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Human Papillomavirus Same Genotype Persistence and Risk of Cervical Intraepithelial Neoplasia2+ Recurrence.

ABSTRACT: To evaluate the significance of HPV persistence as a predictor for the development of CIN2+ recurrence and the impact of multiple genotypes and of HPV 16/18 on recurrence risk. A prospective cohort observational study was carried out at the European Institute of Oncology, Milan, Italy, from December 2006 to December 2014. A total of 408 women surgically treated by excisional procedure for pre-neoplastic and neoplastic cervical lesions were enrolled. HPV test was performed at baseline and at first follow-up visit planned at 6 ± 3 months after treatment. Two-year cumulative incidences for relapse were estimated and compared by the Gray's test. Overall, 96 (23.5%) patients were persistent for at least one genotype at three to nine months from baseline and 21 (5.1%) patients relapsed. The two-year cumulative relapse incidence was higher in HPV persistent patients compared to not-persistent (CIF = 27.6%, 95% CI: 16.2-40.2% versus CIF = 1.7%, 95% CI: 0.3-5.8%, p < 0.001), in women with persistent multiple infections (CIF = 27.2%, 95% CI: 7.3-52.3%, p < 0.001), and with the persistence of at least one genotype between 16 and 18, irrespective of the presence of other HR genotypes (CIF = 32.7%, 95% CI: 17.9-48.3%, p < 0.001), but not significantly different from women positive for single infections or any other HR genotype, but not for 16 and 18. The risk of CIN2+ recurrence should not be underestimated when same HPV genotype infection persists after treatment.

SUBMITTER: Iacobone AD

PROVIDER: S-EPMC8345074 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Human Papillomavirus Same Genotype Persistence and Risk: A Systematic Review.

Project description:ObjectiveThe aim of the study was to examine whether high-grade cervical intraepithelial neoplasia (CIN) was more closely associated with human papillomavirus (HPV) same-genotype persistence (SGTP) versus clearance of prior infection with a subsequent infection by a new genotype (genotype switch [GS]), clearance of HPV infection, or acquisition of a new HPV infection after a negative infection status, during a follow-up testing subsequent to abnormal screening results.Materials and methodsMEDLINE, Cochrane Library, Health Technology Assessment, and clinicaltrials.gov were searched from January 2000 to July 2019 for prospective controlled trials and observational studies of women and retrospective studies using HPV assays with extended- or full-genotype reporting. The primary outcome was high-grade CIN after at least 2 rounds of testing. Overall quality of evidence for the risk estimate outcomes was assessed. Of the 830 identified abstracts, 66 full-text articles were reviewed, and 7 studies were included in the synthesis. The study protocol was registered with the PROSPERO International Prospective Register of Systematic Reviews (CRD42018091093).ResultsContinued HPV-positive women falls in 2 equally large groups: SGTP and GS. Sensitivity, positive predictive value, and positive likelihood ratio of SGTP were significantly higher than for GS. Human papillomavirus genotypes may be ranked into 3 tiers (immediate colposcopy, follow-up testing, return to routine screening), according to associated risk of persistence for high-grade CIN and to prevailing clinical action thresholds.ConclusionsThere is moderately high-quality evidence to support the clinical utility of SGTP to improve risk discrimination for high-grade CIN compared with qualitative HPV testing without genotype-specific information.

| S-EPMC7748037 | biostudies-literature

Human papillomavirus genotype-specific risks for cervical intraepithelial lesions.

