RESUMEN

Persistent human papillomavirus (HPV) infection is recognized as a major risk factor for cervical cancer. Women with persistent HPV and negative cytology are at greater risk of CIN2+ than women with negative infection. The diagnosis becomes more complicated when the woman has a type 3 transformation zone at colposcopy. The aim of this study was to determine the prevalence of CIN2+ in women with persistent HPV, negative cytology and TZ3; how to stratify the risk of CIN2+; and what the best diagnostic strategy is, given TZ3. METHODS: In a multicenter retrospective cohort study, we enrolled women with negative cytology and TZ3 among the 213 women referred for colposcopy for persistent HPV. The average age of the women was 53 years; in particular, 83% were postmenopausal women. In the presence of a TZ3, the entire transformation zone cannot be explored, making colposcopy and targeted biopsy useless and inadequate, with great risks of underdiagnosis or missed diagnosis. Women with TZ3 underwent diagnostic LEEP to ensure correct diagnoses. RESULTS: The study highlighted 19% (16/84) of CIN2+ lesions, a higher frequency of non-HPV 16/18 genotypes (76.2%), and 50% of CIN2+ lesions being due to non-HPV 16/18 genotypes. Furthermore, more than half of the women (80.9%) had normal histopathological results in the LEEP sample. CONCLUSION: Women with viral persistence, negative cytology, and TZ3 have a 19% risk of CIN2+; genotyping helps stratify risk, but extensive genotyping is necessary instead of partial genotyping (16/18), referring to a population of women over 50 years old in which the prevalence of genotypes 16,18 decreases and the prevalence of other genotypes increases; diagnostic LEEP is excessive (only 16 cases of CIN2+ out of 48 cases treated), even though 83% of women had viral clearance after LEEP; p16/Ki67 double staining could be a potential risk marker, which would only highlight women at risk of CIN2+ to undergo LEEP. To individualize the diagnostic workup and treatment and minimize the risk of under diagnosis and overtreatment, future studies should explore the use of extended genotyping and new biomarkers for individual risk stratification.

RESUMEN

Objective: Screening for cervical cancer requires the participation of target women. Human papillomavirus (HPV) testing can be performed on vaginal self-samples and self-sampling can improve this participation. This study aims to validate the performance of the vaginal self-sampling device (Vitroveil®) to detect high risk human papillomavirus (hrHPV) in comparison to clinician collected samples and evaluate the degree of acceptability of the Vitroveil® device. Methods: A cross-sectional observational study was carried out in a cohort of 385 participating women (median age of 44 ± 10.47 years) attending primary care centers and cervical pathology services of Granada, Spain. Two paired samples (vaginal self-sample and clinician collected cervical sample) where collected from each participant to compare the detection of HPV with the Vitro HPV Screening assay (Vitro, Granada, Spain). A questionnaire was also provided to the participants to analyze the degree of satisfaction with the device and the preference for sampling method. Results: Overall concordance for hrHPV detection was substantial (ĸ 0.804). The prevalence of any hrHPV infection was higher in self-collected samples (30.6%) than in clinician-collected samples (24.3%). The participants found the self-sampling device easy to use and preferred self-collection as the collection method. Conclusion: The Vitroveil® self-sampling device enables safe and accruable hrHPV testing, obtaining equivalent results to those of the clinician collected samples. High acceptability of the device has been demonstrated among women in the study. Nevertheless, additional studies are necessary to verify the efficacy and reliability of the device's performance.

RESUMEN

Background: The HPV-automated visual evaluation (PAVE) Study is an extensive, multinational initiative designed to advance cervical cancer prevention in resource-constrained regions. Cervical cancer disproportionally affects regions with limited access to preventive measures. PAVE aims to assess a novel screening-triage-treatment strategy integrating self-sampled HPV testing, deep-learning-based automated visual evaluation (AVE), and targeted therapies. Methods: Phase 1 efficacy involves screening up to 100,000 women aged 25-49 across nine countries, using self-collected vaginal samples for hierarchical HPV evaluation: HPV16, else HPV18/45, else HPV31/33/35/52/58, else HPV39/51/56/59/68 else negative. HPV-positive individuals undergo further evaluation, including pelvic exams, cervical imaging, and biopsies. AVE algorithms analyze images, assigning risk scores for precancer, validated against histologic high-grade precancer. Phase 1, however, does not integrate AVE results into patient management, contrasting them with local standard care.Phase 2 effectiveness focuses on deploying AVE software and HPV genotype data in real-time clinical decision-making, evaluating feasibility, acceptability, cost-effectiveness, and health communication of the PAVE strategy in practice. Results: Currently, sites have commenced fieldwork, and conclusive results are pending. Conclusions: The study aspires to validate a screen-triage-treat protocol utilizing innovative biomarkers to deliver an accurate, feasible, and cost-effective strategy for cervical cancer prevention in resource-limited areas. Should the study validate PAVE, its broader implementation could be recommended, potentially expanding cervical cancer prevention worldwide. Funding: The consortial sites are responsible for their own study costs. Research equipment and supplies, and the NCI-affiliated staff are funded by the National Cancer Institute Intramural Research Program including supplemental funding from the Cancer Cures Moonshot Initiative. No commercial support was obtained. Brian Befano was supported by NCI/ NIH under Grant T32CA09168.

