Results from a cervical cancer screening program in Samsun, Turkey.

BACKGROUND: Cervical cancer is a preventable disease. This study aimed to share the results of the national cervical cancer screening program performed in primary health care institutions in Samsun between 2015 and 2019. METHODS: Women aged 30-65 years who were screened for cervical cancer in screening centers of Samsun between January 01, 2015, and December 31, 2019, were included in this descriptive study. The data were obtained from the automation program of the "National Human Papilloma Virus (HPV) Laboratory Application" used by the Provincial Directorate of Health Cancer Unit through filtering the completion time of the tests, and all results were evaluated without sampling. Thus, data were presented using descriptive statistics. RESULTS: The mean age of 89,302 women included in the cervical cancer screening program was 45.9 ± 9.0 years. Of the samples obtained from the participants, 1.0% were determined as insufficient material, 94.1% as HPV-negative, and 4.9% as HPV-positive. The most common HPV genotypes were 16, 51, 31, and 52. Of the 4337 HPV-positive women, 74.7% of the pap smear results were negative (including infection, 36.5%), and the most common premalignant lesions were atypical squamous cells of undetermined significance in 7.1% and low-grade squamous intraepithelial lesions in 6.9%. HPV 16/18 was also observed in 31.7% of HPV-positive women. Seven hundred ninety-five women were referred to a specialist physician for further examination and treatment within the scope of the screening algorithm. CONCLUSION: Detecting HPV-positivity by reaching more women within the national cervical cancer screening program's scope is vital in fighting against this disease. The effectiveness of cancer screening programs should be increased by ensuring community participation through awareness activities.

[New strategies for the prevention and control of cervical cancer in Chile.] / Nuevas estrategias de prevención y control de cáncer de cuello uterino en Chile.

OBJECTIVE: To discuss cervical cancer (CC), Human PapillomaVirus (HPV),CC control program and propose alternatives for Chile. MATERIALS AND METHODS: We analyzed the national program of CC 1966-2015 and the clinical CC guideline 2015-2020;HPV prevalence in women and in cases of CC; HPV infection and serology; the self-vaginal sample; the accuracy and cost-effectiveness of screening with HPV versus Papanicolaou,and triage options among HPV-AR positives. RESULTS: 600 women die of CC each year in Chile, mainly from low resources. Papanicolaou coverage is <70%; Papanicolaou sensitivity is much lowerthan HPV test.Change from Papanicolaou to HPV test is cost-effective. Since 2015, girls under 13 have been vaccinated against HPV. CONCLUSIONS: .There are the technical and economic conditions for a substantial improvement of CC in Chile: replacement of the Papanicolaou by HPV; screening every five years, with the option of self-sampling, and triage based on HPV 16/18 or Papanicolaou typing.

OBJETIVO: Discutir el cáncer cervicouterino (CC), el virus del papiloma humano (VPH),el programa de control del CC y proponer alternativas para Chile. MATERIAL Y MÉTODOS: Se analiza el programa nacional del CC 1966-2015 y la guía clínica 2015-2020, la prevalencia deVPH en mujeres y en casos de CC; la infección y serología deVPH; la autotoma; la precisión y rentabilidad del tamizaje con VPH contra el Papanicolaou y las opciones de triaje enVPH AR positivas. RESULTADOS: En Chile mueren 600 mujeres (principalmente de bajos recursos) al año por CC. La cobertura del Papanicolaou es <70%, sensibilidad muy inferior al test de VPH, por lo que el cambio esrentable.Desde 2015 se vacuna contraVPH a niñas menores de 13 años. CONCLUSIONES: Las condiciones técnicas y económicas existen en Chile para lograr una mejoría sustancial del CC:se sugiere el reemplazo del Papanicolaou por el examen deVPH;tamizaje cada cinco años con opción de autotoma; triaje con base en la tipificación deVPH 16/18 o Papanicolaou.

High sensitivity, loop-mediated isothermal amplification combined with colorimetric gold-nanoparticle probes for visual detection of high risk human papillomavirus genotypes 16 and 18.

High-risk human papillomavirus (HR-HPV) causes cervical cancer. HPV16 and HPV18 are the most prevalent strains of the virus reported in women worldwide. Loop-mediated isothermal amplification (LAMP) is an alternative method for DNA detection under isothermal conditions. However, it results in a turbid amplified product which is not easily detected by the naked eye. This study aimed to develop an improved technique by using gold nanoparticles (AuNPs) attached to a single-stranded DNA probe for the detection of HPV16 and HPV18. Detection of the LAMP product by AuNP color change was compared with detection by visual turbidity. The optimal conditions for this new LAMP-AuNP assay were an incubation time of 20min and a temperature of 65°C. After LAMP amplification was complete, its products were hybridized with the AuNP probe for 5min and then detected by the addition of magnesium salt. The color changed from red to blue as a result of aggregation of the AuNP probe under high ionic strength conditions produced by the addition of the salt. The sensitivity of the LAMP-AuNP assay was greater than the LAMP turbidity assay by up to 10-fold for both HPV genotypes. The LAMP-AuNP assay showed higher sensitivity and ease of visualization than did the LAMP turbidity for the detection of HPV16 and HPV18. Additionally, AuNP-HPV16 and AuNP-HPV18 probes were stable for over 1year. The combination of LAMP and the AuNP-probe colorimetric assay offers a simple, rapid and highly sensitive alternative diagnostic tool for the detection of HPV16 and HPV18 in district hospitals or field studies.

