Data on human papillomavirus (HPV) type-specific cervical cancer risk in women living with human immunodeficiency virus (WLHIV) are needed to understand HPV⁻HIV interaction and to inform prevention ...programs for this population. We assessed high-risk HPV type-specific prevalence in cervical samples from 463 WLHIV from South Africa with different underlying, histologically confirmed stages of cervical disease. Secondly, we investigated DNA hypermethylation of host cell genes
,
, and
, as markers of advanced cervical disease, in relation to type-specific HPV infection. Overall, HPV prevalence was 56% and positivity increased with severity of cervical disease: from 28.0% in cervical intraepithelial neoplasia (CIN) grade 1 or less (≤CIN1) to 100% in invasive cervical cancer (ICC). HPV16 was the most prevalent type, accounting for 9.9% of HPV-positive ≤CIN1, 14.3% of CIN2, 31.7% of CIN3, and 45.5% of ICC. HPV16 was significantly more associated with ICC and CIN3 than with ≤CIN1 (adjusted for age, OR
7.36 (95% CI 2.33⁻23.21) and 4.37 (95% CI 1.81⁻10.58), respectively), as opposed to non-16 high-risk HPV types. Methylation levels of
,
, and
in cervical scrapes of women with CIN3 or worse (CIN3+) associated with HPV16 were significantly higher compared with methylation levels in cervical scrapes of women with CIN3+ associated with non-16 high-risk HPV types (
-values 0.017, 0.019, and 0.026, respectively). When CIN3 and ICC were analysed separately, the same trend was observed, but the differences were not significant. Our results confirm the key role that HPV16 plays in uterine cervix carcinogenesis, and suggest that the evaluation of host cell gene methylation levels may monitor the progression of cervical neoplasms also in WLHIV.
Type-specific high-risk HPV (hrHPV) infection is related to cervical carcinogenesis. The prevalence of hrHPV infection varies geographically, which might reflect the epidemiological characteristics ...of cervical cancer among different populations. To establish a foundation for HPV-based screening and vaccination programs in China, we investigated the most recent HPV prevalence and genotypic distributions in different female age groups and geographical regions in China.
In 2012, a total of 120,772 liquid-based cytological samples from women enrolled for population- or employee-based cervical screening in 37 Chinese cities were obtained by the Laboratory of Molecular Infectious Diseases of Guangzhou KingMed. A total of 111,131 samples were tested by Hybrid Capture II and the other 9,641 were genotyped using the Tellgenplex™ HPV DNA Assay.
The total positive rate for hrHPV was 21.07 %, which ranged from 18.42 % (Nanchang) to 31.94 % (Haikou) and varied by region. The regions of Nanchang, Changsha, Hangzhou, Chengdu, Fuzhou, Guangdong, and Guiyang could be considered the low prevalence regions. Age-specific prevalence showed a "two-peak" pattern, with the youngest age group (15-19 years) presenting the highest hrHPV infection rate (30.55 %), followed by a second peak for the 50-60-year-old group. Overall, the most prevalent genotypes were HPV16 (4.82 %) and HPV52 (4.52 %), followed by HPV58 (2.74 %). Two genotypes HPV6 (4.01 %) and HPV11 (2.29 %) were predominant in the low-risk HPV (lrHPV) type, while the mixed genotypes HPV16 + 52 and HPV52 + 58 were most common in women with multiple infections.
This study shows that HPV infection in China has increased to the level of an "HPV-heavy-burden" zone in certain regions, with prevalence varying significantly among different ages and regions. Data from this study represent the most current survey of the nationwide prevalence of HPV infection in China, and can serve as valuable reference to guide nationwide cervical cancer screening and HPV vaccination programs.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Methylation of viral DNA has been proposed as a novel biomarker for triage of human papillomavirus (HPV) positive women at screening. This systematic review and meta-analysis aims to assess how ...methylation levels change with disease severity and to determine diagnostic test accuracy (DTA) in detecting high-grade cervical intra-epithelial neoplasia (CIN).
