Normal Cytology Research Articles

Oral contraceptive and intrauterine device use and the risk of cervical intraepithelial neoplasia grade III or worse: a population-based study

ObjectiveHormonal contraceptive use has been associated with the development of cervical cancer, although inconsistent results are reported on the association with intrauterine device (IUD) use. The aim of this study was to evaluate the association between the type of contraceptive use and the development of cervical intraepithelial neoplasia grade III or worse (CIN3+). MethodsA retrospective population-based cohort study including women aged 29–44 years attending the cervical cancer screening program with normal cytology between 2005 and 2009 identified from the Dutch Pathology Registry. Subgroups with at least 5 years registered use of an oral contraceptive (OC) or IUD were compared with non-users. Risk ratios of CIN3+ were estimated per contraceptive type. Results702,037 women were included with a median follow-up of 9.7 years, of which 6705 (0.96%) and 559 (0.08%) women developed CIN3 and cervical cancer, respectively. IUD use was associated with an increased risk of developing CIN3+ (risk ratio (RR) 1.51, 95% confidence interval (CI) 1.32–1.74), and OC use was associated with an increased risk of developing CIN3+ (RR 2.77, 95%CI 2.65–3.00) and cervical cancer (RR 2.06, 95%CI 1.52–2.79). The risk of developing CIN3+ and cervical cancer was higher for OC users compared with IUD users (RR 1.83, 95%CI 1.60–2.09 and RR 1.70, 95%CI 1.00–2.90, respectively). ConclusionsBoth OC use and IUD use were associated with an increased risk of developing CIN3+. However, for women with a contraceptive wish, an IUD seems safer than an OC as the risk of developing CIN3+ and cervical cancer was higher for OC users.

Abstract DP-002: COMPARISON OF POTENTIAL OVARIAN CANCER BIOMARKERS BY MASS SPECTROMETRY-BASED PROTEOMIC ANALYSIS OF RESIDUAL PAP TEST FLUID, CERVICAL SWABS, AND TUMOR TISSUE FROM AN OVARIAN CANCER PATIENT

Abstract Early detection is the key to increased survival for women with ovarian cancer, yet a screening tool has yet to be developed that is adequately sensitive and specific enough for use in the general population. In contrast, screening for cervical cancer by Pap tests has been routinely performed for over 50 years. In the liquid-based Pap test, cells are collected from the cervix and placed into an alcohol-based fixative and then examined for abnormal cells. Since ovarian cancer cells have been observed in Pap tests, we reasoned that ovarian cancer peptide biomarkers may also be present. Our central hypothesis is that proteins shed by ovarian cancer cells can be detected during routine Pap tests by mass spectrometry (MS)-based proteomics. In particular, when collected at the time of cervical cancer Pap test screening, the alcohol-based Pap test fixative and cervical swabs are ideal for biomarker discovery since they are derived from a site near the ovarian cancer (i.e. proteins may be secreted or shed from the tumor and flow through the fallopian tube into the uterus and out the cervical opening). Recently, the fimbria of the fallopian tube have been suggested to be the true precursor to ovarian cancer, strengthening our hypothesis that ovarian cancer proteins will be found in the lower genital tract, perhaps even at early stages. To demonstrate the feasibility of using Pap tests as a biospecimen for proteomics, we previously examined the proteins present in residual Pap test fixative samples from women with normal cervical cytology by MS and described 152 proteins in the “Normal Pap Proteome.” The objective of this study was to identify and compare the proteins from three different sources from the same ovarian cancer patient: (i) the residual Pap test fixative, (ii) a Merocel swab of the cervix, and (iii) the primary ovarian cancer tumor tissue. Proteins were concentrated from the cell-free supernatant of the Pap test fixative or eluted from the swab, and then trypsin digested using the filter-aided sample preparation method. A total protein extract from the patient's tumor tissue was digested by standard in-solution trypsin digestion. The samples were run on 2D-liquid chromatography MS/MS, followed by bioinformatics integration. We identified over 5000 proteins total in the three samples. More than 2000 proteins were expressed in all three ovarian cancer samples, including several known ovarian cancer biomarkers such as CA125. By Scaffold analysis of the Gene Ontology nomenclature of the proteins, we classified the proteins by both cellular localization and biological processes. Additional matched samples from patients will be used to build a library of proteins and peptides that are specific to ovarian cancer for use in the development of targeted MS assays. We conclude that quantification of proteins from Pap test fixatives and cervical swabs will prove to be a rich source of biomarkers for ovarian cancer detection. Citation Format: Kristin L.M. Boylan, Anna C. Rogers, Melissa A. Geller, Peter A. Argenta, Timothy J. Griffin, and Amy P.N. Skubitz. COMPARISON OF POTENTIAL OVARIAN CANCER BIOMARKERS BY MASS SPECTROMETRY-BASED PROTEOMIC ANALYSIS OF RESIDUAL PAP TEST FLUID, CERVICAL SWABS, AND TUMOR TISSUE FROM AN OVARIAN CANCER PATIENT [abstract]. In: Proceedings of the 12th Biennial Ovarian Cancer Research Symposium; Sep 13-15, 2018; Seattle, WA. Philadelphia (PA): AACR; Clin Cancer Res 2019;25(22 Suppl):Abstract nr DP-002.

