43.85), respectively. There was no association between different HLA-G genotypes and HPV concordance among the father-child pairs at birth or postpartum. To conclude, the HLA-G allele concordance appears to impact the HPV transmission between the father and his offspring.

Fecal Immunochemical Test (FIT) in Triage of Bleed-positive (Crab+) and Bleed-negative Colorectal Adenoma (Crab-) Patients in Colorectal Neoplasia Screening.

BACKGROUND/AIM: Fecal immunochemical tests (FITs) are sensitive and specific for detecting colorectal cancer (CRC), but their diagnostic accuracy (DA) in bleed-positive (CRAb+) and bleed-negative colorectal adenomas (CRAb-) has been rarely tested. PATIENTS AND METHODS: A total of n=506 patients were included in the study, each collecting 3 consecutive stool samples for analysis. The stool samples were analyzed by the ColonView FIT (CV) and Hemoccult SENSA tests. A total of 484/5,090 (9.5%) patients returned all 3 samples and were subjected to final analysis. Hierarchical summary receiver operating characteristic (HSROC) analysis with different cut-offs for hemoglobin/haptoglobin (Hb and Hb/Hp) complex was performed to assess the DA of CV. RESULTS: In the HSROC analysis, the AUC values were as follows: i) bleed-positive adenoma patients by visual analysis mode (VA), AUC=0.566, ii) bleed-positive adenoma patients by automatic analysis mode (AA), AUC=0.546, iii) bleed-negative adenoma patients by VA, AUC=0.534 and iv) bleed-negative adenoma patients by AA, AUC=0.589: In roccomp analysis, there were significant differences in AUC values between iii) and iv) p=0.045. CONCLUSION: When stratified by the 'blood in stool' (as b+ or b- endpoint), the DA of the CV test is quite similar for CRAb+ and CRAb-. However, of the two modes (VA/AA) of the CV test, the AA reading gives a slightly higher DA both CRAb+ and CRAb-.

Human polyomavirus BKPyV and JCPyV serostatus has no impact on women´s human papillomavirus infection outcome.

Introduction: Polyomaviruses have both structural and functional similarities with papillomaviruses. Accordingly, their role in human papillomavirus (HPV) associated malignancies has been studied with conflicting results. Our goal was to disclose any association between BK (BKPyV) and/or JC (JCPyV) polyomavirus serology and HPV data derived from Finnish women (327) in a 6-year prospective follow-up. Methods: Glutathione S-transferase fusion-protein-capture (ELISA) in combination with fluorescent bead technology was used to analyze antibodies to BKPyV and JCPyV. In the longitudinal setting, BKPyV or JCPyV serostatus was related to i) oral- and ii) genital low (LR)- and high risk (HR) HPV DNA detection, iii) HPV16 persistence at both these sites, iv) results of the Pap (Papanicolaou) smear taken at baseline, and v) development of incident CIN (cervical intraepithelial neoplasia) during the follow-up. Results: Being BKPyV or JCPyV seropositive was not significantly associated with HPV seropositivity to either LR- or HR-genotypes, genital- or oral HPV DNA positivity, persistence of genital- or oral HPV16 infection, grade of Pap smear, or development of incident CIN. Discussion: Thus, the present study could not provide any confirmation to the concept that co-infections by HPyV and HPV have interactions that impact on the clinical manifestations or outcomes of HPV infections either in the genital tract or in the oral mucosa.

Diagnostic Accuracy of Fecal Immunochemical Test (FIT) in Bleed-positive and Bleed-negative Colorectal Cancer (CRC) Among a Cohort of 5,090 Subjects who Participated in the Colorectal Neoplasia (CRN) Screening in Brazil.