We performed searches in MEDLINE, EMBASE and CENTRAL from inception to October 2019. Studies were eligible if they explored HPV methylation levels in HPV positive women. Data were extracted in duplicate and requested from authors where necessary. Random-effects models and a bivariate mixed-effects binary regression model were applied to determine pooled effect estimates.
44 studies with 8819 high-risk HPV positive women were eligible. The pooled estimates for positive methylation rate in HPV16 L1 gene were higher for high-grade CIN (≥CIN2/high-grade squamous intra-epithelial lesion (HSIL) (95% confidence interval (95%CI:72·7% (47·8–92·2))) vs. low-grade CIN (≤CIN1/low-grade squamous intra-epithelial lesion (LSIL) (44·4% (95%CI:16·0–74·1))). Pooled difference in mean methylation level was significantly higher in ≥CIN2/HSIL vs. ≤CIN1/LSIL for HPV16 L1 (11·3% (95%CI:6·5–16·1)). Pooled odds ratio of HPV16 L1 methylation was 5·5 (95%CI:3·5–8·5) for ≥CIN2/HSIL vs. ≤CIN1/LSIL (p < 0·0001). HPV16 L1/L2 genes performed best in predicting CIN2 or worse (pooled sensitivity 77% (95%CI:63–87), specificity 64% (95%CI:55–71), area under the curve (0·73 (95%CI:0·69–0·77)).
Higher HPV methylation is associated with increased disease severity, whilst HPV16 L1/L2 genes demonstrated high diagnostic accuracy to detect high-grade CIN in HPV16 positive women. Direct clinical use is limited by the need for a multi-genotype and standardised assays. Next-generation multiplex HPV sequencing assays are under development and allow potential for rapid, automated and low-cost methylation testing.
NIHR, Genesis Research Trust, Imperial Healthcare Charity, Wellcome Trust NIHR Imperial BRC, European Union's Horizon 2020
Dynamic Spectral Imaging System (DySIS)map (DySIS Medical Ltd, Edinburgh, UK) and ZedScan (Zilico Limited, Manchester, UK) can be used adjunctively with conventional colposcopy, which may improve the ...detection of cervical intraepithelial neoplasia (CIN) and cancer.
To systematically review the evidence on the diagnostic accuracy, clinical effectiveness and implementation of DySISmap and ZedScan as adjuncts to standard colposcopy, and to develop a cost-effectiveness model.
Four parallel systematic reviews were performed on diagnostic accuracy, clinical effectiveness issues, implementation and economic analyses. In January 2017 we searched databases (including MEDLINE and EMBASE) for studies in which DySISmap or ZedScan was used adjunctively with standard colposcopy to detect CIN or cancer in women referred to colposcopy. Risk of bias was assessed with the Quality Assessment of Diagnostic Accuracy Studies (QUADAS)-2 tool. Summary estimates of diagnostic accuracy were calculated using bivariate and other regression models when appropriate. Other outcomes were synthesised narratively. A patient-level state-transition model was developed to evaluate the cost-effectiveness of DySISmap and ZedScan under either human papillomavirus (HPV) triage or the HPV primary screening algorithm. The model included two types of clinics 'see and treat' and 'watchful waiting' (i.e. treat later after confirmatory biopsy), as well as the reason for referral (low-grade or high-grade cytological smear). Sensitivity and scenario analyses were undertaken.