Lower genital tract infections in young female juvenile idiopathic arthritis patients

BackgroundTo evaluate human papillomavirus (HPV), Chlamydia trachomatis (CT) and Neisseria gonorrhoeae (NG) infections in juvenile idiopathic arthritis (JIA) patients.MethodsAfter exclusion, 33 female adolescent and young JIA patients (ILAR criteria) and 28 healthy controls were selected for this study. Demographic data, gynecological, sexual function, cervical cytology and histological abnormalities were evaluated. JIA clinical/laboratorial parameters and treatment were also assessed. HPV-DNA, CT-DNA and NG-DNA testing in cervical specimens were performed by Hybrid Capture 2 assays.ResultsThe mean current age was similar in JIA patients and controls (23.3 ± 6.24 vs. 26.1 ± 6.03 years, p = 0.09). The frequencies of sexual intercourse (76% vs. 89%, p = 0.201) and abnormal cervical cytology (24% vs. 11%, p = 0.201) were similar in JIA compared to controls. The higher frequency of HPV infection in JIA patients than controls (30% vs. 11%, p = 0.155) did not reach statistical significance. CT (0% vs. 7%, p = 0.207) and NG infections (0% vs. 4%, p = 0.459) were also alike in both groups. Further evaluation of JIA patients with abnormal and normal cervical cytology showed that the former group had a higher frequency of HPV infection (87% vs. 12%, p = 0.0002) with a low frequency of HPV vaccination (0% vs. 8%, p = 1.0). No differences were evidenced between these two JIA groups regarding demographic data, sexual function and clinical/laboratorial parameters. The frequencies of methotrexate (p = 0.206) and biological agent use (p = 0.238) were similar in both JIA groups.ConclusionsTo our knowledge, this was the first study to assess lower genital infections in JIA patients allowing the identification of HPV as main cause of cervical dysplasia. Methotrexate and biological agents do not seem to increase risk of lower genital tract infections in JIA patients.

Triaging women withhuman papillomavirus infection andnormal cytology or low-grade dyskaryosis: evidence from 10-year follow up of the ARTISTIC trial cohort.