BACKGROUND/AIM: This study assessed the diagnostic accuracy (DA) of fecal immunochemical test (FIT) ColonView (CV) and guaiac-based fecal occult blood test (HemoccultSENSA) among bleed-positive (history or signs of intestinal bleeding) and bleed-negative participants (no history or signs of intestinal bleeding) (n=5,090) in colorectal neoplasia (CRN) screening in Brazil. PATIENTS AND METHODS: The eligible patients for the study (n=506) collected three consecutive stool samples, to be analyzed by both assays (CV, SENSA). Finally, 421/5090 (8.3%) patients returned both samples, which were subjected to final analysis. Receiver operating characteristic (ROC) analysis with different cut-offs was performed to assess the DA. RESULTS: The area under curve (AUC) values for i) visually analyzed (VA) CV for bleed-positive CRC, ii) automatically analyzed (AA) CV for bleed-positive CRC, iii) VA CV for bleed-negative CRC, and iv) AA CV for bleed-negative CRC as endpoints were as follows: i) AUC=0.864, ii) AUC=0.933, iii) AUC=0.836, and iv) AUC=0.892. In roccomp analysis, the differences in AUC values were: between i) and ii) p=0.068; between i) and iii) p=0.497; between i) and iv) p=0.488; between ii) and iii) p=0.0058; between ii) and iv) p=0.229; and between iii) and iv) p=0.138. CONCLUSION: This is the first investigation where two modes of CV test, VA, and AA, for bleed-positive and bleed-negative CRC patients were used as the endpoint. The AA reading of the CV test showed higher DA in bleed-positive than in bleed-negative CRC patients.

Seroprevalence of polyomaviruses BK and JC in Finnish women and their spouses followed-up for three years.

BK (BKPyV) and JC (JCPyV) polyomavirus infections are commonly subclinical and known infrequently to cause serious clinical diseases. Longitudinal follow-up studies regarding JCPyV and BKPyV serological outcomes are scanty. We analyzed JCPyV and BKPyV IgG-antibodies in 327 pregnant women and their 132 spouses, enrolled in the longitudinal Finnish Family HPV cohort at Turku University Hospital, Finland. Blood samples taken at baseline, and at 12-, 24-, and 36-month follow-up visits were analyzed for capsid protein VP1-antibodies using multiplex serology. Seroprevalence was constant for both BKPyV and JCPyV across the follow-up, varying between 95-99% and 59-68%, respectively, in women and between 96-97% and 66-72%, respectively, in their spouses. Seroconversion to BKPyV and JCPyV was detected in 15% and 18% of the women and in 13% and 19% of the men, respectively. Waning of BKPyV and JCPyV antibodies was infrequent, present in only 5% of the women (both viruses) and in 1.5% of the male spouses (only BKPyV). The number of lifetime sexual partners (p = 0.038) was lower among JCPyV seropositive men. To conclude, seropositivity to BKPyV and JCPyV is common among marital couples in Finland, with only slight differences between genders. In men, the sexual behavior might be associated with JCPyV seroprevalence.

Peripheral Blood T-lymphocyte Phenotypes in Mother-Child Pairs Stratified by the Maternal HPV Status: Persistent HPV16 vs. HPV-Negative: A Case-Control Study.

Only few studies exist on the phenotype distribution of peripheral blood lymphocytes concerning persistent oral HPV infection. T-lymphocyte subsets were phenotyped in women who had persistent genital or oral HPV16 infection, using HPV-negative women as a reference group. A subset of 42 mothers and their children (n = 28), were stratified into two groups according to the mothers' HPV status. PBMCs from previously cryopreserved venous samples were immunophenotyped by flow cytometry. Proportions of the CD4+ or CD8+ lymphocytes by their immunophenotype subsets were compared between HPV-positive and -negative mothers and their children. The mean rank distribution of CD8+ memory cells was significantly higher among mothers with persistent genital HPV16 infection. The median levels of both the antigen-presenting CD4+ cells and activated CD8+ cells were significantly lower in mothers with persistent oral HPV16 infection. When oral and genital HPV16-persistors were analyzed as a group, a marker of terminal effector cells was significantly increased as compared to HPV-negative women. Significantly higher levels of activated CD4+, CD8+ and circulating CD8+ memory cells were found among children whose mothers had persistent oral HPV16 infection. Persistent HPV16 infections are associated with changes in peripheral blood T-lymphocyte subsets. The mother's persistent oral HPV16 infection possibly results in immune alterations in her offspring.

