Real-world data on cervical cancer risk stratification by cytology and HPV genotype to inform the management of HPV-positive women in routine cervical screening.
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ABSTRACT: Background
HPV16/18 detection may improve cervical cancer risk stratification and better guide which HPV-positive women warrant immediate colposcopy/biopsy. We estimated risks of cervical precancer and cancer by HPV genotype and cytology during the implementation phase of primary HPV testing in Norway.Methods
A total of 3111 women, aged 34-69 years, testing HPV-positive at baseline and undergoing cytology testing from February 2015 to April 2018 had data available for analysis. Risk estimates with 95% confidence intervals (95%CIs) of cervical intraepithelial neoplasia grade 3 or more severe (CIN3+) were estimated for cytology results and HPV genotypes (HPV16, HPV18, and other high-risk HPV).Results
CIN3+ risks were higher for HPV16/18 than other high-risk HPV genotypes. Among women with any cytologic abnormality [atypical squamous cells of undetermined significance or worse], immediate risks were 57.8% (95%CI = 53.0-62.6%) for HPV16, 40.2% (95%CI = 32.3-49.2%) for HPV18, and 31.4% (95%CI = 28.7-34.3%) for other high-risk HPV. Among those with normal cytology, CIN3+ risks were 19.9% (95%CI = 15.0-26.1%) for HPV16 positives, 10.8% (95%CI = 5.6-20.5%) for HPV18 positives, and 5.5% (95%CI = 4.2-7.1%) for other high-risk HPV.Conclusions
The benefits and harms of managing women based on HPV positivity and cytology results can be better balanced by inclusion of HPV genotyping in screening and choosing more conservative management for other high-risk HPV compared to HPV16/18.
SUBMITTER: Hashim D
PROVIDER: S-EPMC7250848 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Background. There are limited data on high-risk human papillomavirus (hr-HPV) genotypes among HIV-positive women in Africa, and little is known about their relationship with cervical cytology in these populations. Methods. We conducted a cross-sectional study among 194 HIV-positive women (143 from Tanzania, and 51 from South Africa) to evaluate HPV genotypes among HIV-positive women with normal and abnormal cytology. Cervical samples were genotyped for HPV types, and slides were evaluated for atypical squamous cell changes according to the Bethesda classification system. Results. Prevalence of high grade squamous intraepithelial dysplasia (HSIL) was 9%. Overall, more than half (56%) of women were infected with an hr-HPV type; 94% of women with HSIL (n = 16), 90% of women with LSIL (n = 35), and 42% of women within normal limits (WNL) (n = 58) tested positive for hr-HPV. Overall, the most prevalent hr-HPV subtypes were HPV16 (26%) and HPV52 (30%). Regional differences in the prevalence of HPV18 and HPV35 were found. Conclusion. Regional differences in HPV genotypes among African women warrant the need to consider different monitoring programmes for cervical preneoplasia. HPV-based screening tests for cervical preneoplasia would be highly inefficient unless coupled with cytology screening of the HPV-positive sample, especially in HIV-positive women.
| S-EPMC3394385 | biostudies-literature
Project description:BackgroundSelf-sampling for human papillomavirus (HPV) testing is a feasible option to improve the cervical screening coverage. However, an ideal triage method for HPV-positive self-samples does not yet exist. The aim of this study was to explore the utility of HPV genotyping and p16INK4a immunostaining (p16) in triaging HPV-positive self-samples, focusing on HPV-positive, cytology-negative (HPCN) women.MethodsA total of 73,699 women were screened in a cervical screening project in China via SeqHPV assay on self-samples. HPV-positive women were called-back and collected cervical sample for p16 immunostaining and liquid-based cytology, those who met any result of HPV16/18+ or visual inspection with acetic acid (VIA) + or p16+ were referred for colposcopy, and HPCN women with adequate data on p16 and pathology were analyzed. A triage strategy was considered acceptable if the negative predictive value (NPV) for cervical intraepithelial neoplasia 3 or worse (CIN3+) was 98% or more, combined with an improvement of sensitivity and specificity for CIN2+/CIN3+ in reference to the comparator, being HPV16/18 + .ResultsA total of 2731 HPCN women aged 30-64 years were enrolled, 136 (5.0%) CIN2+ and 53 (1.9%) CIN3+ were detected. Five triage strategies met the criteria: p16+; HPV16/33+; 'HPV16+ or HPV33/58/31/35+&p16+'; 'HPV16/33+ or HPV58/31/35+&p16+'; HPV16/18/31/33/45/52/58 + & p16+. These strategies required less or similar colposcopy referrals, and less colposcopies to detected one case of CIN2+/CIN3+, achieving favorable false positive (negative) rates to the comparator. Among them, p16 staining detected 83.1% (79.2%) of underlying CIN2 + (CIN3+) in HPCN women. Moreover, three triage strategies were favorable in sensitivity and/or specificity to the 'HPV16/33+' strategy: p16+; 'HPV16+ or HPV33/58/31/35 + &p16+'; HPV16/18/31/33/45/52/58 + &p16 + .ConclusionsGenotyping for HPV16/33 could be utilized to optimize the management of HPCN women. Moreover, p16 immunostaining, either alone or combined with extended genotypes, is more effective than HPV genotypes alone in the triage of HPCN women.
