Population-based e-records to evaluate HPV triage of screen-detected atypical squamous cervical lesions in Catalonia, Spain, 2010-15

Equivocal lesions (ASC-US) are common abnormalities in cervical cancer screening exams. HPV testing helps to stratify the risk of progression to high-grade squamous intraepithelial lesions or more (HSIL+). Population-based medical electronic data can be used to evaluate screening recommendations. The study uses routine electronic data from primary health centers to estimate the impact of HPV testing in a 3-and a 5-year risk of HSIL+ after an ASC-US. The study includes data derived from medical electronic information from 85,775 women who first attended a cervical cancer screening visit at the National Health System facilities of Catalonia, Spain, during 2010-11 and followed up to 2015. Included women were aged between 25-65 years old, having at least one follow-up visit, and a cervical cytology of ASC-US (N = 1,647). Women with a first result of low-grade squamous intraepithelial lesions (LSIL) (N = 945) or those with negative cytology (N = 83,183) were included for comparison. Those with a baseline HSIL+ were excluded. Incident HSIL+ was evaluated by means of Kaplan-Meier curves and multivariate regression models. HPV test results were available for 63.4% of women with a baseline ASC-US. Among all ASC-US, 70 incident HSIL+ were identified at 5 years. ASC-US HPV positive women had a high risk of HSIL+ compared to women with negative cytology (adjusted HR = 32.7; 95% CI: 23.6-45.2) and a similar risk to women with baseline LSIL (HR = 29.3; 95% CI: 22.4-38.2), whereas ASC-US HPV negative women had no differential risk to that observed in baseline negative cytology. Women with ASC-US and no HPV test had an average HSIL+ risk (HR = 14.8; 95% CI: 9.7-22.5). Population-based e-medical records derived from primary health care centers allowed monitoring of screening recommendations, providing robust estimates for the study outcomes. This analysis confirms that HPV testing improved risk stratification of ASC-US lesions. The information can be used to improve diagnosis and management of screen detected lesions

Association of antiretroviral therapy with high-risk human papillomavirus, cervical intraepithelial neoplasia, and invasive cervical cancer in women living with HIV: a systematic review and meta-analysis.

BACKGROUND: The interactions between antiretroviral therapy (ART) and high-risk human papillomavirus (HPV) and cervical lesions in women living with HIV are poorly understood. We reviewed the association of ART with these outcomes. METHODS: We did a systematic review and meta-analysis by searching MEDLINE and Embase databases for cross-sectional or cohort studies published in English between Jan 1, 1996, and May 6, 2017, which reported the association of ART with prevalence of high-risk HPV or prevalence, incidence, progression, or regression of histological or cytological cervical abnormalities, or incidence of invasive cervcal cancer. Studies were eligible if they reported the association of combination ART or highly active ART use with the following outcomes: high-risk HPV prevalence; squamous intraepithelial lesion (SIL) or cervical intraepithelial neoplasia (CIN) prevalence, incidence, progression, or regression; and invasive cervical cancer incidence among women living with HIV. We did random-effects meta-analyses to estimate summary statistics. We examined heterogeneity with the I2 statistic. This review is registered on the PROSPERO database at the Centre of Reviews and Dissemination, University of York, York, UK (registration number CRD42016039546). FINDINGS: We identified 31 studies of the association of ART with prevalence of high-risk HPV (6537 women living with HIV) and high grade cervical lesions (HSIL-CIN2+; 9288 women living with HIV). Women living with HIV on ART had lower prevalence of high-risk HPV than did those not on ART (adjusted odds ratio [aOR] 0·83, 95% CI 0·70-0·99; I2=51%, adjusted for CD4 cell count and ART duration), and there was some evidence of association with HSIL-CIN2+ (0·65, 0·40-1·06; I2=30%). 17 studies reported the association of ART with longitudinal cervical lesion outcomes. ART was associated with a decreased risk of HSIL-CIN2+ incidence among 1830 women living with HIV (0·59, 0·40-0·87; I2=0%), SIL progression among 6212 women living with HIV (adjusted hazard ratio [aHR] 0·64, 95% CI 0·54-0·75; I2=18%), and increased likelihood of SIL or CIN regression among 5261 women living with HIV (1·54, 1·30-1·82; I2=0%). In three studies among 15 846 women living with HIV, ART was associated with a reduction in invasive cervical cancer incidence (crude HR 0·40, 95% CI 0·18-0·87, I2=33%). INTERPRETATION: Early ART initiation and sustained adherence is likely to reduce incidence and progression of SIL and CIN and ultimately incidence of invasive cervical cancer. Future cohort studies should aim to confirm this possible effect. FUNDING: UK Medical Research Council

Risk of malignant lymphoma associated with human herpesvirus-8: a case–control study in Spain