Hyperthermia Selectively Targets Human Papillomavirus in Cervical Tumors via p53-Dependent Apoptosis.

Human papillomavirus (HPV) is associated with cervical cancer, the third most common cancer in women. The high-risk HPV types 16 and 18 are found in over 70% of cervical cancers and produce the oncoprotein, early protein 6 (E6), which binds to p53 and mediates its ubiquitination and degradation. Targeting E6 has been shown to be a promising treatment option to eliminate HPV-positive tumor cells. In addition, combined hyperthermia with radiation is a very effective treatment strategy for cervical cancer. In this study, we examined the effect of hyperthermia on HPV-positive cells using cervical cancer cell lines infected with HPV 16 and 18, in vivo tumor models, and ex vivo-treated patient biopsies. Strikingly, we demonstrate that a clinically relevant hyperthermia temperature of 42 °C for 1 hour resulted in E6 degradation, thereby preventing the formation of the E6-p53 complex and enabling p53-dependent apoptosis and G2-phase arrest. Moreover, hyperthermia combined with p53 depletion restored both the cell-cycle distribution and apoptosis to control levels. Collectively, our findings provide new insights into the treatment of HPV-positive cervical cancer and suggest that hyperthermia therapy could improve patient outcomes.

Early Detection of Autism (ASD) by a Non-invasive Quick Measurement of Markedly Reduced Acetylcholine & DHEA and Increased ß-Amyloid (1-42), Asbestos (Chrysotile), Titanium Dioxide, Al, Hg & often Coexisting Virus Infections (CMV, HPV 16 and 18), Bacterial Infections etc. in the Brain and Corresponding Safe Individualized Effective Treatment.

A brief historical background on Autism & some of the important symptoms associated with Autism are summarized. Using strong Electro Magnetic Field Resonance Phenomenon between 2 identical molecules with identical weight (which received U.S. Patent) non-invasively & rapidly we can detect various molecules including neurotransmitters, bacteria, virus, fungus, metals & abnormal molecules. Simple non- invasive measurement of various molecules through pupils & head of diagnosed or suspected Autism patients indicated that in Autism patients following changes were often found: 1) Acetylcholine is markedly reduced; 2) Alzheimer's disease markers (i.e. ß-Amyloid (1-42), Tau Protein, Apolipoprotein (Apo E4)) are markedly increased; 3) Chrysotile Asbestos is increased; 4) Titanium Dioxide (TiO2) is moderately increased; 5) Al is moderately increased; 6) Hg is moderately increased; 7) Dopamine, Serotonin & GABA are significantly reduced (up to about 1/10 of normal); 8) Often viral infections (such as CMV, HHV-6, HPV-16, HPV-18, etc.), and Bacterial infections (such as Chlamydia trachomatis, Mycobacterium TB, Borrelia Burgdorferi, etc.) coexist. Research by others on Autism spectrum disorder (ASD) shows that it is a group of complex neurodevelopmental disorders, with about 70% of ASD patients also suffering from gastro-intestinal problems. While Alzheimer disease (AD) is characterized by formation of 1) Amyloid plaques, 2) Neurofibrillary tangles inside of neurons, and 3) Loss of connections between neurons. More than 90% of AD develops in people over the age of 65. These 3 characteristics often progressively worsen over time. Although Autism Spectrum Disorder and Alzheimer's disease are completely different diseases they have some similar biochemical changes. Eight examples of such measurement & analysis are shown for comparison. Most of Autism patients improved significantly by removing the source or preventing intake of Asbestos, TiO2, Al & Hg or enhancing urinary output of above abnormal substances & coexisting infections, if treatment is given early. When HPV-16 & HPV-18 coexist, at triangular central area of the top of head, in addition to inability to talk, severe neuromuscular problems of lower extremity were found to also exist. However, if treatment is given 3-4 years after onset of Autism symptoms, even when successful biochemical reduction of above abnormal substances occurs, clinical improvement is less significant, since permanent damage in brain tissue seems to already exist. Therefore, early diagnosis & early treatment is very important for both Autism & Alzheimer's disease. In addition the optimal doses of Vitamin D3 and Taurine may play an important role in the future treatment of Autism, Alzheimer's Disease and memory disturbances by significantly increasing Acetylcholine and DHEA levels, enhancing the excretion of toxic substances in the urine, as well as having an anticancer effect.