A Simple Prediction Score for Diagnosis of Acute Pancreatitis.

BACKGROUND/AIM: The diagnostic accuracy (DA) for patients with acute pancreatitis (AcPa) has been rarely evaluated. PATIENTS AND METHODS: In the AcPa study group, there were 22 patients versus 1,311 patients in the non-AcPa group. The clinical history-taking variables (CHT) (n=22), clinical signs & tests details (CST) (n=14), and laboratory analyses (n=3) were recorded in each patient. Meta-analytical techniques were used to detect the summary sensitivity (Se) and specificity (Sp) estimates for each data set; CHT, CST, and diagnostic scores (DS). RESULTS: In receiver operating characteristic (ROC) analysis, the area under curve (AUC) values for i) CHT, ii) CST, and iii) DS were as follows: i) AUC=0.640 (95%CI=0.550-0.730); ii) AUC=0.588 (95%CI=0.520-0.656), and iii) AUC=0.943 (95%CI=0.910-0.976). The differences between these AUC values (roccomp analysis) are as follows: i) versus ii) p=0.155; i) versus iii) p<0.0001; ii) versus iii) p<0.0001. CONCLUSION: The new DS introduced in this study proved to be far superior to both symptoms and signs & tests in its DA for AcPa, as demonstrated by HSROC analysis.

Site-specific Performance of ColonView (CV) Fecal Immunochemical Test (FIT) With Differences Between Proximal and Distal Colorectal Adenoma.

BACKGROUND/AIM: The aim of this study was to assess the diagnostic accuracy (DA) of a ColonView (CV) test in proximal versus distal colorectal adenoma (pCRA versus dCRA). PATIENTS AND METHODS: The colorectal neoplasia (CRN) screening cohort included 5,090 individuals and 506/5,090 (10%) were eligible for the study. Finally, only 127/506 were included in the CRA analysis and hierarchical summary ROC (HSROC) curves were used to show the pooled overall DA of visually analyzed (VA) and automatically analyzed (AA) techniques in pCRA and dCRA detection. RESULTS: The overall specificity (Sp) of the AA technique for the pCRA and dCRA endpoint was 46% and 43%, respectively. The most sensitive AA test in pCRA patients showed 76% sensitivity (Se) versus 58% Se in dCRA patients. In the HSROC analysis, area under the curve (AUC) values were as follows: i) VA in pCRA: AUC=0.503, ii) AA in pCRA: AUC=0.560, iii) VA in dCRA: AUC=0.552 and iv) AA in dCRA: AUC=0.486. In Roccomp analysis, the statistically significant AUC values were available between VA and AA reading modes in pCRA (p=0.044) and in AA reading between pCRA and dCRA (p=0.024). CONCLUSION: As compared with the CRC endpoint, the DA value of the CV test is far inferior for the CRA endpoint, as determined by the AUC values.

Somatic targeted mutation profiling of colorectal cancer precursor lesions.

BACKGROUND: Most colorectal cancers (CRC) arise from precursor lesions. This study aimed to characterize the mutation profile of colorectal cancer precursor lesions in a Brazilian population. METHODS: In total, 90 formalin-fixed paraffin-embedded colorectal precursor lesions, including 67 adenomas, 7 sessile serrated lesions, and 16 hyperplastic polyps, were analyzed by next-generation sequencing using a panel of 50 oncogenes and tumor suppressor genes. The genetic ancestry of the patients was estimated. RESULTS: Somatic driver mutations were identified in 66.7% of cases, including alterations in APC (32.2%), TP53 (20.0%), KRAS (18.9%), BRAF (13.3%) and EGFR (7.8%). Adenomas displayed a higher number of mutations, mainly in APC, compared to serrated polyps (73.1% vs. 47.8%, p = 0.026). Advanced adenomas had a significantly higher frequency of mutation in KRAS and a high overall mutation rate than early adenomas (92.9% vs. 59%, p = 0.006). A high degree of ancestry admixture was observed in the population studied, with a predominance of European components (mean of 73%) followed by African (mean of 11.3%). No association between genetic ancestry and type of lesions was found. The mutation profile of Brazilian colorectal precursor lesions exhibits alteration in APC, KRAS, TP53, and BRAF at different frequencies according to lesion type. CONCLUSIONS: These results bestow the knowledge of CRC's biologic history and support the potential of these biomarkers for precursor lesions detection in CRC screening of the Brazilian population.

