Evaluation of Endocervical Curettage in Colposcopy in the Turkish Cervical Cancer Screening Program.

Background/Objectives: To investigate the risk factors for CIN2+ lesions (cervical intraepithelial neoplasia 3 or worse) in endocervical curettage (ECC) and to evaluate the relationship between the addition of ECC to punch biopsy in terms of the yield of CIN2+ lesions. Methods: Between February 2018 and 2019, data on colposcopy results from 11,944 patients were gathered from the Cancer Department of the Turkish Ministry of Health across the country. A total of 6370 women whom were referred to colposcopy were included in this study. Risk factors were identified using both univariate and multivariate logistic analyses. Results: The median age was 42 years old (range, 30-65). ASC-H (atypical squamous cells-suggestive of high-grade squamous intraepithelial lesion)/HSIL (high-grade intraepithelial lesion) cytology (OR 7.648 95% CI (3.933-14.871)) and HPV (human papillomavirus)-16/18 infection (OR 2.541 95% CI (1.788-3.611)) were identified as risk factors for having CIN2+ lesions. CIN2+ diagnostic yield by ECC is only 1.2% all patients. CIN2+ diagnostic yield by punch biopsy and ECC are 9.7% and 6% of patients, respectively. A higher CIN2+ yield by ECC was observed with increasing age. Among cytology groups, ASC-H/HSIL has highest CIN2+ yield by ECC. Finally, in patients with incomplete visualization of the squamocolumnar junction (SCJ), ECC yields approximately twice as many CIN2+ lesions. Conclusions: ECC should be considered in cases of advanced patient age and in situations where the SCJ is not routinely visualized. In addition, evaluation of the endocervical canal is necessary in HPV-positive cases infected with HPV-16/18 types and in cases infected with HPV of any type but with cytological abnormalities.

Evaluation of colposcopy after the addition of human papillomavirus testing to the Turkish cervical cancer screening program.

OBJECTIVE: To evaluate colposcopy performance following the human papillomavirus (HPV) DNA screening program in Turkey. METHODS: Women aged 30-65 years are screened for cervical cancer every 5 years, with individuals positive for HPV 16 and/or 18 or other high-risk HPV types with abnormal cytology referred for colposcopy. Both HPV test and cytology are obtained at the same visit. If HPV is negative, cytology will not be assessed. However, if HPV is positive, both cytology and HPV genotyping will be performed. Colposcopy-require was defined as HPV 16/18 positivity or abnormal smear results with any hrHPV positivity, and the remaining patients (normal smear with hrHPV positivity other than HPV 16/18) were grouped as colposcopy non-required. National data on colposcopy outcomes and unnecessary performance rates in February 2018-2019 were evaluated via a questionnaire. RESULTS: A total of 9808 patients were included, divided based on colposcopy requirement: 5751 (58.6%) patients required colposcopy and 4057 (41.4%) did not. Unnecessary colposcopy was performed on 90.1% of the non-required group (3657 of 4057 patients). In the colposcopy-required group, 4455 patients (79.9%) underwent punch biopsy; 3194 (57.1%), endocervical curettage (ECC); and 421 (7.5%), "see and treat" in the non-required group, the results were 2790 (76.3%), 1957 (53.2%), and 211 (5.7%), respectively. A total of 746 cervical intraepithelial neoplasia (CIN)-3 isolates were detected, including 702 using existing screening and triage with 94.1% sensitivity (702/746). Multiple biopsies were taken in 69.8% (n = 3110) of patients from the colposcopy-required group and 63.7% (n = 1777) from the non-required group. The ECC samples included 19 cervical cancers and 212 ≥CIN-3 lesions in the colposcopy-required group, and four cancers and 41 ≥CIN-3 lesions in the non-required group. The proportion of ≥CIN-3 lesions detected by ECC only was 4.7% (35 of 746 ≥CIN-3 lesions). CONCLUSION: Our results showed high rates of unnecessary colposcopies, and a high percentage of multiple and random punch biopsies and ECC.

Endocervical polyps in high risk human papillomavirus infections.