| S-EPMC8086315 | biostudies-literature
Project description:The assessment of human papillomavirus (HPV) genotype dynamics could support the adoption of more tailored preventive actions against cervical cancer. The aim of the study was to describe the prevalence of HPV infection, HPV genotype distribution, and the epidemiological characteristics of women with ASC-US cytology since the introduction of HPV-DNA testing in Sardinia (Italy), (March 2016-December 2020). Specimens were tested by RT-PCR for 14 high-risk HPV genotypes. A total of 1186 patients were enrolled, with a median (IQR) age of 41 (38-48) years. Of these women, 48.1% were positive for at least one HPV genotype; 311 (26.2%) women were vaccinated with a median (IQR) age of 38 (30/47) years. The percentage of prevalence of HPV-16, -31, -66, -56, and -51 was 36.3%, 18.7%, 11.9%, 11.4% and 10.7%, respectively. The highest prevalence of infection was found in women aged <41 years, and single women. Moreover, women aged >41 years (OR: 0.51, 95% CI: 0.31-0.86; p-value: 0.01), having parity (OR: 0.57, 95% CI: 0.34-0.96, p-value: 0.04), and higher educational level (OR: 0.39, 95% CI: 0.18-0.87; p-value: 0.02) were associated with a lower CIN2+ risk. We did not find a significant difference in terms of prevalence of HPV-16 infection between vaccinated and non-vaccinated (18.3% vs. 17.1%; p-value < 0.001). Our results support the adoption of nonavalent HPV-vaccine to prevent the most prevalent infections caused by HPV-16 and -31 genotypes and underscore the need of surveillance to implement tailored vaccination programs and preventive strategies.
| S-EPMC8775344 | biostudies-literature
Project description:We compared American Thyroid Association (ATA) guidelines, Korean (K)-Thyroid Imaging, Reporting and Data Systems (TIRADS), EU-TIRADS, and American College of Radiology (ACR) TIRADS in diagnosing malignancy for thyroid nodules with nondiagnostic/unsatisfactory cytology. Among 1143 nondiagnostic/unsatisfactory aspirations from April 2011 to March 2016, malignancy was detected in 39 of 89 excised nodules. The minimum malignancy rate was 7.82% in EU-TIRADS 5 and 1.87-3.00% in EU-TIRADS 3-4. In the other systems, the minimum malignancy rate was 14.29-16.19% in category 5 and ≤3% in the remaining categories. Although the EU-TIRADS category ≥ 5 exhibited the highest positive likelihood ratio (LR) of only 2.214, category ≥ 5 in the other systems yielded the highest positive LR of >5. Receiver operating characteristic (ROC) curves of all systems to predict malignancy were located statistically above the diagonal nondiscrimination line (P for ROC curve: EU-TIRADS, 0.0022; all others, 0.0001). The areas under the ROC curve (AUCs) were not significantly different among the four systems. The ATA guidelines, K-TIRADS, and ACR TIRADS may be useful to guide management for nondiagnostic/unsatisfactory nodules. The EU-TIRADS, although also useful, exhibited inferior performance in predicting malignancy for nondiagnostic/unsatisfactory nodules in Korea, an iodine-sufficient area.