Asunto(s)

Infecciones por Papillomavirus , Neoplasias del Cuello Uterino , Humanos , Femenino , Neoplasias del Cuello Uterino/diagnóstico , Neoplasias del Cuello Uterino/prevención & control , Detección Precoz del Cáncer , Infecciones por Papillomavirus/diagnóstico , Vagina , Algoritmos

RESUMEN

BACKGROUND: The US Food and Drug Administration supports innovations to facilitate new indications for high-risk human papillomavirus testing. This report describes the retrospective testing of stored specimens and analysis of existing data to efficiently and cost-effectively support a new indication for the Onclarity human papillomavirus assay (Becton, Dickinson and Company, BD Life Sciences - Integrated Diagnostic Solutions, Sparks, MD). The performance of this index test was compared with that of a predicate test, the cobas human papillomavirus assay (Roche Diagnostics, Indianapolis, IN). Both human papillomavirus assays are based on real-time polymerase chain reaction platforms that detect the presence of 14 high-risk human papillomavirus genotypes. The predicate assay reports human papillomavirus types 16 and 18 as individual results and the other 12 human papillomavirus genotypes as 1 pooled result. The index assay reports 9 independent results (human papillomavirus types 16, 18, 31, 33/58, 35/39/68, 45, 51, 52, and 56/59/66). Both the index and predicate assays are approved by the Food and Drug Administration for cervical cancer screening, but at the time that this study was initiated, the index human papillomavirus assay was not approved for use with cervical specimens collected in PreservCyt (Hologic, Inc, San Diego, CA) liquid-based cytology media. OBJECTIVE: The performance of the index human papillomavirus assay was compared with that of the predicate human papillomavirus assay for the detection of cervical intraepithelial neoplasia grades 2 or greater and 3 or greater (≥CIN2 or ≥CIN3) using PreservCyt liquid-based cytology specimens collected from women aged 21 to 65 years. In addition, the ability of the index test's extended genotyping to stratify ≥CIN2 and ≥CIN3 risks, using these specimens, was evaluated. STUDY DESIGN: The New Mexico HPV Pap Registry was used to select an age- and cytology-stratified random sample of 19,879 women undergoing opportunistic cervical screening and follow-up in routine clinical practice across New Mexico. A subset (n = 4820) of PreservCyt specimens was selected from 19,879 women for paired testing by the index and predicate human papillomavirus assays within age and cytology strata and included women with or without cervical biopsy follow-up. Point estimate differences and ratios were calculated for cervical disease detection and positivity rates, respectively, with 95% confidence intervals to determine statistical significance. The cumulative risk of ≥CIN2 or ≥CIN3, with up to 5-year follow-up, was estimated for the index assay using Kaplan-Meier methods. RESULTS: The 5-year cumulative ≥CIN3 detection rates were 5.6% for the index assay and 4.6% for the predicate assay (difference, 1.0%; 95% confidence interval, 0.5%-1.5%). The ≥CIN3 positivity rates within <1 year were 95.3% for the index assay and 94.5% for the predicate assay (ratio, 1.01; 95% confidence interval, 0.98-1.06). The ≥CIN3 cumulative positivity rates for the index and predicate assays were also similar at 5 years. Among cases of ≥CIN3, the positive agreement rates between the index and predicate assays for human papillomavirus types 16 and 18 were 100.0% (95% confidence interval, 95.0%-100.0%) and 90.9% (95% confidence interval, 62.3%-98.4%), respectively. Human papillomavirus type 16 carried the highest ≥CIN2 or ≥CIN3 risk, followed by human papillomavirus types 18/31/33/58/52/45 and human papillomavirus types 35/56/59/51/56/59/66. CONCLUSION: The index and predicate human papillomavirus assays demonstrated equivalent performance, and extended human papillomavirus genotyping, using the index assay, provided effective ≥CIN2 and ≥CIN3 risk stratification, supporting a new indication for use of the index assay with PreservCyt.

