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Populations of two eastern countries of Japan and Korea and with a related history share a predominant genotype of herpes simplex virus type 1.

Herpes simplex virus type 1 (HSV-1), a common human pathogen of non-epidemic nature is linked closely to the individual by latent infection. HSV-1 genotypes usually differ with race. Based on a "dual structure model" for population history of the Japanese, modern Japanese populations are assumed to have derived from two major migration events. The Jomon people arrived in Japan > 10,000 years ago and the Yayoi people began migrating to Japan from the Korean peninsula approximately 2,300 years ago. The presence of two predominant genotypes of F1 and F35 was noted in HSV-1 strains isolated in Japan. As the F1 genotype also predominated in Korea, peoples of Japan and Korea share the F1 genotype. Regional differences in the frequency of F1 and F35 genotypes within Japan seem to relate to differences in the dispersion of descendants of the Yayoi and Jomon peoples. Our hypothesis is that the F35 genotype relates to the Jomon people, earlier residents in japan, while the F1 genotype relates to the Yayoi people who migrated much later from the Korean peninsula.

China↗

Hepatitis B virus genotypes in Mongols and Australian Aborigines.

Hepatitis B virus (HBV) is spread worldwide. Seven genotypes, A-G, have been described, differing by more than 8% of the genome. In eastern Asia and Oceania genotypes B and C are predominant. However, little is known about genotypes in Mongolia and Australian aborigines. We analysed the preS and S regions of HBV from 9 Mongols and 5 Australian Aborigines. All Mongolian strains were of genotype D and were most similar to Central Asian sequences. All the Australian strains were genetically of serotype ayw3, and could not be reliably classified by the S region analysis, but placed on a separate branch. By preS analysis, they were however clearly of genotype C. The 6-7% nucleotide difference from published Asian genotype C sequences suggests that they diverged from Asian genotype C branch more than 1000 years ago.

Asian People↗

Vitamin D and estrogen receptor-alpha genotype and indices of bone mass and bone turnover in Danish girls.

Peak bone mass is a major determinant of osteoporosis risk in later life. It is under strong genetic control; however, little is known about the identity of the genes involved. In the present study, we investigated the relationship between polymorphisms in the genes encoding the vitamin D receptor (VDR) (FokI, TaqI) and estrogen receptor-alpha (ERalpha) (PvuII, XbaI), and bone mineral density (BMD), bone mineral content (BMC), and markers of bone turnover in 224 Danish girls aged 11-12 years. BMD and BMC were measured by dual-energy X-ray absorptiometry. Serum osteocalcin, 25(OH)D, and parathyroid hormone (PTH) were measured by ELISA assays and urinary pyridinium cross-links by HPLC. Physical activity, dietary calcium, and Tanner stage were assessed by questionnaire. In general, there were no significant differences in anthropometrical variables, physical activity, dietary calcium, serum 25(OH)D, or PTH among genotype groups. BMD or BMC of lumbar spine or whole body (adjusted for body and bone size and pubertal status) were not associated with VDR or ERalpha genotypes or the combination of these genotypes. This lack of association remained even after adjustment for dietary and environmental factors. VDR genotypes had no effect on bone turnover markers. XX and PP ERalpha genotypes were associated (P < 0.05) with reduced levels of urinary pyridinium cross-links, whereas serum osteocalcin was similar among genotypes. These findings suggest that the rate of bone resorption was influenced by ERalpha genotypes, even though these biochemical differences were not evident in bone mass indices.

Absorptiometry, Photon↗

Helicobacter pylori virulence genotypes in Portuguese children and adults with gastroduodenal pathology.

The aim of this study was to evaluate the prevalence of virulence genotypes, namely cagA, vacA and babA2, of Helicobacter pylori strains isolated from Portuguese adults and children presenting gastroduodenal pathology. One hundred thirty-six strains were studied, 82 isolated from adult patients (50 with nonulcerative gastritis and 32 with active peptic ulcer) and 58 isolated from children (54 with nonulcerative gastritis and 4 with duodenal ulcer). Genotyping of cagA, vacA and babA2 was assessed by polymerase chain reaction. Overall, Helicobacter pylori strains carrying more virulent genotypes were much more prevalent in adults than in children, particularly the type I ( vacAs1- and cagA-positive) and the triple-positive ( vacAs1-, cagA- and babA2-positive) strains ( P<0.001). A subpopulation of adults and children with nonulcerative gastritis was also studied, and differences in the prevalence of virulent genotypes were observed, either for individual genotypes ( P=0.017 for cagA, P=0.010 for vacAs1) or in combinations, i.e. the type I genotype ( P=0.005) and the triple-positive strains ( P=0.031). There was no difference between the two populations in the distribution of babA2 and m1/m2 genotypes. Considering the cohort effect in the epidemiology of Helicobacter pylori infection, these results suggest that different strains might circulate during different periods of time, or that, after infection in childhood, individual strains will undergo changes during the course of infection.