No overall increased risk of lymphoma associated with antibodies to human herpesvirus-8 was found in 526 lymphomas and 599 controls (odds ratio (OR)=1.04, 95% confidence interval (CI)=0.62-1.75); significant increases were noted for 19 lymphoplasmacytic lymphomas (OR=4.47, 95% CI=1.34-14.85) and nine low-grade lymphoma/lymphoma B-cell NOS (OR=5.82, 95% CI=1.07-31.73)

Does lowering the screening age for cervical cancer in The Netherlands make sense?\ud

Recommendations for the age to initiate cervical cancer screening should be directed towards maximum detection of early cervical cancer. However, the screening programme should do more good than harm. The aim of this analysis was to determine whether the target age for cervical cancer screening should be lowered in view of apparent increases in new cases of invasive cancer below age 30 and in age group 30–44 years in The Netherlands. Therefore, all cervical cancer cases diagnosed between January 1, 1989 and December 31, 2003 were selected from the nationwide population-based Netherlands Cancer Registry. For age group 25–39 years, incidence data were also available for 2004 and 2005. To describe trends, the estimated annual percentage of change and joinpoint analysis were used. Between ages 25 and 28 years, the absolute number of new cases of cervical cancer annually has varied between 0 and 9 per age. Significantly decreasing trends in incidence were observed for age groups 35–39 and 45–49 (p < 0.0001 and p = 0.01, respectively). The annual number of deaths fluctuated with a decreasing trend for age groups 30–34 and 35–39 years (p = 0.01 and p = 0.03, respectively). Because the incidence and mortality rates for cervical cancer among women younger than 30 are low and not increasing, lowering the age for cervical cancer screening is not useful at this time. Although the number of years of life gained is high for every case of cervical cancer prevented, the disadvantages of lowering the screening age would be very large and even become disproportionate compared to the potential advantage

Pediatric vulvar squamous cell carcinoma in a liver transplantation recipient: a case report

Here we report the first Korean case of a girl who developed noninvasive squamous cell carcinoma of the vulva at the age of 16 years. She was taking tacrolimus, an immunosuppressive agent, after living-related liver transplantation. The vulvar masses were microscopically proved as vulvar intraepithelial neoplasm II and III, even squamous cell carcinoma in situ. Human papillomavirus subtypes (69 and 73) and human papillomavirus types (66, 70, 73, and 43) were detected in the vulvar mass and the cervicovaginal smear, respectively. The outcome of liver transplantation for children has been markedly improved during the last several decades. However, the present case highlights the need to perform periodic genital examinations for the adolescents after liver transplantation. In addition to the high risk and probable high subtypes, uncommonly found human papillomavirus subtypes were extracted from her vulvar cancer. The present case is the first to show the possible relationship between previously unknown and uncommon human papillomavirus subtypes and pediatric post-transplant vulvar squamous cell carcinoma. More attention should be paid to the vulvar and cervical surveillance of pediatric transplant recipients by both medical specialists and general physicians

Antiretroviral Therapy and Detection of High-grade Cervical Intraepithelial Neoplasia (CIN2+) at Post-CIN Management Follow-up Among Women Living With Human Immunodeficiency Virus: A Systematic Review and Meta-Analysis.

BACKGROUND: We evaluated the association of antiretroviral therapy (ART), CD4+ count and human immunodeficiency virus (HIV) plasma viral load (PVL) on high-grade cervical intraepithelial neoplasia (CIN2+) detection at follow-up after CIN management among women living with HIV (WLHIV). METHODS: Medline, Embase, Global Health, and PubMed were searched from 1 January 1996 to 15 January 2020. Eligible studies investigated the association of ART, CD4+ count, or HIV PVL on histology-confirmed CIN2+ detection at follow-up. Summary estimates were obtained using random-effects meta-analyses; heterogeneity was examined using I2 statistic. PROSPERO registration: CRD42018115631. RESULTS: Eight studies representing 9 populations were identified, including 1452 WLHIV followed between 6 and 33 months post-CIN management. Pooled data from 8 populations (n = 1408) suggested weak evidence of a decreased risk of CIN2+ detection at follow-up among ART users compared to ART-naive women (crude odds ratio [cOR] = 0.70, 95% confidence interval [CI]: .36-1.36; I2 = 64.5%, P = .006; adjusted risk ratio [aRR] from 3 studies = 0.66, 95% CI: .20-2.24; I2 = 78.7%, P = .009). A significant association was observed in high-income countries (cOR = 0.24, 95% CI: .13-.45; I2 = 0.0%, P = .77) but not in low and middle-income countries (cOR = 1.13, 95% CI: .67-1.92; I2 = 18.8%, P = .30).In 3 populations, ART users with HIV PVL <50 copies/ml were less likely to have CIN2+ detection at follow-up (vs ≥50 copies/mL: cOR = 0.55, 95% CI: .32-.94; I2 = 0.0%, P = .23).There was weak evidence of decreased CIN2+ detection at follow-up among WLHIV with higher contemporary CD4+ cell counts (≥200 cells/µL vs <200 cells/µL [cOR = 0.36, 95% CI: .04-3.13; I2 = 81.3%, P = .021]) and significant evidence among women with a higher nadir CD4+ count (≥350 cells/µl vs <200 cells/µl [adjusted hazard ratio [aHR] = 0.35, 95% CI: .15-.84; I2 = 0%, P = .64]). CONCLUSION: ART may reduce the risk of CIN2+ detection at follow-up; this effect is most likely enhanced by a combination of adequate HIV control and excisional CIN treatment. Our findings support recommendations of early ART and the integration of CIN2+ screening and management into HIV care