Asunto(s)

Infecciones por Papillomavirus , Displasia del Cuello del Útero , Neoplasias del Cuello Uterino , Femenino , Estados Unidos/epidemiología , Humanos , Neoplasias del Cuello Uterino/patología , Detección Precoz del Cáncer , Estudios Retrospectivos , Displasia del Cuello del Útero/patología , Papillomaviridae/genética , Papillomavirus Humano 16/genética , New Mexico , Genotipo

RESUMEN

BACKGROUND: Optimizing the balance between colposcopy referrals and the detection of high-grade cervical intraepithelial neoplasia (CIN) during cervical cancer screening requires robust triage strategies. We evaluated the performance of extended HPV genotyping (xGT), in combination with cytology triage, and compared it to previously published performance data for high-grade CIN detection by HPV16/18 primary screening in combination with p16/Ki-67 dual staining (DS). METHODS AND MATERIALS: The baseline phase of the Onclarity trial enrolled 33,858 individuals, yielding 2978 HPV-positive participants. Risk values for ≥CIN3 were determined for Onclarity result groupings corresponding to HPV16, not HPV16 but HPV18 or 31, not HPV16/18/31 but HPV33/58 or 52, not HPV16/18/31/33/58/52 but HPV35/39/68 or 45 or 51 or 56/59/66 across all cytology categories. Published data from the IMPACT trial for HPV16/18 plus DS was utilized as a comparator during ROC analyses. RESULTS: There were 163 ≥ CIN3 cases detected. The ≥CIN3 risk stratum hierarchy (% risk of ≥CIN3) that resulted from this analysis included: >LSIL (39.4%); HPV16, ≤LSIL (13.3%); HPV18/31, ≤LSIL (5.9%); HPV33/58/52/45, ASC-US/LSIL (2.4%); HPV33/58/52, NILM (2.1%); HPV35/39/68/51/56/59/66, ASC-US/LSIL (0.9%); and HPV45/35/39/68/51/56/59/66, NILM (0.6%). For ≥CIN3 ROC analysis, the optimal cutoff for sensitivity versus specificity was approximated between not HPV16 but HPV18 or 31, any cytology (≥CIN3 sensitivity = 85.9% and colposcopy-to- ≥ CIN3 = 7.4) and not HPV16/18/31 but HPV33/58/52, NILM (≥CIN3 sensitivity = 94.5% and colposcopy-to- ≥CIN3 = 10.8). HPV16/18 with DS triage showed a sensitivity of 94.3%, with a colposcopy-to- ≥ CIN3 ratio of 11.4. CONCLUSIONS: xGT performed similarly compared to HPV primary screening plus DS for detection of high-grade CIN. xGT provides results that stratify risk in a flexible and reliable manner for colposcopy risk thresholds set by different guidelines or organizations.

Asunto(s)

Células Escamosas Atípicas del Cuello del Útero , Infecciones por Papillomavirus , Displasia del Cuello del Útero , Neoplasias del Cuello Uterino , Femenino , Embarazo , Humanos , Neoplasias del Cuello Uterino/diagnóstico , Genotipo , Infecciones por Papillomavirus/diagnóstico , Detección Precoz del Cáncer , Colposcopía , Papillomavirus Humano 16/genética , Medición de Riesgo , Papillomaviridae/genética