Adult↗

Glutathione S-transferase M1, T1, P1 genotypes and risk for development of colorectal cancer.

The glutathione S-transferase (GST) supergene family is an important part of cellular enzyme defense against endogenous and exogenous chemicals, many of which have carcinogenic potential. The present investigation was conducted to detect a possible association between polymorphisms at the GSTM1, GSTT1, and GSTP1 genes and the interaction with cigarette smoking and colorectal cancer incidence. We examined 181 patients with colorectal cancer and 204 controls. DNA was extracted from whole blood, and the GSTM1, GSTT1, and GSTP1 polymorphisms were determined using a real-time polymerase chain reaction and fluorescence resonance energy transfer with a Light-Cycler instrument. Associations between specific genotypes and the development of colorectal cancer were examined by use of logistic regression analysis to calculate odds ratios (OR) and 95% confidence intervals (CI). The GSTM1 polymorphism was associated with an increased risk of developing colorectal cancer (OR = 1.62, 95% CI: 1.06-2.46). Also the risk of colorectal cancer associated with the GSTT1 null genotype was 1.64 (95% CI: 1.10-2.59). Statistically no differences were found between patients with colorectal cancer and control groups for the GSTP1 Ile/Ile, Ile/Val and Val/Val genotypes. In addition, the frequencies of the GSTM1 and GSTT1 deletion genotypes differed significantly between the cases and controls for current smokers; the GSTT1 null genotype especially is associated with a greater risk of colorectal cancer (OR = 2.44, 95% CI: 1.24-4.81). The GSTM1 and GSTT1 deletions were associated with an increased risk of developing a transverse or rectal tumor (OR = 1.86, 95% CI: 1.15-3.00; OR = 1.70, 95% CI: 1.02-2.84; respectively). The glutathione S-transferase polymorphisms were not associated with risk in patients stratified by age. The risk of colorectal cancer increased as putative high-risk genotypes increased for the combined genotypes of GSTM1 null, GSTT1 null, and either GSTP1 valine heterozygosity or GSTP1 valine homozygosity (OR = 2.69, 95% CI: 1.02-7.11). In conclusion, the results obtained in this study clearly suggest that those susceptibility factors related to different GST polymorphic enzymes are predisposing for colorectal cancer.

Aged↗

Genotypic and allelic frequencies of SULT1A1 polymorphisms in women receiving adjuvant tamoxifen therapy.

Human sulfotransferase 1A1 (SULT1A1) is involved in the metabolism of a number of substances including 4-hydroxytamoxifen. It has been shown that patients who are homozygous for the variant SULT1A1 *2/*2 have lower catalytic activity. Previous data has suggested that patients with this particular genotype may be at a greater risk of developing breast cancer or not responding to tamoxifen therapy. To date, there is no data within the Hispanic population on the genotypic and allelic frequencies of the SULT1A1 gene. Two hundred and ninety-six patients were genotyped by either restriction fragment length polymorphism (RFLP) or Pyrosequencing for the SULT1A1 exon 7 polymorphism. The genotypic frequency was 0.47 (*1/*1), 0.40 (*1/*2) and 0.13 (*2/*2) in Caucasians and 0.37 (*1/*1), 0.45 (*1/*2) and 0.18 (*2/*2) in Hispanics. Although Hispanics have a higher genotypic frequency of variant genotypes this difference was not statistically significant (p=0.26). SULT1A1 genotype did not correlate with any prognostic or predictive markers associated with breast cancer. Future evaluations will assess the functional significance of this polymorphism on survival.

Antineoplastic Agents, Hormonal↗

The influence of viral genotypes and rejection episodes on the recurrence of hepatitis C after liver transplantation.