Cervical cancer screening programmes and age-specific coverage estimates for 202 countries and territories worldwide: a review and synthetic analysis

Q1Q1Background: Cervical cancer screening coverage is a key monitoring indicator of the WHO cervical cancer elimination plan. We present global, regional, and national cervical screening coverage estimates against the backdrop of the 70% coverage target set by WHO. Methods: In this review and synthetic analysis, we searched scientific literature, government websites, and official documentation to identify official national recommendations and coverage data for cervical cancer screening for the 194 WHO member states and eight associated countries and territories published from database inception until Oct 30, 2020, supplemented with a formal WHO country consultation from Nov 27, 2020, to Feb 12, 2021. We extracted data on the year of introduction of recommendations, the existence of individual invitation to participate, financing of screening tests, primary screening and triage tests used, recommended ages and screening intervals, use of selfsampling, and use of screen-and-treat approaches. We also collected coverage data, either administrative or surveybased, as disaggregated as possible by age and for any available screening interval. According to data completeness and representativeness, different statistical models were developed to produce national age-specific coverages by screening interval, which were transformed into single-age datapoints. Missing data were imputed. Estimates were applied to the 2019 population and aggregated by region and income level. Findings: We identified recommendations for cervical screening in 139 (69%) of 202 countries and territories. Cytology was the primary screening test in 109 (78%) of 139 countries. 48 (35%) of 139 countries recommended primary HPV-based screening. Visual inspection with acetic acid was the most recommended test in resource-limited settings. Estimated worldwide coverage in women aged 30–49 years in 2019 was 15% in the previous year, 28% in the previous 3 years, and 32% in the previous 5 years, and 36% ever in lifetime. An estimated 1·6 billion (67%) of 2·3 billion women aged 20–70 years, including 662 million (64%) of 1·0 billion women aged 30–49 years, had never been screened for cervical cancer. 133 million (84%) of 158 million women aged 30–49 years living in high-income countries had been screened ever in lifetime, compared with 194 million (48%) of 404 million women in upper-middle-income countries, 34 million (9%) of 397 million women in lower-middle-income countries, and 8 million (11%) of 74 million in low-income countries. Interpretation: Two in three women aged 30–49 years have never been screened for cervical cancer. Roll-out of screening is very low in low-income and middle-income countries, where the burden of disease is highest. The priority of the WHO elimination campaign should be to increase both screening coverage and treatment of detected lesions; however, expanding the efforts of surveillance systems in both coverage and quality control are major challenges to achieving the WHO elimination target. Funding: Instituto de Salud Carlos III, European Regional Development Fund, Secretariat for Universities and Research of the Department of Business and Knowledge of the Government of Catalonia, and Horizon 2020.https://orcid.org/0000-0001-7187-9946Revista Internacional - IndexadaA1N

SP-0489: HPV-transformation in the cervix and at non-cervical sites

Pla general d'un dels panells horitzontals sobre espais verds de Barcelona a l'exposició Ciutat. Barcelona projecta a l'Edifici Fòrum. Exposició sobre la planificació urbanística i arquitectònica de Barcelon

Early age at first sexual intercourse and early pregnancy are risk factors for cervical cancer in developing countries

Early age at first sexual intercourse (AFSI) has long been associated with an increased risk of invasive cervical carcinoma (ICC). Age at first pregnancy (AFP) and ICC have been investigated less, although AFSI and AFP are strongly interrelated in most developing countries. A pooled analysis of case–control studies on ICC from eight developing countries with 1864 cases and 1719 controls investigated the roles of AFSI, AFP, and ICC risk. Age at first sexual intercourse, AFP and age at first marriage (AFM) were highly interrelated and had similar ICC risk estimates. Compared with women with AFSI ⩾21 years, the odds ratio (OR) of ICC was 1.80 (95% CI: 1.50–2.39) among women with AFSI 17–20 years and 2.31 (95% CI: 1.85–2.87) for AFSI ⩽16 years (P-trend <0.001). No statistical interaction was detected between AFSI and any established risk factors for ICC. The ICC risk was 2.4-fold among those who reported AFSI and AFP at ⩽16 years compared with those with AFSI and AFP at ⩾21 years. These data confirm AFSI and AFB as risk factors for ICC in eight developing countries, but any independent effects of these two events could not be distinguished