RESUMEN

Human papillomavirus (HPV) partial genotyping (PGT) identifies HPV16 and HPV18 individually, alongside 12 other high-risk HPV genotypes (hrHPV) collectively. HPV extended genotyping (XGT) identifies four additional hrHPV individually (HPV31, 45, 51, and 52), and reports the remaining eight in three groups (HPV33|58; 56|59|66; 35|39|68). Quality-adjusted life years (QALY), health care resource use, and costs of XGT were compared to PGT for cervical cancer screening in Singapore using DICE simulation. Women with one of the three hrHPV identified by XGT (HPV35|39|68; 56|59|66; 51), and atypical squamous cells of undetermined significance (ASCUS) on cytology, are recalled for a repeat screening in one year, instead of undergoing an immediate colposcopy with PGT. At the repeat screening, the colposcopy is performed only for persistent same-genotype infections in XGT, while with PGT, all the women with persistent HPV have a colposcopy. Screening 500,122 women, aged 30-69, with XGT, provided an incremental cost-effectiveness ratio (ICER) versus PGT of SGD 16,370/QALY, with 7130 (19.4%) fewer colposcopies, 6027 (7.0%) fewer cytology tests, 9787 (1.6%) fewer clinic consultations, yet 2446 (0.5%) more HPV tests. The XGT ICER remains well below SGD 100,000 in sensitivity analyses, (-SGD 17,736/QALY to SGD 50,474/QALY). XGT is cost-effective compared to PGT, utilizes fewer resources, and provides a risk-based approach as the primary cervical cancer screening method.

RESUMEN

OBJECTIVES: The Onclarity cervical cancer screening trial was designed to establish the clinical validity of the Onclarity HPV assay for extended genotyping (xGT) during detection of high-grade cervical neoplasia grades 2 or 3 (≥CIN2 or ≥CIN3). Here, three-year follow up data is presented to evaluate the overall efficacy of these screening strategies, compared to the baseline data. METHODS: At baseline 29,513 women, ≥25 years, had evaluable cytology and valid high-risk HPV results. Women with atypical squamous cells-undetermined significance or worse cytology or a positive HPV test were referred for colposcopy/biopsy. Participants that did not reach the study end point (treatment for ≥CIN2) continued into the longitudinal phase that included the same protocol as baseline. RESULTS: The three-year cumulative incident risk (CIR) for ≥CIN3 in HPV-negative women was 0.15% [95%CI: 0.06, 0.26] and for HPV- and cytology-negative women was 0.12% [95% CI: 0.03,0.23]. HPV16 carried the highest baseline and three-year ≥CIN3 CIR, followed by HPV31 and HPV18. At least one year of genotype-specific persistence increased ≥CIN3 risk for xGT results compared to genotype non-persistence, HPV clearance, or new infection over the same time period. Risk-based screening with immediate colposcopy for HPV16/18/31 and further xGT triage resulted in better ≥CIN3 sensitivity (79.2% versus 72.3%; relative difference of 6.9 [95%CI: 3.3, 10.4]) and a lower colposcopy/≥CIN3 ratio (9.2 versus 11.2; relative difference of -1.9 [95%CI: -2.6, -1.3]) when compared to primary HPV16/18-based screening. CONCLUSIONS: An HPV-negative result offers the same assurance of no disease over three years of follow up as that offered by a negative co-testing result. xGT facilitates risk-based screening and persistence tracking and can help optimize disease detection during screening without excessive colposcopic procedures.

Asunto(s)

Infecciones por Papillomavirus , Displasia del Cuello del Útero , Neoplasias del Cuello Uterino , Femenino , Humanos , Neoplasias del Cuello Uterino/patología , Genotipo , Papillomavirus Humano 16/genética , Detección Precoz del Cáncer/métodos , Papillomavirus Humano 18/genética , Papillomaviridae/genética , Frotis Vaginal/métodos

RESUMEN

Background: In Singapore, the current cervical cancer screening (CCS) coverage rate of 48% falls below the national target of 70%. Health care providers (HCPs) play a critical role in promoting CCS uptake. However, there is limited understanding of the perspectives of HCPs regarding CCS. Hence, we aimed to understand the challenges encountered by HCPs delivering CCS in different care settings in the Singapore health system. We also aimed to explore perspectives on newer features of CCS such as self-sampling and HPV genotyping. Methods: Physicians, nurses, program administrators and laboratory technicians involved with CCS were invited for a one-on-one semi-structured interview conducted over Zoom between May to August 2021. The interviews were transcribed and analyzed using thematic analysis. Results: Eighteen HCPs from 12 institutions were interviewed. Most participants were women (61.1%) and worked in public health institutions (72.2%). For factors influencing CCS, nine key themes were identified and organized into four categories: (1) patient factors, (2) HCP factors, (3) health system factors and (4) health promotion factors. Key themes commonly highlighted by study participants were related to patients' preferences and acceptance for screening, the processes of delivering CCS, the national priority for cervical cancer and the effectiveness of existing health promotion efforts. Five key themes were identified for CCS innovations. Self-sampling was viewed favorably to increase CCS uptake, while primary HPV screening with HPV partial genotyping had higher sensitivities to detect pre-cancers and cancers compared to cytology. Extended HPV genotyping beyond HPV16/18 could play an important role in CCS with increasing HPV vaccination coverage, as well as in the management of persistent HPV infection. Conclusion: In Singapore, HCPs face multiple challenges for CCS in practice. Insights from this study are directly relevant to, and useful for developing policies around national CCS programs and treatment guidelines.