ObjectivesTo estimate long‐term cervical intraepithelial neoplasia grade 3 (CIN3) risks associated with different triage strategies for human papillomavirus positive (HPV+) women with a view to reducing unnecessary referrals.DesignThe ARTISTIC trial cohort was recruited in Manchester in 2001–03 and was followed up for CIN3 and cancer notification through national registration until December 2015.ResultsThe 10‐year cumulative risk of CIN3+ was much higher for women with HPV16/18 infection (19.4%, 95% CI 15.8–23.8% with borderline/low‐grade cytology and 10.7%, 95% CI 8.3–13.9% with normal cytology) than for those with other HPV types (7.3%, 95% CI 5.4–9.7% with borderline/low‐grade cytology and 3.2%, 95% CI 2.2–4.5% with normal cytology). Among the 379 women with normal to low‐grade cytology and new HPV infection, the 10‐year cumulative CIN3+ risk was 2.9% (95% CI 1.6–5.2%).ConclusionsThe CIN3 risk is confined to women with persistent type‐specific HPV so partial genotyping test assays identifying HPV16/18 as a minimum are essential for efficient risk stratification. Immediate referral to colposcopy for HPV+ women with borderline or low‐grade cytology and referral after a year if still HPV+ with normal cytology may be unnecessary. Low‐grade lesions can safely be retested to identify those with persistent HPV. Recall intervals of 1 year for HPV16/18 and 2 years for other high‐risk HPVs are justified for women with normal cytology and might also be considered for women with borderline/low‐grade cytology. The minimal risk of invasive cancer that has progressed beyond stage 1A must be weighed against the advantages for patients and the NHS of reducing the number of referrals to colposcopy.Tweetable abstractCervical screening would be better for women and cheaper for the NHS if women with HPV and normal to low‐grade cytology were retested after a year or two when many infections will have cleared.

Molecular detection of HPV and FT-IR spectroscopy analysis in women with normal cervical cytology.

The increase in the incidence of Cervical Cancer in the female population worldwide has been an issue that deserves further attention from the scientific community. Several studies have already proven the relationship of its development with the molecular mechanisms that Human Papillomavirus (HPV) induces in cervical cells. The gene amplification provided by molecular biology techniques has been used as the gold standard diagnostic method of this virus because of its high specificity and sensitivity.However, the high investments associated with the acquisition of reagents, equipment and labor demonstrate the need for the development of more accessible techniques that present the same accuracy. FT-IR spectroscopy has been studied as an inexpensive and easily accessible technology that can provide the differentiation of malignant and benign cells. This study aimed to demonstrate the effectiveness and sensitivity of molecular analysis by PCR in relation to cytological analysis and to evaluate the sensitivity of FT-IR spectroscopy in the diagnosis of HPV for cervical cancer prevention. Cervical fluid samples obtained from 50 patients with absence of cellular lesion by cytological analysis were analyzed by molecular and spectroscopic analyzes. Oncotic colpocitology analysis was performed by the Papanicolaou staining, amplification of the L1 viral gene by PCR was performed using primers MY09 and MY11 and biochemical analysis of the fluids by FT-IR was performed using the Spectrum 400 system equipped with a microscope. Of the 50 patients without evident morphological alteration of the cells, seven were diagnosed by molecular analysis as positive for presence of HPV. Principal component analysis of spectroscopy was not able to separate the negative samples from the HPV positive samples and, therefore, did not present as an effective diagnostic technique. We highlight the efficacy, sensitivity and specificity of molecular biology by PCR in the identification of the virus and we emphasize that more studies should be used for the application of FT-IR spectroscopy in the diagnosis of this infection and its application in the prevention of cervical cancer.

Quality control of cervical cytology using a 3-type HPV mRNA test increases screening program sensitivity of cervical intraepithelial neoplasia grade 2+ in young Norwegian women-A cohort study.

Within 2021, Norway intends to complete implementation of HPV DNA-based primary screening for cervical cancer for women 34–69 years, while continue cytology-based screening for women 25–33 years. Over the recent years, the incidence of cervical cancer has increased by 30% among women younger than 40 years. In this subset of women, nearly 30% were diagnosed with a normal smear, as most recent smear, prior the cancer diagnosis. This observation demands quality control of normal smears. The aim of this study was to assess increase in program sensitivity of CIN2+ after follow-up of women with false negative Pap-smears testing positive for a 3-type (-16, -18, -45) HPV mRNA test in a cohort design over one screening interval. 521 women, aged 23–39 years, and no prior history of CIN1+ or HSIL, with an ASC-US or worse smear (ASC-US+) and 1444 women with normal screening cytology comprised the study cohorts. The positivity rate for the 3-type HPV mRNA was 1.9% (28/1444). Rescreening revealed 23 women with ASC-US, two women with LSIL, two women with ASC-H, and one woman with AGUS. If the HPV mRNA-positivity rate and histology findings from samples rescreened were applied to all women with normal cytology, an estimated increase in screening sensitivity of 16.4% (95% CI:15.3–17.5) for CIN2+ and 17.3% (95% CI:16.2–18.4) for CIN3+ were achieved. By rescreening less than 2% of women with normal cytology positive for a 3-type HPV mRNA test, we achieved a significant increase in screening program sensitivity.