Eleven studies were included in the diagnostic review (nine of DySISmap and two of ZedScan), three were included in the clinical effectiveness review (two of DySISmap and one of ZedScan) and five were included in the implementation review (four of DySISmap and one of ZedScan). Adjunctive DySISmap use was found to have a higher sensitivity for detecting CIN grade 2+ (CIN 2+) lesions 81.25%, 95% confidence interval (CI) 72.2% to 87.9% than standard colposcopy alone (57.91%, 95% CI 47.2% to 67.9%), but with a lower specificity (70.40%, 95% CI 59.4% to 79.5%) than colposcopy (87.41%, 95% CI 81.7% to 91.5%). (Confidential information has been removed.) The base-case cost-effectiveness results showed that adjunctive DySISmap routinely dominated standard colposcopy (it was less costly and more effective). The only exception was for high-grade referrals in a watchful-waiting clinic setting. The incremental cost-effectiveness ratio for ZedScan varied between £272 and £4922 per quality-adjusted life-year. ZedScan also dominated colposcopy alone for high-grade referrals in see-and-treat clinics. These findings appeared to be robust to a wide range of sensitivity and scenario analyses.
All but one study was rated as being at a high risk of bias. There was no evidence directly comparing ZedScan with standard colposcopy. No studies directly compared DySIS and ZedScan.
The use of adjunctive DySIS increases the sensitivity for detecting CIN 2+, so it increases the number of high-grade CIN cases that are detected. However, it also reduces specificity, so that more women with no or low-grade CIN will be incorrectly judged as possibly having high-grade CIN. The evidence for ZedScan was limited, but it appears to increase sensitivity and decrease specificity compared with colposcopy alone. The cost-effectiveness of both adjunctive technologies compared with standard colposcopy, under both the HPV triage and primary screening algorithms, appears to be favourable when compared with the conventional thresholds used to determine value in the NHS.
More diagnostic accuracy studies of ZedScan are needed, as are studies assessing the diagnostic accuracy for women referred to colposcopy as part of the HPV primary screening programme.
This study is registered as PROSPERO CRD42017054515.
The National Institute for Health Research Health Technology Assessment programme.
We compared test sensitivity (in terms of prevented cancers) and overdiagnosis (in terms of non‐progressive pre‐invasive lesions) between the human papillomavirus test (HPV test, Hybrid Capture 2) ...and the traditional Pap test in routine screening for cervical cancer. The design was a randomised (1:1) health services study in Finland with intake between 2003 and 2007. We estimated sensitivity by the incidence method within one screening round. Overdiagnosis was based on the rate of cervical intraepithelial Grade 3 (CIN3) lesions diagnosed at screen and during the following interval. Out of 203,788 randomised women 132,298 attended (65% in both study arms) and 600,753 person‐years accumulated among attenders up to the end of 2010. In all attenders, 34 invasive cervical cancers and 288 CIN3 lesions were diagnosed at screen or during the following interval. The interval cancer incidence was 2.5/105 person‐years (sensitivity 0.87) and 1.4 (sensitivity 0.93) in the HPV arm and Pap test arm, respectively. The rate of CIN3 lesions was 57.1 and 38.8, respectively. In conclusion, sensitivity of HPV testing was similar to that of Pap testing but caused more overdiagnosis. Therefore, implementation of HPV testing needs to be reconsidered especially in countries with well organised programmes.
What's new?
Cervical cancer screeningresults in both benefit for preventing lesions from progressing to invasive cancer and harm for also detecting lesions that would never have led to invasive cancers. This randomised study compares the HPV test to the traditional Pap test in terms of sensitivity (detection of progressive lesions) and overdiagnosis (detection of non‐progressive lesions).While the HPV test is known to detect a higher number of pre‐invasive lesions, the authors found that sensitivity was high with both tests but overdiagnosis more common with the HPV test, suggesting the need to reconsider the implementation of HPV testing.