Asunto(s)

Infecciones por Papillomavirus , Neoplasias del Cuello Uterino , Detección Precoz del Cáncer , Femenino , Personal de Salud , Papillomavirus Humano 16 , Papillomavirus Humano 18 , Humanos , Masculino , Infecciones por Papillomavirus/diagnóstico , Infecciones por Papillomavirus/prevención & control , Singapur , Neoplasias del Cuello Uterino/diagnóstico , Neoplasias del Cuello Uterino/prevención & control

RESUMEN

OBJECTIVE: To evaluate the Turkey's nationwide HPV DNA screening program on the basis of first 4 million screened women. METHODS: Women over age 30 were invited for screening via HPV DNA and conventional cytology. Single visit screen strategy was used to collect for both screening and triage (extended genotyping and conventional pap-smear). RESULTS: A total of 4,099,230 patients had attended to HPV DNA cancer screening. 4.39% were found to be HPV DNA positive. The most common HPV type was 16, followed by 51, 31, 52, 56 and 18 at all age intervals and geographic regions. Cytology results were reported as "normal" in (69.2%), "inadequate sampling" in (16.6%) and as "abnormal (≥ASC-US)" in the remaining. Current Turkish screening with HPV DNA (referral to colposcopy with HPV 16 or 18 or any smear abnormality ≥ASC-US) gives overall PPV of 24.3% for ≥CIN2. Only Pap-Smear triage revealed PPV of 26.4% for ≥ASC-US thresholds. Comparison of different triage methods for ≥CIN2+ according to different HPV genotype revealed a PPV of 32,6% for HPV 16; 15,3% for HPV 18. This figure was 34.4%, 19.3%, 15.3% and 14.0% for HPV 33, 31, 45 and 35; respectively. CONCLUSION: This study involves the largest series in the world summarizing a real-world experience with primary HPV DNA screening and triage with a single visit. The results show the feasibility and applicability of such screening method in developing countries with acceptable colposcopy referral rates. Among triage tests, only pap-smear seems to be effective without a need for extended genotyping.

Asunto(s)

Alphapapillomavirus/aislamiento & purificación , Infecciones por Papillomavirus/epidemiología , Infecciones por Papillomavirus/virología , Displasia del Cuello del Útero/epidemiología , Displasia del Cuello del Útero/virología , Neoplasias del Cuello Uterino/epidemiología , Neoplasias del Cuello Uterino/virología , Adulto , Alphapapillomavirus/genética , ADN Viral/análisis , ADN Viral/genética , Detección Precoz del Cáncer , Femenino , Genotipo , Humanos , Persona de Mediana Edad , Prueba de Papanicolaou , Infecciones por Papillomavirus/patología , Triaje , Turquía/epidemiología , Neoplasias del Cuello Uterino/patología , Displasia del Cuello del Útero/patología

RESUMEN

The objective of our study was to assess the performance of different triage strategies for high-risk human papillomavirus (hrHPV)-positive results utilizing either extended genotyping or a p16/Ki-67 dual-stained cytology (DS) approach, with or without partial genotyping. A subset of women with hrHPV infections participating in the Addressing the Need for Advanced HPV Diagnostics (ATHENA) study were analyzed to determine the number of cervical intraepithelial neoplasia grade 3 or worse (≥CIN3) cases detected, and the absolute risk for ≥CIN3 of each genotype. A clinical utility table was constructed to compare the impact of different triage strategies. In all, 2,339 women with single-genotype hrHPV infections were identified. Among these were 171 ≥CIN3 cases. The U.S. Food and Drug Administration (FDA)-approved algorithm (HPV16/18 positive, or 12-other hrHPV positive and Pap positive, i.e., ≥ atypical squamous cells of undetermined significance) for primary HPV screening detected 132/171 (77.2%) ≥CIN3 cases and required 964 colposcopies (colposcopies per ≥CIN3 ratio: 7.3). An approach that uses DS instead of cytology in the FDA-approved algorithm detected 147/171 (86.0%) ≥CIN3 cases, requiring 1,012 colposcopies (ratio: 6.9). Utilizing DS for triage of all hrHPV-positive women identified 126/171 (73.7%) ≥CIN3 cases, requiring 640 colposcopies (ratio: 5.1). A strategy that detected HPV16/18/31/33/35+ captured 130/171 (76.0%) ≥CIN3 cases, requiring 1,025 colposcopies (ratio: 7.9). Inclusion of additional genotypes resulted in greater disease detection at the expense of higher colposcopy ratios. Substituting cytology with a DS triage approach improved disease detection and the colposcopy detection rate. Further reduction of colposcopy rates can be achieved by using DS without partial genotyping. Extended genotyping strategies can identify a comparable number of cases but requires an increased number of colposcopies.