Natural History of Anal Squamous Intraepithelial Lesions in HIV-Positive Men with Normal Baseline Cytology.

The natural history of squamous intraepithelial lesions (SILs) in the anal canal of HIV-infected men is incompletely understood. We assessed the incidence and factors associated with SIL and invasive anal squamous cell carcinoma (IASCC) among HIV-infected men with normal cytology at baseline. We performed a single-center prospective cohort study [men who have sex with men (MSM) and men who have sex with women (MSW)]. The incidence of anal canal SIL (low grade and high grade) and IASCC were estimated and predictive factors analyzed. The study population comprised 297 HIV-infected men with a normal cytology result and no anal human papillomavirus (HPV)-related diseases. Of these, 251 (85%) had at least one evaluable set of cytology data during follow-up (172 MSM, 79 MSW). The median follow-up time was 4 years. The cumulative incidence of SIL was 43% (107/251): 52% in MSM (90/172) and 22% in MSW (17/79), p < 0.0001. The incidence rate of SILs was 109 (95% confidence interval = 90-132) per 1000 person-years: 142 in MSM and 49 in MSW, p < 0.0001. HPV infection, receiving antiretroviral treatment (ART), and being MSM were independently associated risk factors. The incidence of IASCC was 0.15 per 1000 person-years among MSM and 0 in MSW. HIV-infected men, both MSM and MSW, are at high risk of developing SIL despite having a normal anal cytology at baseline. The incidence of anal canal SIL was higher among MSM, but was also remarkable among MSW. Independent risk factors associated with SIL were being HIV-infected MSM at high risk for acquisition of STIs, time on ART, and HPV infection.

Systematic Review and Meta-Analysis of Human Papillomavirus Prevalence and Types Among Women With Normal Cervical Cytology in the Eastern Mediterranean Region

Aim: To predict the impact of human papillomavirus (HPV) vaccines in the Eastern Mediterranean Region (EMRO), knowing the prevalence and type distribution of HPV are mandatory. Methods: This study investigated 26,536 women with normal cervical cytology based on the data available from 13 countries of EMRO. Results: The HPV prevalence estimated to be 9.3% (CI = 7.1–12.0). The five most frequent HPV types were HPV 16 (2.3%), 18 (0.7%), 6 (0.7%), 11 (0.6%) and 31 (0.5%). The prevalence of multiple infections of HPV was observed in 1.6% of all cases. Conclusion: The present meta-analysis provides a comprehensive summary of HPV type distribution in normal cervical cytology in EMRO region to estimate and predict the impact of HPV vaccines.

Presence of Glandular Cells at the Preoperative Cervical Cytology and Local Recurrence in Endometrial Cancer.

We investigated the correlation between glandular cells (GC) detected at preoperative cervical-smear and the histologic findings and oncologic outcomes in patients undergoing surgery for endometrial cancer (EC). We retrospectively analyzed data of all consecutive EC patients who underwent surgery between January 1, 1990 and December 31, 2012 with preoperative cervical smear performed within 3 mo from the EC diagnosis. Basic descriptive, logistic regression and artificial neural network analyses were used. Five-year disease-free survival and overall survival were assessed using Kaplan-Meier and Cox hazard models. The study included 229 (89%) and 29 (11%) patients with normal cytology (control group) and GC (GC group), respectively. A higher proportion of elderly patients with nonendometrioid and FIGO grade 3 EC was observed in the GC group compared with the control group (P<0.05). No differences in 5-yr disease-free survival and overall survival were observed. However, patients in the GC group experienced a higher local recurrence rate (hazard ratio: 7.6; 95% confidence interval: 1.7-34.2; P=0.008). We observed that age, body mass index, cervical stromal invasion, vaginal brachytherapy, and GC influenced the risk for developing local recurrence. However, at the multivariable analysis, only cervical stromal invasion (odds ratio: 1.2; 95% confidence interval: 1.02-1.4; P=0.02) and GC (odds ratio: 1.07; 95% confidence interval: 1.01-1.14; P=0.03) correlated with the increased risk. In addition, the results of an artificial neural network analysis reported that the most critical predictor of local failure was cervical stromal invasion (importance: 0.352) followed by GC (importance: 0.194). These results suggest that cervical stromal invasion and presence of GC at the preoperative cervical smear might predict the occurrence of local recurrence in EC.