Outcomes of HPV type-specific serostatus do not associate with oral or genital HPV-carriage in non-vaccinated women followed for three years.

BACKGROUND: The role of human papillomavirus (HPV) antibodies acquired through natural infection and their role in protection for subsequent cervical or oral HPV-carriage remains unclear. METHODS: A total of 267 women, with a 36-months follow-up, from the Finnish Family HPV (FFHPV) study were evaluated to shed more light on persistent HPV-specific antibodies to genital or oral HPV-carriage, clearance or persistence during the three years follow-up. The type-specific seroprevalence for HPV genotypes 6, 11, 16, 18 and 45 in these women was assessed in relation to the detection of the same genotype or any HPV in their oral and genital samples. The following HPV serological outcomes where detected: being always seronegative, seroconversion or persistent seropositivity. RESULTS: Genital HPV16 infections were most prevalent at the end of the follow-up (24- and 36-month visit) among women who tested always seronegative for HPV16. No such associations between serology and HPV detection were established for the other HPV genotypes in the genital or oral samples. The development of long-term type-specific HPV 6,11,16,18 and 45 persistence (≥ 24 months) or clearance of the genital or oral infections was not different among the women with high HPV genotype specific antibody levels and those testing always HPV-seronegative. CONCLUSION: No significant role was disclosed for the acquired natural high-level- or persistent HPV antibodies as determinants of the genital or oral HPV infection outcomes in these young, non-vaccinated women.

Accuracy of Serum Biomarker Panel (GastroPanel®) in the Diagnosis of Atrophic Gastritis of the Corpus. Systematic Review and Meta-analysis.

BACKGROUND/AIM: The serological biomarker panel (GastroPanel®)(GP) developed by Biohit Oyj (Helsinki, Finland) has gained increasing global acceptance in the diagnosis of atrophic gastritis (AG). This is a systematic review and meta-analysis of the studies on diagnostic accuracy of GP (GPA). MATERIALS AND METHODS: Core electronic databases were searched until the end of December 2021, following the principles of the PRISMA-P and using the QUADAS-2 quality assessment tool. STATA software with relevant packages (metandi, midas, mylabels) was used for meta-analysis, with AG of the corpus (AGC) as the endpoint. Summary estimates of Se and Sp, LR+ and LR- were calculated using random effect bivariate model (Forest plots), and summary receiver operating characteristic (SROC) curves by hierarchical SROC (HSROC) model. RESULTS: Altogether, 49 studies were found eligible, comprising 22,597 patients examined by the GP test. Significant heterogeneity across the studies was confirmed in Forest plots, HSROC and bivariate boxplot. The pooled Se of GP in diagnosis of AGC was 0.70 (95%CI=0.64-0.76) and pooled Sp was 0.93 (95%CI=0.90-0.95), with AUC=0.900 (95%CI=0.170-1.000) in HSROC. In Fagan's nomogram, positive GP test predicts AGC at population level with the likelihood of 72%. Meta-regression and subgroup meta-analysis disclosed publication year (<2008>) as the only significant source of heterogeneity, geographic origin of the study being of borderline significance. CONCLUSION: These meta-analytical results confirm the accuracy of GastroPanel® test in the diagnosis of AGC, advocating its applicability i) in screening for gastric cancer risk conditions (AG, Helicobacter pylori), as well as ii) in non-invasive diagnosis of dyspeptic patients, and iii) in follow-up of AG-patients.