Asunto(s)

Inhibidor p16 de la Quinasa Dependiente de Ciclina/metabolismo , Antígeno Ki-67/metabolismo , Tamizaje Masivo/normas , Papillomaviridae/genética , Infecciones por Papillomavirus/diagnóstico , Triaje/normas , Neoplasias del Cuello Uterino/diagnóstico , Adulto , Anciano , Anciano de 80 o más Años , Citodiagnóstico , ADN Viral/análisis , Femenino , Estudios de Seguimiento , Genotipo , Humanos , Persona de Mediana Edad , Papillomaviridae/clasificación , Papillomaviridae/aislamiento & purificación , Infecciones por Papillomavirus/complicaciones , Infecciones por Papillomavirus/virología , Pronóstico , Estudios Retrospectivos , Neoplasias del Cuello Uterino/epidemiología , Neoplasias del Cuello Uterino/virología , Adulto Joven , Displasia del Cuello del Útero/diagnóstico , Displasia del Cuello del Útero/epidemiología , Displasia del Cuello del Útero/virología

RESUMEN

OBJECTIVES: There is growing interest in using human papillomavirus (HPV) genotyping as a risk-based triage approach for women with atypical squamous cells-undetermined significance (ASC-US) and low-grade squamous intraepithelial lesions (LSIL) cytology. METHODS: This analysis includes 2807 subjects with ASC-US or LSIL cytology, ≥21 years, from the baseline phase of the Onclarity HPV trial. All women were referred to colposcopy/biopsy. Hierarchical-ranked prevalence and risk values, associated with high-grade cervical disease, were calculated based on extended genotyping. RESULTS: HPV 16 carried the highest risk for cervical intraepithelial neoplasia grade 2 or worse (≥CIN2) in both the ASC-US and LSIL populations. Risk of ≥CIN3 and ≥CIN2 associated with the other 13 genotypes varied somewhat for women with ASC-US and LSIL, however, HPV 31, 18, 33/58, 51 and 52 appear to comprise an intermediate risk band. Risk associated with HPV 35/39/68, 45, and 56/59/66, in either cytology population, was relatively low and beneath the benchmark threshold risk for immediate colposcopy. Restricting the analysis to women 21-24 years, ≥25 years, or ≥30 years produced similar results. CONCLUSIONS: HPV genotyping identified multiple risk bands for ≥CIN3 and ≥CIN2 in the ≥21 year-old ASC-US and LSIL populations. These results support a 1-year follow-up period to preclude immediate colposcopy for ASC-US or LSIL women positive for the lowest-risk HPV genotypes.

Asunto(s)

Células Escamosas Atípicas del Cuello del Útero/virología , Tamizaje Masivo/estadística & datos numéricos , Papillomaviridae/genética , Infecciones por Papillomavirus/epidemiología , Lesiones Intraepiteliales Escamosas de Cuello Uterino/virología , Adulto , Anciano , Anciano de 80 o más Años , Colposcopía/estadística & datos numéricos , Estudios Transversales , Femenino , Genotipo , Humanos , Tamizaje Masivo/instrumentación , Persona de Mediana Edad , Papillomaviridae/aislamiento & purificación , Infecciones por Papillomavirus/genética , Factores de Riesgo , Estados Unidos/epidemiología , Adulto Joven