Viral load of human papillomavirus types 16/18/31/33/45 as a predictor of cervical intraepithelial neoplasia and cancer by age

ObjectiveWe assessed whether human papillomavirus (HPV) viral load is an independent predictor of underlying cervical disease and its diagnostic accuracy by age. MethodsThe Biomarkers of Cervical Cancer Risk study was a case-control study from 2001 to 2010 in Montréal, Canada. Cases were histologically-confirmed cervical intraepithelial neoplasia (CIN), adenocarcinoma in situ (AIS), or cervical cancer cases. Controls were women presenting for routine screening with normal cytology results. We quantified HPV16/18/31/33/45 viral load from exfoliated cervical cells using a real-time PCR assay. Diagnostic accuracy of viral load was assessed using the area under the receiver operating characteristic curve (AUC). We restricted the analysis to the 632 cases and controls who were HPV16/18/31/33/45 positive. ResultsGeometric mean HPV16/18/31/33/45 viral load increased with severity of lesion grade, ranging from 0.7, 3.1, 4.8, 7.2, and 12.4 copies/cell in normal, CIN1, CIN2, CIN3&AIS, and cervical cancer respectively. The adjusted odds ratio of CIN1+ and CIN2+ increased respectively by 1.3 (95%CI 1.1–1.4) and 1.2 (95%CI 1.1–1.3) per log-transformed viral copy/cell increase of HPV16/18/31/33/45. This association was mainly driven by HPV16, 18, and 31 viral loads. The AUC of HPV16/18/31/33/45 viral load for discriminating between normal and CIN1+ women was 0.70 (95%CI 0.64–0.76) in HPV-positive women, and was 0.76 (95%CI 0.66–0.86) for women ≥30 years and 0.66 (95%CI 0.58–0.74) for women under 30 years. ConclusionsHPV viral load has lower diagnostic accuracy than has been reported for other HPV screening triage tests. However, it may be useful for triaging HPV tests in settings without cytology results such as HPV self-sampling.

Mutational landscape and intra-host diversity of human papillomavirus type 16 long control region and E6 variants in cervical samples.

Human papillomavirus genotype 16 (HPV16) is the most frequent high-risk HPV (HR-HPV) identified in cervical precursor lesions and cervical cancer (CC) worldwide. The oncogenic potential of HPV16 is partly dependent on the lineage involved in the infection and the presence of clinically relevant mutations. In this report, we present the distribution of HR-HPV and the mutational profile and intra-host variability of HPV16 lineages, based on analysis of the long control region (LCR) and the E6 gene in samples with normal cytology (n = 39), squamous intraepithelial lesions (n = 25), and CC (n = 39). HR-HPV genotyping was performed using multiplex real-time PCR. HPV16 lineage assignments and mutation frequencies were determined by conventional PCR and Sanger DNA sequencing, and intra-patient viral populations were analyzed using next-generation sequencing (NGS). The most frequent HR-HPV type was HPV16, followed by HPV31 and HPV18. The frequency of HPV16 sublineages was A1/A2 > D2 > D3 and B1. Moreover, the most frequent mutations, both in samples from this study and in the available sequences from Mexican isolates in the GenBank database were LCR-G7518A, which is involved in carcinogenesis, and E6-T350G (producing L83V), associated with persistence of infection. Otherwise, deep sequencing revealed high conservation of viral lineages and mutations, independently of the stages studied. In conclusion, the high frequency and stability of these molecular markers, as well as the circulating viral lineages, could be related to the incidence of CC associated with HPV16. Hence, they deserve a broader analysis to determine the risk of specific populations for progression of the disease.