Abstract Objective To assess how the proportion of the cervical volume/length removed during treatment for cervical intraepithelial neoplasia (CIN) varies and whether this correlates to the pregnancy ...duration at delivery. Methods The present prospective observational study included 142 women undergoing CIN treatment at a university hospital during 2009–2013. The pretreatment and post-treatment cervical dimensions and cone size were measured with magnetic resonance imaging, three-dimensional transvaginal ultrasonography, or two-dimensional transvaginal ultrasonography, and the correlation between pregnancy outcomes and the relative proportion of the cervix excised was assessed. Results Pretreatment cervical volumes and cone volumes varied substantially (range 11–40 cm3 and 0.6–8 cm3 , respectively). The proportion of the volume excised ranged from 2.2% to 39.4%. Sixteen (11%) women conceived following treatment; 12 had a live birth (seven at term, three preterm). The pregnancy duration at delivery was significantly correlated with the proportion of the cervical volume ( r = –0.9; P < 0.001) and length ( r = –0.7; P = 0.01) excised and the cone volume ( r = –0.6; P = 0.04). Conclusion The pretreatment cervical dimensions and the proportions of the volume/length excised vary substantially, and the latter correlates with the pregnancy duration. Assessment of the proportion excised might help to stratify women at risk who need intensive surveillance when pregnant.
This study evaluates the feasibility and performance of careHPV, a novel human papillomavirus (HPV) DNA test, when used for screening women for cervical cancer in low-resource settings.
...Clinician-collected (cervical) and self-collected (vaginal) careHPV specimens, visual inspection with acetic acid (VIA), and Papanicolaou test were evaluated among 16,951 eligible women in India, Nicaragua, and Uganda. Women with positive screening results received colposcopy and histologic follow-up as indicated. The positivity of each screening method was calculated overall, by site, and age. In addition, the clinical performance of each screening test was determined for detection of cervical intraepithelial neoplasia (CIN) grade 2 (CIN2+) and CIN grade 3.
Moderate or severe dysplasia or cancer (taken together as CIN2+) was diagnosed in 286 women. The positivity rate ranged between 2.4% to 19.6% for vaginal careHPV, 2.9% to 20.2% for cervical careHPV, 5.5% to 34.4% for VIA, and 2.8% to 51.8% for Papanicolaou test. Cervical careHPV was the most sensitive for CIN2+ (81.5%; 95% confidence interval CI, 76.5-85.8) and CIN grade 3 (85.3%; 95% CI, 78.6-90.6) at all sites, followed by vaginal careHPV (69.6% and 71.3%, respectively). The sensitivity of VIA ranged from 21.9% to 73.6% and Papanicolaou test from 40.7% to 73.7%. The pooled specificities of cervical careHPV, vaginal careHPV, VIA, and Papanicolaou test were 91.6%, 90.6%, 84.2%, and 87.7%, respectively.
careHPV performed well in large multicountry demonstration studies conducted in resource-limited settings that have not previously been conducted this type of testing; its sensitivity using cervical samples or vaginal self-collected samples was better than VIA or Papanicolaou test. The feasibility of using careHPV in self-collected vaginal samples opens the possibility of increasing coverage and early detection in resource-constrained areas.
Large-scale data on type-specific HPV prevalences and disease burden are needed to monitor the impact of HPV vaccination and to plan for HPV-based cervical screening.
33 043 women (aged 25-65) were ...screened for HPV by a Hybrid Capture 2 (HC2) in a population-based programme. HPV-positive women (n=2574) were triaged by cytology and HPV genotyped using PCR-Luminex. Type-specific prevalence of HPV infection and its correlation to findings in cytology triage and histology as well as Population Attributable Fractions for a referral to colposcopy and findings in histology were calculated.
Among HC2-positive women, 61.5% had normal, 23.1% had ASC-US and 15.5% had LSIL or more severe (LSIL+) results in cytology. Out of HC2-positive samples, 57% contained the 13 Group 1/2A HPV types, which were targeted by the HC2, 15% contained Group 2B types, 8.5% Group 3 types and 30% were found to be negative in HPV genotyping. The proportion of samples positive for HPV by the HC2, but negative in HPV genotyping increased with age and decreased with increasing cytological abnormality. The most frequent types were HPV 16 (0.9% of screened women and 12.1% of the HC2-positive women), HPV 31 (0.7% and 8.9%, respectively) and HPV 52 (0.5% and 6.3%, respectively). The prevalence of Group 1/2A HPV types increased with increasing CIN grade and attributed 78.3% (95% CI 53.4-89.9) of the CIN 3+ lesions, while HPV 16 attributed 55.8% (40.0-67.5) of them.