Project description:Prevalence of different HPV genotypes is changing after HPV vaccination. The associated risks are needed for optimizing cervical cancer screening.To estimate HPV type-specific prevalence, odds ratio (OR), and positive predictive value (PPV) for cervical cytological abnormalities, we determined 41 different HPV genotypes in cervical samples from a population-based sample of 8351 women aged 18-51 years before HPV vaccination era (V501-033; NCT01077856).Prevalence of HPV16 was 4.9% (95% CI: 4.4-5.5) with the PPV for high-grade cytology 11.2%, and OR 11.9 (95% CI: 8.5-16.5). Carcinogenic HPVs included in the nonavalent vaccine (HPV16,18,31,33,45,52,58) had a population prevalence of 14.4% (95% CI: 13.5-15.4), with PPV of 8.0% (95% CI: 6.8-9.3) and OR 23.7 (95% CI: 16.0-63.5) for high-grade cytology. HPV types currently included in most screening tests, but not vaccinated against (HPV35,39,51,56,59,66,68) had a joint prevalence of 8.5% (95% CI: 7.8-9.2) with PPV of 4.4% (95% CI: 3.3-5.7) and OR of 2.9 (95% CI: 2.0-4.0) for high-grade cytology. The other 27 non-carcinogenic genotypes had a prevalence of 11.8%, PPV of 2.9% (95% CI:2.1-3.9), and OR 1.5 (95% CI: 1.1-2.2.) for high-grade cytology.These results suggest that HPV screening tests in the post-vaccination era might perform better if restricted to the HPV types in the nonavalent vaccine and screening for all 14 HPV types might result in suboptimal balance of harms and benefits.

| S-EPMC8018444 | biostudies-literature

Prevalence and Genotype Distribution of Human Papillomavirus in Invasive Cervical Cancer, Cervical Intraepithelial Neoplasia, and Asymptomatic Women in Southeast China.

Project description:Cervical cancer is one of the leading causes of cancer-related deaths among women and it is caused by the human papillomavirus (HPV). High variation has been reported in the attribution of specific HPV genotypes to cervical neoplasia among various geographic regions. For effective control of cervical cancer through HPV vaccination, it is essential to estimate the cost-effectiveness of vaccination, to monitor the potential transition into other HPV genotypes, and to understand the distribution of specific HPV genotypes across a specific geographic region. In this study, the distribution of HPV genotypes was investigated in southeast China, from 2011 to 2016. The 12,816 cervical swabs collected from women (age 18-78 years, median 43.6 years) outpatients were analyzed. HPV prevalence among 12,816 cervical swabs analyzed was 22.3% (2,856/12,816). Among these positive cases, 2,216 had only one HPV genotype while 640 had multiple HPV genotypes. The cases with multiple types revealed 23 different HPV genotypes with the five most prevalent being HPV18 (18.2%), HPV52 (14.1%), HPV16 (11.9%), HPV58 (10.6%), and HPV33 (5.5%). The rates of HPV infection in patients with cervical inflammation, CIN-1, CIN-2, CIN-3, squamous carcinoma, and adenocarcinoma were 38.4%, 80.5%, 82.6%, 92.3%, 97.5%, and 93.4%, respectively. Four HPV genotypes, HPV18, HPV16, HPV52, and HPV58, were more prevalent in patients with CIN-2-CIN-3 and invasive cervical cancer. A comparison of HPV genotypes attribution to cervical cancer between southeast China and global incidences revealed distinct differences. Due to this unique prevalence, it is essential to streamline the vaccination development protocol prior to administering vaccines based on global data.

| S-EPMC6196990 | biostudies-literature

Risk of human papillomavirus infection and cervical intraepithelial lesions in Chinese renal transplant recipients.