HPV infection screening using surface plasmon resonance in women from Kunming (Southwest China).

No study examined the frequency of human papillomavirus (HPV) genotypes by surface plasmon resonance (SPR) in Southwest China. This was a cross-sectional survey (The Second Affiliated Hospital of Kunming Medical University, 10/2010 to 12/2011) in 150 patients who were hospitalized or volunteered for cervical cancer (CC) screening. A HPV typing kit was used to detect 24 types of HPV by the SPR technique. The HPV-positive rate was 34.8% in women with normal cytology and 92.9% in women with CC. The frequency of HPV16 increased from 9.4% for women with normal cytology to 28.9% for cervical intraepithelial neoplasia (CIN)1, 41.4% for CIN2, 54.1% for CIN3, and 71.4% for CC (p < 0.001). The frequency of HPV18 increased from 0% for women with normal cytology to 2.6% for CIN1, 3.4% for CIN2, 5.4% for CIN3, and 21.4% for CC (p = 0.03). HPV40 was only found in one patient with CC (p = 0.04). There was no relation between HPV genotype and women’s age. In Kunming (Southwest China), the frequency of HPV infection was 74.0% among women who underwent CC screening. HPV16 and HPV18 were the two most frequent genotypes. SPR could be of value for the screening of HPV infection.

Isolated Non-16/18 High-Risk Human Papillomavirus Cervical Infection: Re-Evaluation After One Year.

High-risk human papillomavirus cervical infection is currently a well-established cause of cervical cancer. However,only a few women with persistent infections will develop cervical precancerous and malignant lesions. Approximately 20% of all cervical cancers are attributable to non-16/18 serotypes. This study aims to evaluate the results of our clinical approach to women withthis infection. We conducted an observational and prospective study from September 2012 to September 2017, which included women with isolated non-16/18 high-risk human papillomavirus infection (with normal cytology). After re-evaluation, two groupswere compared: women with spontaneous regression of the infection and women with persistent infection. Clinical and demographicdata were analysed as well as the rate of progression to precancerous and malignant lesions. We included 165 women, of which 121 were re-evaluated with co-test at least one year later. After re-evaluation, 13.2% ofwomen revealed precancerous lesions but only two (1.7%) of them presented high-grade squamous intraepithelial lesions. Sixty-sevenwomen (55.4%) showed spontaneous regression of the infection and 54 women (44.6%) maintained it. Women with persistent infectiondeveloped more precancerous lesions (27.8%; p < 0.001) and high-grade squamous intraepithelial lesions (3.7%; p < 0.001). Therewas also an association between persistent infection and postmenopausal status. Human papillomavirus 16/18 cervical infection is associated with higher risk of cervical cancer when compared with other serotypes. Re-evaluation with co-test one year after the diagnosis of isolated non-16/18 human papillomavirus infection seems tobe a reasonable approach.

Is the risk of cervical atypia associated with the interval between menarche and the start of sexual activity? A population-based cohort study

ObjectiveWe investigated whether the risk of cervical atypia is associated with a short interval between the age at first sexual intercourse (FSI) or age at the start of oral contraceptive...

Neutrophil-to-Lymphocyte Ratio and Platelet-to-Lymphocyte Ratio in Discriminating Precancerous Pathologies from Cervical Cancer