PURPOSE: The aim of this study was to report the influence of hepatitis C virus (HCV) genotype and rejection episodes on the outcome of orthotopic liver transplantation (OLT), hepatitis recurrence, and progression to graft cirrhosis after OLT. METHODS: Fifty-three patients who all had undergone OLT for end-stage liver cirrhosis were selected for this study. Hepatitis C genotype was determined. Recurrent hepatitis and rejection were diagnosed based on elevated liver function tests and a liver biopsy. RESULTS: The patients were followed up for a mean of 51.9 +/- 34.3 months. The cumulative survival rate was no different in OLT for hepatitis C and OLT for all other liver diseases. After OLT, serum HCV RNA was detected in 93%. Histological recurrence occurred in 85% of all patients. The 1-, 3-, and 5-year recurrence rates were 48%, 77%, and 85%, respectively. Of the 41 patients with recurrent hepatitis C, 4 (10%) had cirrhosis, 18 (44%) had hepatitis with fibrosis, and 91 (46%) had hepatitis without fibrosis at the end of follow-up. A total of 32% of the patients were infected by HCV genotype 1b and 68% by other HCV genotypes. The recurrence rates were significantly higher in patients infected with genotype 1b than in those with other genotypes ( p = 0.04). Twenty of 48 patients (42%) experienced acute rejection. There was a strong association between the number of rejection episodes and the incidence of HCV-related cirrhosis ( p < 0.01). CONCLUSION: Our findings showed the genotype 1b to result in a higher recurrence rate after OLT. On the other hand, rejection episodes were associated with a more rapid progression to graft cirrhosis.

Adult↗

Prevalence of hepatitis B virus genotype D in precore mutants among chronic liver disease patients from New Delhi, India.

Hepatitis B is one of the most important causes of chronic viral hepatitis world wide. Mutations in the precore region of the hepatitis B virus (HBV) genome are frequently found in hepatitis B envelope antigen-negative cases. Data from India on the HBV genotype-associated distribution of precore mutations are limited. Our objective in this study was to genotype and detect the precore mutant with a point mutation from G to A at nucleotide 1896 using ligase chain reaction (LCR) and direct sequencing. A total of 115 cases of chronic liver disease were screened. The cases were evaluated on the basis of history, clinical examination, liver function profile, and serological test for HBV infection, which includes HBsAg, anti HBcIgG, HBeAg using commercially available ELISA kits. The cases, which were HBeAg+, HBeAg-, and HBV DNA+, were subjected to LCR and confirmed by direct sequencing. Of 115 chronic liver disease cases, 50 (43.5%) cases were HBV DNA positive. All cases were subjected to LCR; 11 (22%) cases confirmed the presence of precore mutants, while the remaining 39 (78%) were classified as the wild form of the virus. HBV genotyping by direct sequencing revealed that genotype D was predominant in both wild and mutant forms of the virus. We conclude that the HBV genotype distribution was not significantly different between precore mutants and the wild form of the virus (P>0.05). North Indian patients with genotype D were more likely to have persistent HBV infection with precore mutants. HBV genotypes correlate with the clinical outcome of chronic HBV infection.

Adenine↗

Genome-wide transcriptional analysis of salinity stressed japonica and indica rice genotypes during panicle initiation stage.

Rice yield is most sensitive to salinity stress imposed during the panicle initiation (PI) stage. In this study, we have focused on physiological and transcriptional responses of four rice genotypes exposed to salinity stress during PI. The genotypes selected included a pair of indicas (IR63731 and IR29) and a pair of japonica (Agami and M103) rice subspecies with contrasting salt tolerance. Physiological characterization showed that tolerant genotypes maintained a much lower shoot Na+ concentration relative to sensitive genotypes under salinity stress. Global gene expression analysis revealed a strikingly large number of genes which are induced by salinity stress in sensitive genotypes, IR29 and M103 relative to tolerant lines. We found 19 probe sets to be commonly induced in all four genotypes. We found several salinity modulated, ion homeostasis related genes from our analysis. We also studied the expression of SKC1, a cation transporter reported by others as a major source of variation in salt tolerance in rice. The transcript abundance of SKC1 did not change in response to salinity stress at PI stage in the shoot tissue of all four genotypes. However, we found the transcript abundance of SKC1 to be significantly higher in tolerant japonica Agami relative to sensitive japonica M103 under control and stressed conditions during PI stage.