Project description:ObjectiveWhile human papillomavirus (HPV) infection in women is associated with cervical intraepithelial neoplasia and cervical cancer, HPV testing is not often performed in routine practice for renal transplantation patients. The genotype-specific prevalence of HPV and risk factors for HPV infection are still unclear.MethodsFrom 2010 to 2020, patients receiving renal transplantation surgery (referred to as RTRs), who had been screened for HPV infection one year after transplantation were enrolled. A comparison cohort of four age- and marital status-matched healthy individuals was selected for RTRs. The clinical characteristics and cervical screening results of RTRs were analyzed.ResultsOur study included 196 female renal transplant recipients (RTRs), none of whom had been vaccinated against HPV. Overall high-risk HPV (hrHPV) infection and abnormal cytology rates in the RTR group were 23.5% and 20.9%, respectively. The odds ratios of hrHPV infection and cervical intraepithelial neoplasia grade 2+ in RTRs vs. non-RTRs were 3.033 (95% CI, 2.013-4.568) and 3.628 (95% CI, 1.863-7.067), respectively. The prevalence of HPV16 in RTRs was much higher (30.4% vs. 8.3%, P=0.002). The multi-infection rate was much higher in HPV-infected RTRs (23.9% vs. 1.14%, P<0.001). The only risk factor for hrHPV infection was the duration of immunosuppression, which increased with time.ConclusionRTRs had significantly higher HPV infection rates and increased risks of HPV-related cervical premalignancies and cancers due to the immunosuppressed state. The duration of immunosuppression is a risk factor for transplant recipients. Female RTRs may benefit from more frequent cervical cancer screening after renal transplantation than healthy women. Prospective research on HPV infection dynamics in RTRs and optimal screening methods should be further explored in the future.

| S-EPMC9359460 | biostudies-literature

Chromosomal profiles of high-grade cervical intraepithelial neoplasia relate to duration of preceding high-risk human papillomavirus infection

Project description:High-grade cervical intraepithelial neoplasia (CIN2/3) represents a heterogeneous disease both with respect to clinical behaviour and chromosomal aberrations detected. We hypothesized that the extent of chromosomal aberrations reflects the duration of their existence. Chromosomal profiles were determined of CIN3 of women with a known 5 year history of high-risk human papillomavirus virus (hrHPV) infection, in which duration of prior hrHPV infection was considered a proxy for duration of CIN3 existence. Eleven women had a <5 year preceding hrHPV infection (CIN3<5yrPHI) and 24 had a PHI lasting ≥5 years (CIN3≥5yrPHI). For comparison, 6 CIN3 adjacent to squamous cell carcinomas (CIN3-SCC), the corresponding SCCs, and 6 CIN1 were included. Unsupervised hierarchical clustering analysis of the chromosomal profiles revealed two clusters. One was characterized by a low number of chromosomal aberrations and included all CIN1, 81.8% of CIN3<5yrPHI and 33.3% of CIN3≥5yrPHI. Samples in the second cluster, displaying multiple aberrations, included 18.2% of CIN3<5yrPHI, 66.7% CIN3≥5yrPHI, all except one CIN3-SCC and all SCCs. The number of genomic aberrations increased according to lesion grade and also with longer duration of PHI. The increase in aberrations in CIN3≥5yrPHI compared to <5yrPHI was highly significant (p=0.001), suggesting that CIN3≥5yrPHI represent more severe lesions. A longer duration of preceding hrHPV infection is associated with an increased number of chromosomal aberrations. Hence, CIN3 with a longer duration of existence are likely more prone to have an increased short-term risk of cervical cancer.

2012-01-25 | GSE30155 | GEO

Positive Surgical Margin, HPV Persistence, and Expression of Both TPX2 and PD-L1 Are Associated with Persistence/Recurrence of Cervical Intraepithelial Neoplasia after Cervical Conization.

Project description:ObjectiveTo determine the clinicopathologic and immunohistochemical predictors of the persistence/recurrence of cervical intraepithelial neoplasia (CIN) after cervical conization.MethodsMedical records of 502 patients who received cervical conization treatment of CIN between 2005 and 2012 were reviewed. The clinicopathologic parameters were analyzed using Cox hazard regression. Fifty patients with CIN persistence/recurrence were matched to 50 cases without CIN persistence/recurrence. These 100 cervical specimens were assessed for expression of insulin-like growth factor II messenger RNA (mRNA)-binding protein 3 (IMP3), targeting protein for xenopus kinesin-like protein 2 (TPX2), and programmed cell death-1 ligand-1 (PD-L1) using immunohistochemical staining.ResultsMultivariate analysis found that the independent predictors of CIN persistence/recurrence were positive surgical margin (hazard ratio 5.777, 95% confidence interval 2.334-14.301, p < 0.001) and human papilloma virus persistence for 6 months (hazard ratio 20.685, 95% confidence interval 7.350-57.657, p < 0.001). Co-expression of TPX2 and PD-L1 was significantly higher in CIN persistence/recurrence group than the group without CIN persistence/recurrence (p = 0.013). The depth of glandular involvement (GI) was less than 3mm in about 86.8% (59/68) CIN2-3 lesions, However, No statistically significant associations between GI and persistence/recurrence were observed (P = 0.58).ConclusionPositive surgical margin, HPV persistence, and expression of both TPX2 and PD-L1 are associated with persistence/recurrence of cervical intraepithelial neoplasia after cervical conization.