Purpose We aimed to determine the predictive value of several hematological markers of inflammation on the presence/absence of cervical cancer and also to determine their ability in discriminating precancerous cervical pathologies from cervical cancer. Materials and Methods In this study, patients who presented to Acıbadem Kayseri Hospital between May 2010 and June 2018 were evaluated. Forty patients with low-grade squamous intraepithelial lesions (LSIL), 40 patients with high-grade squamous intraepithelial lesions (HSIL), and 30 patients with cervical cancer (CC) were retrospectively included in this study. A control group of 70 healthy volunteers with normal cervical cytology was also included in the study. Results The neutrophil-to-lymphocyte ratio (NLR) was significantly higher in patients with CC than in controls. The platelet-to-lymphocyte ratio (PLR) was significantly higher in patients with CC compared to those with LSIL and HSIL diagnoses and also controls (p < 0.001). Logistic regression analysis revealed that age (OR: 1.075, 95% CI: 1.020–1.132, p=0.007), NLR (OR: 1.643, 95% CI: 1.009–3.142, p=0.047), and PLR (OR: 1.032, 95% CI: 1.003–1.062, p=0.029) were predictors for the presence of CC. ROC curve analysis revealed that both NLR and PLR were predictive of CC with a cutoff value of 2.02 for NLR (71% sensitivity and 60% specificity, AUC: 0.682, p=0.004) and 126.7 for PLR (83% sensitivity and 69% specificity, AUC: 0.752, p < 0.001). Conclusion In addition to patients' age, determination of NLR and PLR values, which are simple, inexpensive, and readily available markers of systemic inflammation, may help in decision making precancerous pathologies of the cervix.

Ovarian stimulation does not influence the uterine immune environment in healthy infertile women.

There is some controversy regarding the impact of ovarian stimulation on immune cells in women undergoing IVF. The study's aim was to determine whether ovarian stimulation affected immune uterine cells in healthy women undergoing IVF. This prospective cohort study included 28 patients undergoing IVF and 47 healthy oocyte donors. Endometrial biopsies were taken in a natural cycle and after ovarian stimulation. All participants had a normal karyotype, pelvic ultrasound and cervical cytology results and thyroid-stimulating hormone concentration, as well as normal glucose and insulin concentrations and inherited and acquired thrombophilia test results. Screening tests including human papillomavirus were normal. Immune cells were analysed using three techniques: fluorescence-activated cell sorting, immunohistochemistry and gene expression. A human leukocyte antigen (HLA)-C tetramer was used as an 'artificial embryo'. The expression of genes including those for tumour necrosis factor (TNF)-α and interleukin-10 (IL-10) was analysed. A comparison was made of the percentage and gene expression of CD56brightCD16- uterine natural killer (uNK), CD56dimCD16+ natural killer cells, CD56-CD16+ natural killer cells and TregCD25+CD4+FoxP3+ cells, uNK binding to the HLA-C tetramer, and TNF-α and IL-10 expression. No between- or within-group differences were observed in natural versus ovarian stimulation cycles. Ovarian stimulation does not affect the uterine immune cell population or HLA-C binding in healthy women undergoing ovarian stimulation. Further studies are underway to find out if different responses might be seen in women with previous autoimmune disorders.

Cervical high-risk human papillomavirus infection among women residing in the Gulf Cooperation Council countries: Prevalence, type-specific distribution, and correlation with cervical cytology.

The scarcity of updated data on the prevalence of cervical human papillomavirus (HPV) infection in the Gulf Cooperation Council (GCC) countries hampers the establishment of cervical cancer screening and HPV vaccination programs. The current study estimated the prevalence of cervical high-risk (HR) HPV infection among women residing in some countries of the GCC and analyzed the correlation between HR-HPV infection types and cytology results. In total, 2478 women residing in the Kingdom of Saudi Arabia, Qatar, the United Arab Emirates, and Bahrain were enrolled in this study. Cervical specimens were subjected to simultaneous liquid-based cytology and HR-HPV DNA analysis. Of 2478 women, 520 (21%) tested positive for HR-HPV. Other non-HPV genotype 16 (HPV16)/HPV18 HR-HPV was the most frequently detected infection type, accounting for 63.7%. Non-Arab women had a significantly higher HR-HPV positivity rate compared with Arab women (31.6% vs 16.4%; P<.001). The HR-HPV positivity rate was highest among women residing in Qatar (31.3%), followed by women living in Bahrain (20%), the Kingdom of Saudi Arabia (17.2%), and the United Arab Emirates (14.7%). The overall prevalence of HR-HPV infections declined significantly with advancing age (P<.001). Women with abnormal cytology had a significantly higher HR-HPV positivity rate than those with normal cytology (50.6% vs 14.7%; P<.001). The HR-HPV positivity rate increased as the severity of the cytological lesion increased. The current study provides updated data on HR-HPV prevalence in the GCC countries and delivers an evidence base for supporting the introduction of regional/national vaccination and screening programs in these countries.