| S-EPMC8073392 | biostudies-literature
Project description:BackgroundCervical cancer is the second most prevalent cancer among women of child-bearing age in Ethiopia. The aim of this study was to determine human papilloma virus (HPV) genotype distribution among HIV-negative women with normal and abnormal cervical cytology results.MethodsWe investigated a consecutive of 233 HIV-negative women between December 2008 and March 2009 presenting in a Tertiary Gynecology Referral Clinic in Ethiopia. Screening was done by Pap cytology and HPV detection and genotyping method was nested PCR (direct amplification with MY09/MY11 primers, followed by nested amplification with GP5/GP6 primers) and sequencing of the nested products. Sequencing of the non-purified nested PCR products was performed following re-amplification with Big dye terminator, using the GP6 primer.ResultsOf the 233 study participants, 92 (39.5%) had abnormal cytology. All women with abnormal cervical cytology had positive HPV DNA compared to only 48.9% of those presenting with normal cytology. Of these women, the frequency of high-risk (HR)-HPV was 83.2% and its prevalence in women with abnormal cervical cytology was significantly higher than those with normal cytology (92.4% vs. 71%, p < 0.0001). The most frequent genotypes identified were HPV16 (44.1%), followed by HPV35 and HPV45 (each 6.2%), HPV31 (4.4%), HPV56 (3.7%), HPV18 and HPV59 (each 3.1%), HPV58 (2.5%) and HPV39 (1.9%). While the most common HR-HPV infections among women with normal cytology were HPV16 (20.3%), followed by HPV35 (8.7%), HPV56 and HPV58 (each 5.8%), HPV18, HPV31 and HPV39 (each 4.4%), HPV45 (2.9%) and HPV59 and HPV68 (each 1.5%), the most common HR-HPV infections in women with abnormal cytology included HPV16 (62%), followed by HPV45 (8.7%), HPV 31, HPV35 and HPV59 (each 4.4%), and HPV18, HPV52 and HPV56 (each 2.2%). We also noted low prevalence of multiple HPV infections in women with normal or abnormal cytology. Multivariable logistic analysis showed that residing in rural area (OR 3.24, 95% CI: 1.13-9.30), being multipara (OR 7.35, 95% CI: 1.78-30.38) and having abnormal cervical cytology results (OR 6.75, 95% CI: 1.78-25.57) were all independently associated with HPV16 genotype.ConclusionsOur study revealed a significant risk of infection with HR-HPV, in particular with HPV16 genotype, in women attending a referral center in Ethiopian women presenting with or without abnormal cervical cytology. Moreover, Pap smear cytology missed a significant proportion of women compared to those who were identified by PCR for HR-HPV infections. In addition, the PCR method we used was not suitable for sensitive detection of co-existent multiple infections. Data from the present study indicate that currently available HPV vaccines could prevent nearly 67% of all cervical cancer cases in women in Ethiopia.
| S-EPMC6092870 | biostudies-literature
Project description:OBJECTIVES:To assess the clinical and cost-effectiveness of human papillomavirus (HPV) primary screening triage with p16/Ki-67 dual stain cytology compared to cytology. METHODS:We conducted an Excel®-based budget impact model to estimate the preinvasive and invasive cervical cancer cases identified, mortality rate, direct medical costs, quality-adjusted life years (QALYs) and the incremental cost-effectiveness analysis of two strategies from the healthcare payer perspective. The study population is a cohort of women 30-65 years of age presenting for cervical screening. RESULTS:HPV primary screening triage with p16/Ki-67 dual stain showed higher sensitivity without losing specificity compared to conventional Pap smear. The improving the screening performance leads to decrease the prevalence of precancerous lesion, annual incidence and mortality of cervical cancer. The incidence of cervical cancer case detected by new algorithm compared with conventional method were 31,607 and 38,927, respectively. In addition, the new algorithm was more effective and more costly (average QALY 24.03, annual cost $13,262,693) than conventional cytology (average QALY 23.98, annual cost $7,713,251). The incremental cost-effective ratio (ICER) per QALY gained was $1,395. The sensitivity analysis showed if the cost of cytology and HPV test increased three times, the ICER would fall to $303/QALY gained and increased to $4,970/QALY gained, respectively. CONCLUSION:Our model results suggest that screening by use of HPV genotyping test as a primary screening test combined with dual stain cytology as the triage of HPV positive women in Thai population 30-65 years old is expected to be more cost-effective than conventional Pap cytology.
| S-EPMC6393632 | biostudies-literature
Project description:Cervical cancer is one of the most common cancers in women and could be prevented by human papilloma virus (HPV) vaccination. Cervarix, the first available HPV vaccine, has been widely administrated to Chinese women, while little was known about its effect on the prevention and control for HPV related diseases in China. The study aims to assess the impact of Cervarix on HPV infection and cervical related diseases in real world. This is a prospective, multi-age birth cohort study to investigate the incidence and continuous status of HPV infection, and relevant cervical diseases by exposure status (with Cervarix vaccination history or without any HPV vaccination history). It is planned to recruit 12,118 eligible women at age of 9 to 45 years from vaccination clinics or hospital outpatient clinics, and then follow up them for three years. The standard questionnaire will be used to collect information such as demographic characteristics, menstruation and obstetrical histories, history of sexual behavior, personal behavior history, history of disease and pathogen infection, medication history, and family history at baseline. After three years, the changes of these behaviors will be investigated again, and other related health status information will be retrieved from the electronic health records during the follow-up period. If available physically and legally, the cervical cancer screening will be performed, including type-specific HPV deoxyribonucleic acid (DNA) polymerase chain reaction (PCR) testing and contingent thinprep cytologic test (TCT) and colposcopy. The free cervical cancer screening will be captured and uploaded timely to the Yinzhou Regional Health Information Platform (YRHIP); therefore, the long-term outcomes of participants will be monitored. This prospective cohort study will assess the impact of HPV vaccine on HPV infection and related cervical diseases in women aged 9-45 years, which makes up for the lack of evidence in Chinese women. The results of this study will provide support for understanding the impact of HPV vaccination in China, and make a contribution to increasing HPV vaccination and cervical cancer screening coverage in China. This study has been retrospectively registered on clinicaltrials.gov (NCT05341284) on April 22, 2022.