| S-EPMC4666599 | biostudies-literature

Test Accuracy of Human Papillomavirus in Urine for Detection of Cervical Intraepithelial Neoplasia.

Project description:The objective was to assess the diagnostic test accuracy of high-risk human papillomavirus (hrHPV) testing of self-collected urine and cervicovaginal samples for the detection of cervical intraepithelial neoplasia grade 2 or higher (CIN2+). We recruited a convenience sample of women 25 to 65 years of age who were undergoing clinically indicated colposcopy at two medical centers in North Carolina between November 2016 and January 2019. Women with normal cytology results and positive hrHPV results were also recruited. Urine samples, self-collected cervicovaginal samples, provider-collected cervical samples, and cervical biopsy samples were obtained from all enrolled women. Samples were tested for hrHPV DNA using the Onclarity assay (Becton Dickinson, Sparks, MD). Biopsy samples were histologically graded as CIN2+ or <CIN2. We calculated the sensitivity and specificity for detection of CIN2+ and assessed agreement between sample collection methods. We included 307 women (median age, 36 years) with valid histology results and triple-matched urine, self-collected cervicovaginal, and provider-collected cervical hrHPV results; 83 women (27%) had CIN2+. Urine-based hrHPV testing correctly identified 80% of CIN2+ cases (95% confidence interval [CI], 71 to 88%) using the PCR cycle threshold (CT ) established for provider-collected cervical samples, but sensitivity remained below the estimates for self-collected cervicovaginal and provider-collected cervical samples (both 94% [95% CI, 89 to 99%]). Using a higher CT cutoff value of ≤40, 90% sensitivity was achieved for urine-based hrHPV testing. Agreement between results for urine samples and self-collected cervicovaginal samples (kappa = 0.58) or provider-collected cervical samples (kappa = 0.54) was moderate. Urine-based hrHPV testing may be a promising approach to improve cervical cancer screening coverage, especially among women with limited access to health care.

| S-EPMC7041584 | biostudies-literature

Role of human papillomavirus status after conization for high-grade cervical intraepithelial neoplasia.

Project description:Human papillomavirus (HPV) is the well-established etiologic factor for cervical neoplasia. Cervical conization constitutes an effective treatment for high-grade cervical intraepithelial neoplasia (HG-CIN). We conducted an observational study for long-term outcomes and HPV genotype changes after conization for HG-CIN. Between 2008 and 2014, patients with newly diagnosed HG-CIN before conization (surveillance new [SN] group) and those who had undergone conization without hysterectomy (surveillance previous [SP] group) were enrolled. HPV testing and Pap smear were performed periodically for the SN and SP (collectively S) groups. All other patients receiving conization for HG-CIN during the study period were identified from our hospital database. Those eligible but not enrolled into our study were assigned to the non-surveillance (non-S) group. For the S group (n = 493), the median follow-up period was 74.3 months. Eighty-four cases had recurrent CIN Grade 2 or worse (CIN2+) (5-year cumulative rate: 14.8%), of which six had invasive cancer. Among the 84 patients, 65 (77.4%) exhibited type-specific persistence in the paired HPV results, whereas only 7 (8.3%) harbored new HPV types that belonged to the 9-valent vaccine types. Among the 7397 non-S patients, 789 demonstrated recurrent CIN2+, of which 57 had invasive cancer. The stages distribution of those progressed to invasive cancer in the non-S group were more advanced than the S group (P = .033). Active surveillance might reduce the severity of those progressed to cancer. Because a majority of the patients with recurrent CIN2+ had persistent type-specific HPV infections, effective therapeutic vaccines are an unmet medical need.

| S-EPMC7754315 | biostudies-literature

Persistence of cervical high-risk human papillomavirus in women living with HIV in Denmark - the SHADE.