DNA Primers↗

Acute hepatitis B in Western Sweden--genotypes and transmission routes.

A retrospective study of acute hepatitis B (AHB) during 1995-1996 in Göteborg, Sweden, was carried out to investigate whether the increasing number of hepatitis B virus (HBV) carriers due to immigration in northwestern Europe has influenced the incidence or genotype heterogenicity. 24 cases of AHB were identified, the probable transmission route of which was intravenous drug use (IVDU) in 11 (46%), heterosexual in six (25%), homosexual in one, hemodialysis in two and unknown in four cases. In no case was the source an immigrant with chronic HBV infection. Genotype D was seen in 12 patients, seven being anti-HCV-positive IVD users, two probably infected heterosexually and three with an unknown source. Genotype A was found in six patients: three IVD users, a sexual partner of an IVD user and two dialysis patients. Genotype B was found in one patient infected during travel to Vietnam, and genotype C in one patient, probably infected sexually from a previously identified chronic carrier. In conclusion, genotype D is the main genotype and IVDU still the major risk factor for AHB in Goteborg, while transmission from immigrants appears to be of minor importance despite the fact that this group comprises over 90% of the young, highly infectious carriers.

Acute Disease↗

Asian domains of four major genotypes of JC virus, Af2, B1-b, CY and SC.

JC virus (JCV) strains worldwide can be classified into various genotypes based on DNA sequence variations. To define the domains of the four major JCV genotypes in Asia, we collected urine samples at six unstudied sites: three in southeastern Asia, two in the central highlands and one in central Asia. DNA was extracted from urine samples, and used to amplify a 610-bp region of the viral genome. For each geographical site, we determined 16 to 31 sequences, from which a phylogenetic tree was constructed to unambiguously classify detected JCV isolates into distinct genotypes. From JCV genotype profiles at the sites studied here and elsewhere, the following conclusions were drawn. Although Af2 is the major genotype in Africa, this genotype also occurs in western and central Asia. B1-b mainly occurs in western and central Asia, including the central highlands. CY occurs in northeastern Asia with the southern boundary between China and southeast Asian countries. Although SC predominates in southeastern Asia, it also occurs in northern and central Asia at lower frequencies. In addition, a few minor JCV genotypes (B1-a, B2 and B3) occur at many sites. We discuss here the anthropological and medical significance of the present findings.

Adult↗

Fibrinolytic activity in women on oral contraceptive pills: variation due to haemoglobin genotype.

Plasma fibrinogen levels and euglobulin lysis time (ELT) were determined in 84 women with haemoglobin genotype AA (HbAA) and in 38 with haemoglobin genotype AS (HbAS), aged 17-35 years, who were on oral contraceptive pills (OCP). The control group included 23 HbAA and 27 HbAS age-matched, apparently healthy women, who had regular menstruation and no history of OCP usage. The controls showed statistically significant elevations in fibrinogen levels in women with genotype HbAS (+13%; P < 0.05) compared with women with genotype HbAA. Among OCP users, the difference in fibrinogen levels (+5%) between HbAS and HbAA women was not statistically significant. The elevation in fibrinogen levels which was restricted to the HbAA women, was probably caused by OCP use, and may be dependent on the Hb genotype. In contrast, the observed elevations in euglobulin lysis time among OCP users (P < 0.005) were independent of Hb genotype. Thus, while OCP may constitute a risk factor for the development of thromboembolism in women, the S-gene may confer partial protection against this development in women who have the HbAS genotype.

Adolescent↗

Influence of the genotypes of hepatitis C virus on the severity of recurrent liver disease after liver transplantation.