OBJECTIVES: Human papillomavirus (HPV) positive patients with and without endocervical polyps is compared with respect to HPV genotypes and presence of pre-invasive diseases. To our knowledge, this is the first and largest report in the literature examining the endocervical polyps in HPV positive cases. MATERIAL AND METHODS: Clinicopathological data for the first one million screening patients (n = 1060 992) from around the entire country during 2015 and 2016 were targeted for this research. Colposcopy, colposcopic surgical diagnostic procedures and final pathology results of 3499 patients with high-risk (HR) HPV-positive were obtained from reference colposcopy centers. Patients with endocervical polyps (n = 243 [6.9 %]) were accepted as experimental arm while patients without any endocervical polyp (n = 3256 [93.1%]) were regarded as the control group. Age, HPV genotype, Pap smear abnormality, and final pathological results were compared between two groups using Student's t-test and cross-tabulation chi-square test. RESULTS: The incidence of endocervical polyp was found to be 6.9 % in HR HPV-positive women. The most common HPV genotypes observed in both groups were HPV 16 or 18. Abnormal cytology reports (≥ ASC-US) were not significantly different between both groups. However, with respect to final pathological diagnosis, patients with endocervical polyp had significantly lower numbers of pre-invasive diseases (31.3% vs 44.2%; p < 0.10). CONCLUSIONS: Endocervical polyps may be more common in patients with HR HPV infections. HPV 18 is observed significantly more, in the HR HPV positive endocervical polyp group. Patients with endocervical polyps do not have increased risk for preinvasive cervical diseases.

How to triage HPV positive cases: Results of four million females.

OBJECTIVE: To evaluate the Turkey's nationwide HPV DNA screening program on the basis of first 4 million screened women. METHODS: Women over age 30 were invited for screening via HPV DNA and conventional cytology. Single visit screen strategy was used to collect for both screening and triage (extended genotyping and conventional pap-smear). RESULTS: A total of 4,099,230 patients had attended to HPV DNA cancer screening. 4.39% were found to be HPV DNA positive. The most common HPV type was 16, followed by 51, 31, 52, 56 and 18 at all age intervals and geographic regions. Cytology results were reported as "normal" in (69.2%), "inadequate sampling" in (16.6%) and as "abnormal (≥ASC-US)" in the remaining. Current Turkish screening with HPV DNA (referral to colposcopy with HPV 16 or 18 or any smear abnormality ≥ASC-US) gives overall PPV of 24.3% for ≥CIN2. Only Pap-Smear triage revealed PPV of 26.4% for ≥ASC-US thresholds. Comparison of different triage methods for ≥CIN2+ according to different HPV genotype revealed a PPV of 32,6% for HPV 16; 15,3% for HPV 18. This figure was 34.4%, 19.3%, 15.3% and 14.0% for HPV 33, 31, 45 and 35; respectively. CONCLUSION: This study involves the largest series in the world summarizing a real-world experience with primary HPV DNA screening and triage with a single visit. The results show the feasibility and applicability of such screening method in developing countries with acceptable colposcopy referral rates. Among triage tests, only pap-smear seems to be effective without a need for extended genotyping.

Mega Hpv laboratories for cervical cancer control: Challenges and recommendations from a case study of Turkey.

Cervical cancer is the fourth most common cancer among women in the world. It is estimated that one woman dies every 2 min from cervical cancer. Nearly all cervical cancers are preventable by early detection and treatment through screening or HPV vaccination. In 2018, World Health Organization (WHO) made a global call for action toward the elimination of cervical cancer. Cervical cancer screening involves a complex organized program, which begins with a call/recall system based on personal invitation of eligible women, followed by participation in screening, and leading to diagnosis, treatment, and management as appropriate. An effective cervical screening program with high coverage is dependent on each country's infrastructure and human resource capacity. Efforts to develop an effective program is particularly challenging in low and middle income countries (LMIC) where resources are limited. For an effective strategy, Turkey redesigned the country's cervical screening program. The local call/recall system and centralized monitoring system of individual women were re-vamped with an automated evaluation system. The revised screening program includes the use of primary HPV testing with a well-defined protocol outlining the algorithms of management (i.e., screening intervals and referral), a single nationwide centralized diagnostic laboratory, and a sustainable agreement with the HPV diagnostics industry. This system allows for traceable, real-time monitoring of screening visits and specimens. Turkey reports on the first four years of this re-vamped organized program and shares lessons learnt from the implementation of this new program.

Synthesis, Structural Analysis, and Biological Activities of Some Imidazolium Salts.

Four newly synthesized imidazolium salts were characterized by nuclear magnetic resonance, vibrational spectra, and mass spectra. Then, the density functional theory calculations were performed to obtain the molecular configurations on which the theoretical nuclear magnetic resonance and infrared spectra were consequently obtained. The comparison of calculated spectra with the experimental spectra for each molecule leads to the conclusion that the theoretical results can be assumed to be a good approach to their molecular configurations. The in vitro biological activities of the salts on the selected bacteria and cancer cell lines were determined by using the broth dilution method according to Clinical and Laboratory Standards Institute guidelines. The 1,3-bis(2-hydroxyethyl) imidazolidinium bromide and 3-(2-ethoxy-2-oxoethly)-1-(3-aminopropyl)-1H-imidazol-3-ium bromide showed efficiency on Bacillus cereus ATCC 11778. The 3-bis(2-carboxyethyl)-4-methyl-1-H-imidazol-3-ium bromide was effective on HeLa while a similar effect was observed on Hep G2 with 3-(2-carboxyethyl)-1-(3-aminopropyl)-1H-imidazol-3-ium bromide.