Project description:BackgroundWomen living with HIV (WLWH) have high rates of persistent high-risk human papillomavirus (hrHPV) infections and cervical cancer. We aimed to assess the distribution of hrHPV genotypes, risk factors of type-specific hrHPV persistence, and high-grade squamous intraepithelial lesions or worse (≥HSIL) in WLWH in Denmark.MethodsFrom the prospective Study on HIV, cervical Abnormalities and infections in women in Denmark (SHADE) we identified WLWH with a positive hrHPV test during the study period; 2011-2014. HIV demographics were retrieved from the Danish HIV Cohort Study and pathology results from the The Danish Pathology Data Bank. Logistic regression was used to identify risk factors associated with persistent hrHPV infection (positivity of the same hrHPV type in two samples one-two years after the first hrHPV positive date) and ≥ HSIL.ResultsOf 71 WLWH, 31 (43.7%) had persistent hrHPV infection. Predominant hrHPV genotypes were HPV58, 52, 51, and 35 and most frequently observed persistent genotypes were HPV52, 33 and 31. CD4 < 350 cells/μL predicted genotype-specific hrHPV persistence (adjusted OR 4.36 (95%CI: 1.18-16.04)) and ≥ HSIL was predicted by prior AIDS (adjusted OR 8.55 (95% CI 1.21-60.28)).ConclusionsThis prospective cohort study of well-treated WLWH in Denmark found a high rate of persistent hrHPV infections with predominantly non-16/18 hrHPV genotypes. CD4 count < 350 cells/μL predicted hrHPV persistence, while prior AIDS predicted ≥HSIL.

| S-EPMC6706931 | biostudies-literature

Distribution of human papillomavirus genotypes in women with high-grade cervical intraepithelial lesions and cervical carcinoma and analysis of human papillomavirus-16 genomic variants.

Project description:AimTo analyze the distribution of high-risk human papillomavirus (HR-HPV) genotypes and the diversity of HPV-16 genomic variants in Croatian women with high-grade squamous intraepithelial lesions (HSIL) and cervical carcinoma.MethodsTissue biopsy specimens were obtained from 324 women with histopathologically confirmed HSIL or cervical carcinoma, 5 women with low-grade SIL, and 49 women with negative histopathology. HR-HPV DNA was detected with Ampliquality HPV-type nucleic-acid hybridization assay, which identifies 29 different HPV genotypes. HPV-16 genomic variants were analyzed by an in-house sequencing.ResultsThe most common HPV type in women with HSIL was HPV-16, detected in 127/219 (57.9%) specimens. HPV-16 was also the dominant type in squamous cell cervical carcinoma (46/69 or 66.7%) and in adenocarcinoma (18/36 or 50.0%). Out of 378 patients, 360 had HR-HPV (282 single infections and 79 multiple infections), 3 (0.8%) patients had low-risk HPV, and 15 (4%) tested negative. HPV-16 variants were determined in 130 HPV-16 positive specimens, including 74 HSIL and 46 carcinoma specimens. In HSIL specimens, 41 distinct variants were found, 98.6% belonging to the European branch and 1.4% belonging to the African branch. In cervical carcinoma specimens, 95% isolates grouped in 41 variants belonging to the European branch, one isolate (2.5%) belonged to the North American, and one (2.5%) to the Asian-American branch.ConclusionHPV-16, mainly belonging to the European branch, was the most frequent HPV genotype in women from Croatia with histologically confirmed HSIL and cervical cancer.

| S-EPMC7976879 | biostudies-literature

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