The type-specific prevalence of HPV were slightly lower than the average in international meta-analyses. Genotyping for HPV 16 better identified women with CIN 3+ than cytology triage at the threshold of LSIL+. The high proportion of women that were HC2-positive but HPV-negative in genotyping suggests that HPV genotyping may be useful also for validation of results in HPV screening. The large-scale HPV genotyping data were found to be directly useful for planning further preventive efforts for cervical cancer.
Abstract Objective The present study was conducted to examine the value of screening for high-risk HPV in post-menopausal women. Methods A cohort of post-menopausal women ( n = 2113), age range 55–76 ...years, from Uppsala County, Sweden, were offered testing for both high-risk HPV and a Pap smear in the gynaecological screening during 2008–2010. For the HPV test the cervical smear sample was applied to a filter paper matrix, an indicating FTA elute card and HPV typing performed using a real-time PCR assay. Histological verified CIN2+ lesion was used as an end-point measurement. Results High-risk HPV were found in 6.2% (95% CI 5.2–7.3%) of the women ( n = 130) and 22% (95% CI 14–32%) ( n = 17) of these had CIN2+ lesions based on histology. The Pap smear taken in conjunction with the HPV test was abnormal in 9.7% (95% CI 5.7–16.3%) ( n = 12) of HPV positive women. Among HPV positive women with an abnormal Pap smear, the frequency of histology verified CIN2+ lesions was 67% (95% CI 38–86%) ( n = 8), as compared to 14% (95% CI 7–24%) ( n = 9) in HPV positive women with a normal smear. The prevalence of HPV16 in CIN2+ lesions (29%, 95% CI 22–37%) in post-menopausal women was less than half of previous estimates in pre-menopausal women from this population. Conclusions Most histological CIN2+ lesions in post-menopausal women are not recognized by a single Pap smear. A large fraction of pre-invasive cervical cancer cases in post-menopausal women result from infections by HPV types not included in the present vaccine formulas.
Objective
To determine the prevalence and predictors of precancerous cervical lesions among HIV‐positive women in Jos, Nigeria.
Methods
A cross‐sectional study was conducted from October 2017 to ...January 2018 among 326 HIV‐positive women. Cervical smears were collected for examination at the AIDS Preventive Initiative of Nigeria clinics of Jos University Teaching Hospital (JUTH) and Bingham University Teaching Hospital (BhUTH), Jos, Nigeria. Demographic characteristics of participants were documented using a structured questionnaire. Data were entered and analyzed using SPSS version 21.
Results
Of the 326 participants, precancerous cervical lesions were present in 40 (12.2%) women: 4 (1.2%) had atypical squamous cells of undetermined significance, 19 (5.8%) had low‐grade squamous intraepithelial lesions, 1 (0.3%) had atypical squamous cells cannot exclude high‐grade squamous intraepithelial lesions, 13 (4.0%) had high‐grade squamous intraepithelial lesions, and 3 (0.9%) had high‐grade squamous intraepithelial lesions, suspected for invasion. The multivariate logistics regression model showed that parity (odds ratio 3.4, 95% confidence interval 1.3–9.5, P=0.043) was a significant predictor of precancerous cervical lesions.
Conclusion
The prevalence of precancerous cervical lesions among HIV‐infected women is relatively low compared to earlier reported prevalence in an HIV population in Jos. Increasing parity was a significant predictor.
Age and parity were found to be significant predictors of precancerous cervical lesions after performing cervical smears and documenting demographic characteristics.
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