Complexation, thermal and catalytic studies of N-substituted piperazine, morpholine and thiomorpholine with some metal ions.

Several Cu(II), Pt(II) and Ni(II) complexes of N-substituted, piperazine (NN donor), morpholine (NO donor) and thiomorpholine (NS donor) derivatives were synthesized and their thermal behavior and catalytic activity in epoxidation reaction of cis-diphenylethylene were studied using oxygen sources NaOCl. The coordination compounds of Cu(II), Pt(II) and Ni(II) having general formula [MLCl]Cl, [ML2l]Cl2 or [ML]Cl2 with tetra coordinated geometry around metal ions have been isolated as solid. All the ligands and complexes were identified by spectroscopic methods and elemental analysis, magnetic measurements, electrical conductance and thermal analysis. A square planer structures have been proposed for all complexes. The thermal stability of the complexes discussed in terms of ligands donor atoms, geometry and central metal ions. The complexes have a similar thermal behavior for the selected metal ions. The thermogravimetric analyses suggest high thermal stability for most complexes followed by thermal decomposition in different steps. The decomposition processes were observed as water elimination, chloride anion removal and degradation of the organic ligands. Catalytic ability of the complexes were examined and found that all the complexes can effectively catalyze the epoxidation of cis-stilbene with NaOCl.

1,1'-(Piperazine-1,4-di-yl)dipropan-2-ol.

The asymmetric unit of the crystal contains one-fourth of the title compound, C(10)H(22)N(2)O(2), with the centre of the piperazine ring located at a site of 2/m symmetry. The piperazine ring adopts a chair conformation. The methine and methylene C atoms of the 2-hydroxypropyl groups show symmetry-imposed disorder over two equally occupied and mutually exclusive sets of positions. Only intra-molecular O-H⋯N contacts are observed.

Synthesis, spectroscopic characterization, X-ray structure and DFT studies on 4-(2-hydroxyphenyl)-4,5,6,7-tetrahydro-1H-imidazo[4,5-c]pyridin-5-ium chloride hydrate.

The title molecular salt, 4-(2-hydroxyphenyl)-4,5,6,7-tetrahydro-1H-imidazo[4,5-c]pyridin-5-ium chloride hydrate (C(12)H(14)N(3)O(+)·Cl-·H(2)O), was synthesized and characterized by IR-NMR spectroscopy and single-crystal X-ray diffraction. In addition to the molecular geometry from X-ray experiment, the molecular geometry, vibrational frequencies and gauge-independent atomic orbital (GIAO) (1)H and (13)C NMR chemical shift values of the title compound in the ground state have been calculated using the density functional theory (DFT/B3LYP) method with the 6-31++G(d,p) and 6-311++G(d,p) basis sets, and compared with the experimental data. Besides, molecular electrostatic potential (MEP) distribution and non-linear optical properties of the title compound were investigated by theoretical calculations at the B3LYP/6-311++G(d,p) level.

2-[2-(1H-Imidazol-3-ium-5-yl)eth-yl]-3-(pyridin-2-yl)-2H-imidazo[1,5-a]pyridin-4-ium bis-(perchlorate).

In the title mol-ecular salt, C(17)H(17)N(5) (+)·2ClO(4) (-), the dihedral angles between the fused-ring system and the pendant five- and six-membered heterocyclic rings are 6.4 (2) and 41.29 (19)°, respectively. The O atoms of both perchlorate anions are disordered over two sets of sites with occupancy ratios of 0.614 (8):0.386 (8) and 0.591 (7):0.409 (7). An intra-molecular C-H⋯N contact occurs in the cation. In the crystal, the components are linked by N-H⋯O and C-H⋯O hydrogen bonds and π-π stacking inter-actions [centroid-centroid separation = 3.642 (3) Å].

Spectroscopic and structural properties of N-(acetamide) morpholinium bromide.

A new crystal of N-(acetamide) morpholinium (NAM) bromide has been prepared in methanol at room temperature and characterized by single crystal X-ray analysis, elemental analysis, GS-MS, FTIR, NMR((1)H,(13)C, DEPTH and HETCOR). The N-(acetamide) morpholinium crystallizes in the orthorhombic crystal system, Pnma with unit cell a=12.798(9) Å, b=7.222(5) Å, c=9.244(5) Å, ß=90.00, V=854.4(9) Å(3), Z=4. The X-ray structure determination revealed that there are strong inner and intermolecular hydrogen bonds in the crystal.