BACKGROUND/AIMS: Several genotypes of hepatitis C virus (HCV) have been identified by phylogenetic analysis, but their clinical relevance remains elusive. Liver transplantation for HCV-related cirrhosis offers a unique opportunity for prospective studies of this issue. METHODS: Sixty anti-HCV-positive liver recipients with precise virological and histological assessments were included. HCV genotype was determined with both type-specific capsid primers and a line probe genotyping assay. RESULTS: HCV genotype 1b was the predominant type before transplantation (40 of 60 patients); after liver transplantation, acute and chronic active hepatitis developed more frequently in these patients than in patients infected by other genotypes (31 of 40 and 24 of 40 vs. 8 of 20 and 4 of 20 patients). Actuarial rates of acute hepatitis and chronic active hepatitis were 77% and 59%, respectively, 3 years after transplantation in patients infected by type 1b and 40% (P = 0.008) and 22% (P = 0.004) in those infected by other types. There was no statistical relation between the level of HCV viremia and HCV genotypes both before and after transplantation. In contrast, after transplantation, serum HCV RNA values were significantly increased in patients who developed hepatitis after transplantation. CONCLUSIONS: This study provides direct evidence that HCV 1b is associated with more aggressive recurrent liver disease than other genotypes.

Actuarial Analysis↗

Genotype, slow decrease in virus titer during interferon treatment and high degree of sequence variability of hypervariable region are indicative of poor response to interferon treatment in patients with chronic hepatitis type C.

In a study assessing factors associated with a good or a poor response to interferon treatment in patients with chronic hepatitis type C, we analyzed serum samples taken from 26 interferon-treated patients and found further evidence that infection with genotype II is associated with a poor response. Whereas all seven patients with group III genotype tested showed a good response (normalization of alanine aminotransferase level for more than 6 months), only 10 of 19 (53%) patients infected with group II genotype showed a good response. We also observed that 16 of 17 (94%) patients who exhibited a rapid virus titer decrease during the first 2 weeks of treatment later showed a good response. In contrast, only three of nine (33%) patients with an initially slow viral decrease eventually showed a good response (p<0.04). None of the 26 control patients exhibited a marked virus decrease or normalization of serum alanine aminotransferase level. Interestingly, high degrees of sequence variability were seen in three patients with group II hepatitis C virus who responded poorly to the therapy. All three showed slow decreases in virus titer during the first 2 weeks of treatment. In contrast, patients with genotype II who showed a good response to treatment were seen to have very few mutations. In three patients with genotype III who had responded well to interferon treatment, all showed very little amino acid sequence variability in the hypervariable region compared with patients with genotype II who had responded poorly to interferon treatment. These data suggest that a slow decrease in virus titer during the beginning of interferon treatment and a high degree of sequence variability, both of which are often seen in patients with group II genotype, are associated with poor response to interferon treatment.

Adult↗

HLA-DQ genotypes are associated with autoimmunity to glutamic acid decarboxylase in insulin-dependent diabetes mellitus patients.

This study has investigated the genetic basis of the heterogeneous autoimmune response to glutamic acid decarboxylase (GAD) in 179 Australian patients with IDDM. Antibodies to GAD have been correlated with HLA-DQB1 alleles and genotypes, as determined by sequence-specific oligonucleotide hybridizations after polymerase chain reaction was applied to exon 2 of the DQ beta 1 gene. HLA-DQ2 was significantly increased (p < 0.01) in IDDM patients with antibodies to GAD. Antibodies to GAD were detected in 64% of 72 DQ2.8 patients, in 55% of 29 DQ2.2 or DQ8.8 patients and in 41% of 78 patients with other HLA-DQB1 genotypes. HLA-DQ genotype association with autoimmunity to GAD was statistically significant (p = 0.02) and reflected early formation of antibodies to GAD, rather than an HLA association with persistence of antibodies to GAD, since the genotype effect was more evident (p = 0.02) in those with more recent onset (0-5 years) of IDDM. Also, the HLA-DQ genotype effect was more evident in patients with IDDM onset after the age of 14 years (p = 0.003). Multivariate analysis showed that HLA-DQB1 genotypes had a more significant impact on antibodies to GAD than either duration or age of onset of IDDM. In patients with IDDM in childhood, only a minority had low-risk HLA-DQB1 genotypes (37%) when compared with those with onset in adulthood (62%) (p = 0.005).(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Evaluation of AMPD1 C34T genotype as a predictor of mortality in heart failure and post-myocardial infarction patients.