High-Risk HPV Testing in Primary Screening for Cervical Cancer in the Public Health System, São Paulo, Brazil

Every year there are approximately 16,000 new cases of cervical cancer in Brazil. Novel screening technologies may reduce this number by expanding the population coverage but also by improving the detection rate of precursor lesions. We aimed to evaluate human papillomaviruses (HPV)-DNA testing in the context of routine cervical cancer screening in the public health system of the city of São Paulo, Brazil. Women participating in the primary screening program were invited to enroll. Liquid-based cytology samples were collected and cytology and Hr-HPV DNA testing were performed in parallel. Cytologists were blind to HPV results. Women older than 24 years with a positive high-risk HPV test and/or cytology class ≥ ASC-US were referred to colposcopy. From December 2014 to December 2016, 16,102 women joined the study. High-risk human papillomavirus (HR HPV) DNA prevalence was 14.9%, whereas cytologic abnormalities were found in 7.2% of the women. Per protocol, 1,592 Hr-HPV+ women, in addition to 72 patients with cytologic classification > low-grade squamous intraepithelial lesion (LSIL) were referred. A total of 80 cervical intraepithelial neoplasia (CIN2+) cases were diagnosed, 79 were Hr-HPV DNA+ and 18 had normal cytology. Hr-HPV DNA detected a significant number of patients with premalignant lesions missed by cytology and all 16 CIN3+ cases were Hr-HPV DNA+ HPV genotyping may be useful in the management of Hr-HPV+ women, reducing the burden of colposcopic referral for those harboring genotypes with a weaker association to CIN3+ Use of HPV-DNA testing was shown to be feasible and advantageous over current cytologic screening in the public health system.

Anxiety and distress following receipt of results from routine HPV primary testing in cervical screening: The psychological impact of primary screening (PIPS) study.

We used a cross‐sectional survey to examine short‐term anxiety and distress in women receiving different results following routine human papillomavirus (HPV) primary testing at cervical screening. Participants were women aged 24–65 (n = 1,127) who had attended screening at one of five sites piloting HPV primary screening in England, including a control group with normal cytology who were not tested for HPV. Women completed a postal questionnaire ~2 weeks after receiving their screening result. Unadjusted mean anxiety scores ranged from 32.9 (standard deviation [SD] = 12.2) in HPV‐negative women to 42.1 (SD = 14.9) in women who were HPV‐positive with abnormal cytology. In adjusted analyses, anxiety was significantly higher in women testing HPV‐positive with either normal cytology (mean difference [MD] = 3.5, CI: 0.6–6.4) or abnormal cytology (MD = 7.2, CI: 3.7–10.6), than the control group. Distress was slightly higher in women who tested HPV‐positive with abnormal cytology (MD = 0.9, CI: 0.02–1.8), than the control group. We also found increased odds of very high anxiety in women who tested HPV‐positive with normal or abnormal cytology compared to the control group. This pattern of results was only observed among women receiving their first HPV‐positive result, not among women found to have persistent HPV at 12‐month follow‐up. Testing HPV‐positive with normal cytology for the first time, is associated with elevated anxiety despite carrying very low immediate cervical cancer risk. However, receiving the same test result at 12‐month early recall does not appear to be associated with higher anxiety, suggesting anxiety may normalise with repeated exposure and/or over time.

Detection of human herpesvirus 6 (HHV-6) and human herpesvirus 7 (HHV-7) DNA in endocervical samples from a positive and negative HPV woman of Córdoba, Argentina

AimsThe purpose of the present study was to elucidate the presence of human herpesvirus 6A (HHV-6A), HHV-6B and HHV-7 in samples of the uterine cervix through detection of viral DNA....