| S-EPMC9673205 | biostudies-literature
Project description:BackgroundWhile human papillomavirus (HPV) DNA testing offers high sensitivity for the detection of significant cervical disease, its specificity is suboptimal given the high prevalence of transient HPV infections (CIN1 or less). Biomarkers to identify those suffering from low grade disease from those with high grade disease could save healthcare costs and reduce patient anxiety.ObjectiveThe objective of the present work was to develop and test an immunohistochemistry (IHC)-based dual viral and cellular biomarker strategy which was applicable to liquid based cytology (LBC) samples.Study designWe developed a novel IHC assay for detection of HPV E4 and cellular minichromosome maintenance (MCM) proteins in routinely taken cervical LBC samples using cytospin-prepared slides. The assay was applied to a prospective cohort of Scottish women referred to a colposcopy clinic due to preceding cytological abnormalities. The performance of the biomarkers for detection of clinically insignificant (CIN1 or less) versus significant disease was determined.ResultsA total of 81 women were recruited representing 64 cases of <=CIN1 and 28 of CIN2?+?. Biomarker performance relative to histopathology outcomes showed high levels of MCM detection was significantly associated with CIN2+ (p?=?0.03) while E4 was detected more frequently in <=CIN1 (p?=?0.06).ConclusionsCombined detection of a host proliferation marker and a marker of viral gene expression could allow triage of cases of clinically insignificant disease prior to colposcopy. However, there was overlap between distributions of MCM levels in CIN2+ and <=CIN1 suggesting that additional biomarkers would be required for improved specificity. Combined with cytospin-prepared slides this approach could provide a means of risk stratification of disease in low resource settings.
| S-EPMC6224362 | biostudies-literature
Project description:BackgroundThe main goal of cervical screening programs is to detect and treat precancer before cancer develops. Human papillomavirus (HPV) testing is more sensitive than cytology for detecting precancer. However, reports of rare HPV-negative, cytology-positive cancers are motivating continued use of both tests (cotesting) despite increased testing costs.MethodsWe quantified the detection of cervical precancer and cancer by cotesting compared with HPV testing alone at Kaiser Permanente Northern California (KPNC), where 1?208?710 women age 30?years and older have undergone triennial cervical cotesting since 2003. Screening histories preceding cervical cancers (n?=?623) and precancers (n?=?5369) were examined to assess the relative contribution of the cytology and HPV test components in identifying cases. The performances of HPV testing and cytology were compared using contingency table methods, general estimating equation models, and nonparametric statistics; all statistical tests were two-sided.ResultsHPV testing identified more women subsequently diagnosed with cancer (P < .001) and precancer (P < .001) than cytology. HPV testing was statistically significantly more likely to be positive for cancer at any time point (P < .001), except within 12?months (P = .10). HPV-negative/cytology-positive results preceded only small fractions of cases of precancer (3.5%) and cancer (5.9%); these cancers were more likely to be regional or distant stage with squamous histopathology than other cases. Given the rarity of cancers among screened women, the contribution of cytology to screening translated to earlier detection of at most five cases per million women per year. Two-thirds (67.9%) of women found to have cancer during 10?years of follow-up at KPNC were detected by the first cotest performed.ConclusionsThe added sensitivity of cotesting vs HPV alone for detection of treatable cancer affected extremely few women.
| S-EPMC6279277 | biostudies-literature
Project description:Cervical cancer is the fourth most common type of cancer is women worldwide,and it is a major cause of cancer-related deaths in developing countries. Despite the marked reduction oberved in the rates of this disease as a result of screening programs, it is necessary to develop robust biomarkers that can detect the neoplastic early in HPV-related cervical leisons. We performed comparative mRNA seqeuncing from exfoliative cervical cytology from nine Korean women on the Illumina NovaSeq6000 platforms. The pathological tissues mathced to the corresponding cytological samples were simulanously confirmed and were considered to be endpoint diagnosis. The pathological dianoses consisted of three cases of chronic cervicitis, 2 high-grade squamous intraepithelial leisons(HSILs), 2squamous cell carcinomas in situ(CIS); and 2 invasive quamous cell carcinomas (SQCCs), respectively. Using bioinformatics analyses, differentially expressed genes (DEGs; absolute fold change >1; p<0.05) were applied for Gene Ontology (GO), Gene Set EnrichmentAnalysis (GSEA), and protein-protein interaction (PPI) networks.
2022-10-18 | GSE215744 | GEO