BACKGROUND: The AMPD1 gene C34T polymorphism has previously been associated with prolonged survival in small cohorts of heart failure (HF) and coronary artery disease patients. This study aimed to corroborate the association of the AMPD1 C34T polymorphism with survival in larger myocardial infarction (MI) and HF cohorts. METHODS: Genotypes were obtained for 935 post-MI (PMI) and 433 patients with established HF, with median follow-up times of 5.4 and 3.1 years, respectively. At admission, cardiac function was assessed by nuclear ventriculography (PMI) and echocardiography (HF) and plasma cardiac neurohormones were assayed. RESULTS: Differences in mortality by AMPD1 genotype did not achieve significance, either for the overall HF (P = .07) or the overall PMI group (P = .28), but AMPD1 genotype predicted mortality in patients of both cohorts with a history of MI (HxMI). In contrast to previous studies, the mutant T allele was associated with poorer outcome. Mortality in HF HxMI patients was significantly different between genotype groups (n = 144, mortality CC 56.5%, CT/TT 77.8%, P = .027), but not in patients without HxMI. In PMI patients, the association of genotype with survival in the HxMI subgroup trended toward significance (n = 147, mortality CC 29.8%, CT/TT 45.5%, P = .093). Multivariate analysis of combined PMI and HF cohorts showed that HxMI patients with CT/TT genotype were at greater risk than all other groups (P < .001). CONCLUSION: This study suggests that AMPD1 C34T genotype is not a predictor of survival in heart disease patients, except possibly those with HxMI.

AMP Deaminase↗

Association of endothelial nitric oxide synthase genotypes with bone mineral density, bone loss, hip structure, and risk of fracture in older women: the SOF study.

Nitric oxide (NO) is an important bone-signaling molecule. We examined the associations between the Glu298Asp polymorphism of NOS3, indices of bone strength, and the incidence of fracture among 6691 women aged 65 years and older enrolled in the Study of Osteoporotic Fractures. Calcaneal BMD was measured at an initial exam and after an average of 5.9 years of follow-up. Hip BMD was measured at an initial exam and after 3.7 years of follow-up. Baseline spine BMD and hip structural parameters were measured. Incident hip fractures were confirmed by review of radiographic reports; follow-up was greater than 98% complete. Incident vertebral fractures were defined by morphometry using lateral spine radiography at baseline and an average of 3.7 years later. The frequencies of the NOS3 Glu298Asp genotypes were Glu/Glu=46.2%, Glu/Asp=42.7%, and Asp/Asp=11.1%. There were no significant associations between NOS3 genotypes and initial calcaneal BMD, hip BMD, or rate of change in hip or calcaneal BMD. None of the hip structural parameters differed substantially by genotype. NOS3 genotype was not significantly associated with either incident or prevalent radiographic vertebral fractures. Women with the heterozygous Glu/Asp genotype had a borderline statistically significantly lower rate of hip fracture than either the Glu/Glu genotype (HR=0.87, 95% CI: 0.74, 1.01) or the Asp/Asp genotype (HR=0.78, 95% CI: 0.62, 0.98). In conclusion, the Glu298Asp polymorphism does not contribute substantially or consistently to indices of bone strength in this sample of older white women, although our findings suggest allelic variation at the NOS3 locus maybe associated with hip fracture risk. Confirmation of these findings is needed in other populations and with additional markers within and flanking the NOS3 gene region.

Age Factors↗

Relation of glutathione S-transferase genotypes (GSTM1 and GSTT1) to laryngeal squamous cell carcinoma risk.

The purpose of the present study was to investigate GSTM1 and GSTT1 genotypes by using multiplex polymerase chain reaction (PCR) in patients with laryngeal squamous cell carcinoma (LSCC). The genotypes of 110 patients with LSCC and of 197 healthy subjects as the control group were determined by PCR analysis for GSTM1 and GSTT1 genes. Results showed that frequencies of GSTM1-null, GSTT1-null, and both GSTs-null genotypes were 51.8, 30, and 16.4%, respectively, in the patients with LSCC and 37.6, 15.7, and 5.6% in the control group. There was a significant difference between the genotype distributions of all GSTs in patients and in control groups (P < 0.05). The results support the hypothesis that null genotypes of GSTM1 and GSTT1 can reduce detoxification capacity of GSTs as members of the xenobiotic enzyme system. GSTM1-null, GSTT1-null, and both GSTs-null genotypes were more common in the patients with LSCC than in the control group. Patients with both GSTs-null genotypes had the highest risk for supraglottic LSCC in the early period, even if they were light-to-medium smokers. Investigation and determination of the genetic basis of LSCC may contribute to detection of risk groups and to prevent LSCC in the population.

Adult↗