RESUMEN

OBJECTIVES: Increasing evidence suggests that extended human papillomavirus (HPV) genotyping (beyond 16/18) is effective for risk stratification in women with normal cytology. This report provides extended genotyping results, using the BD Onclarity HPV Assay, for individual genotypes HPV16, 18, 31, 45, 51, and 52 ̶ and three pooled genotype results for HPV33/58, 35/39/68, and 56/59/66. METHODS: 27,037 women with normal cytology, ≥25 years, were enrolled into the Onclarity HPV trial during routine screening. Women positive for any HPV genotype were referred to colposcopy/biopsy. Hierarchical-ranked prevalence and risk values, associated with cervical intraepithelial neoplasia, grade 2 or worse (≥CIN2) or ≥CIN3, were calculated based on extended genotyping results. RESULTS: HPV 16 and 31 carried the highest risk for ≥CIN2 (11.6% and 12.1%, respectively) and ≥CIN3 (8.1% and 7.5%, respectively); these genotypes were the most prevalent in both ≥CIN2 (29.6% and 19.3%, respectively) and ≥CIN3 (43.7% and 22.5%, respectively). Of the other 12 genotypes, HPV 18, 33/58, and 52 comprised an intermediate risk band (≥CIN2 risk range: 4.9-6.8%; ≥CIN3 risk range: 3.9-5.0%). Genotypes 45, 51, 35/39/68, and 56/59/66 constituted the lowest risk band for both disease grades (≥CIN2 value risk range: 1.7-3.0%; ≥CIN3 value risk range: 1.2-3.6%). CONCLUSIONS: Extended genotyping stratifies risk for ≥CIN2/3 in the ≥25 year-old, normal cytology population. While baseline HPV 16/31 values exceeded the risk threshold for colposcopy referral, the management of women with normal cytology who were positive for the intermediate- or lower-risk genotypes may evolve based on refined risk estimates as well as clinical factors.

Asunto(s)

Papillomaviridae/genética , Infecciones por Papillomavirus/patología , Infecciones por Papillomavirus/virología , Displasia del Cuello del Útero/virología , Neoplasias del Cuello Uterino/patología , Neoplasias del Cuello Uterino/virología , Adulto , Cuello del Útero/citología , Cuello del Útero/patología , Cuello del Útero/virología , Femenino , Genotipo , Papillomavirus Humano 16/genética , Papillomavirus Humano 31/genética , Humanos , Estudios Longitudinales , Clasificación del Tumor , Infecciones por Papillomavirus/epidemiología , Prevalencia , Riesgo , Neoplasias del Cuello Uterino/epidemiología , Displasia del Cuello del Útero/epidemiología , Displasia del Cuello del Útero/patología

RESUMEN

AIM OF THE STUDY: Current knowledge of the molecular basis of most blood groups enables genetic testing for blood groups to overcome the limitations of agglutination. A retrospective review was carried out on genotyping assays performed between 2011 and 2013. METHODS AND PATIENTS: The Molecular Hematology Laboratory of the EFS Alpes-Méditerranée implements commercially available tools (BioArray, Gen-Probe) and other techniques (TaqMan, tetra-primer ARMS-PCR, sequencing). It provides a high-level of expertise in molecular biology, complying with regulatory requirements and standards. RESULTS: A total of 2382 genotyping assays was performed including 764 extended typings and 115 large extended typings essentially in cases involving multiple transfusion and suspected rare blood type. Phenotype discrepancies linked to the RH system accounted for 1501 genotypings. Discrepancies linked to the D and E were mainly related to an allele coding for weak antigen (weak D type 1, 2, 3 and EIV) while those linked to C, c and e antigens were related to an allele coding for a partial antigen (RN, ces(340), ceMo). A high prevalence of (C)ces haplotype in trans of a DAR allele was observed in Afro-Caribbean (54/62). CONCLUSION: In transfusion medicine, red-cell genotyping can overcome the limitations of hemagglutination. It must be used only in situations where it provides a benefit either for the patient or resource management. For implementation of appropriate transfusional practices, this technique requires a sound knowledge of the genetic characteristics of blood groups and clinically relevant variants. It also requires competency with molecular biology tools and continuously updated scientific data.

Asunto(s)

Antígenos de Grupos Sanguíneos/genética , Tipificación y Pruebas Cruzadas Sanguíneas , Transfusión de Eritrocitos , Técnicas de Genotipaje , Alelos , ADN/genética , Francia , Frecuencia de los Genes , Genotipo , Técnicas de Genotipaje/estadística & datos numéricos , Humanos , Fenotipo , Estudios Retrospectivos , Sistema del Grupo Sanguíneo Rh-Hr/genética , Reacción a la Transfusión/prevención & control