The aqueous extract of Ficus religiosa induces cell cycle arrest in human cervical cancer cell lines SiHa (HPV-16 Positive) and apoptosis in HeLa (HPV-18 positive).

Natural products are being extensively explored for their potential to prevent as well as treat cancer due to their ability to target multiple molecular pathways. Ficus religiosa has been shown to exert diverse biological activities including apoptosis in breast cancer cell lines. In the present study, we report the anti-neoplastic potential of aqueous extract of F. religiosa (FRaq) bark in human cervical cancer cell lines, SiHa and HeLa. FRaq altered the growth kinetics of SiHa (HPV-16 positive) and HeLa (HPV-18 positive) cells in a dose-dependent manner. It blocked the cell cycle progression at G1/S phase in SiHa that was characterized by an increase in the expression of p53, p21 and pRb proteins with a simultaneous decrease in the expression of phospho Rb (ppRb) protein. On the other hand, in HeLa, FRaq induced apoptosis through an increase in intracellular Ca(2+) leading to loss of mitochondrial membrane potential, release of cytochrome-c and increase in the expression of caspase-3. Moreover, FRaq reduced the migration as well as invasion capability of both the cervical cancer cell lines accompanied with downregulation of MMP-2 and Her-2 expression. Interestingly, FRaq reduced the expression of viral oncoproteins E6 and E7 in both the cervical cancer cell lines. All these data suggest that F. religiosa could be explored for its chemopreventive potential in cervical cancer.

More than 97% of human papilloma virus type 16 (HPV-16) was found with chrysotile asbestos & relatively smooth round tumor outline, and less than 3% was found with HPV-18 and tremolite asbestos & irregular sawtooth-like zigzag outline in breast cancer tissues in over 500 mammograms of female patients: their implications in diagnosis, treatment, and prevention of breast cancer.

In the past, Human Papillomavirus Type 16 (HPV-16) was considered to be the main cause of cancer in the oropharynx and genital organs. Cervical cancer of the uterus is the most well-known cancer associated with HPV-16. Among the oncogenic HPVs, types 16 and 18 are most responsible for the majority of the HPV-caused cancers. Recently, using EMF Resonance Phenomenon between 2 identical substances, we non-invasively measured HPV-16 and HPV-18 among 25 physicians and 25 dentists and found that all 50 have HPV-16 in oral cavities and oropharynx but not HPV-18. However most dentists have a stronger infection than physicians. Among them were 2 female dentists with breast cancer containing HPV-16 and strong infections of HPV-16 in the oral cavities and oropharynx. When the author checked their breast cancer positive areas as well as the mammograms of cancer positive areas, Chrysotile Asbestos co-existed with an infection of HPV-16. We then examined over 500 published mammograms of women with malignant breast cancer published by other institutes, and we found HPV-16 in more than 97% and HPV-18 in less than 3% of the breast cancer mammograms examined. Less than 0.4% of cases were found as a variety of combination of HPV-16 & HPV-18. We also discovered that breast cancer with HPV-16 always co-exists with increased Chrysotile Asbestos deposits, and the outline of the breast cancer positive area is a relatively smooth and round or oval shape, and breast cancer with HPV-18 always co-exists with increased Tremolite Asbestos, where the tumor outline is an irregular saw-tooth like zigzag pattern. Based on these findings, better methods of diagnosis, treatment and prevention with a vaccine can be developed.

Overexpression of VEGF and TGF-beta1 mRNA in Pap smears correlates with progression of cervical intraepithelial neoplasia to cancer: implication of YY1 in cervical tumorigenesis and HPV infection.

The screening of neo-angiogenesis related gene expression has uncovered many disrupted molecular pathways which may significantly confer to malignant transformation of various cell types including cervical cells. The objective of the present study was to delineate whether changes in certain gene expression profiles during the malignant conversion of the uterine cervix can be potentially used to predict the clinical course and outcome of the cervical pathology. Total RNA was isolated from Pap smears obtained from healthy females or patients diagnosed with low-grade squamous cervical intraepithelial lesions (LG-SIL), high-grade (HG)-SIL or cervical carcinoma. VEGF, TGF-beta1 and YY1 mRNA expression levels were assessed by QRT-PCR. Confirmation of YY1 protein discrepancy among cervical tissues of different histopathology was performed by immunohistochemistry. All tested genes showed statistically significant expression variations among the indicated groups. VEGF and TGF-beta1 mRNA overexpression was found to be associated with progression from low-grade to high-grade cervical intraepithelial neoplasia (CIN), while YY1 showed constitutively elevated transcript levels in CIN and cervical cancer compared to controls. At the protein level YY1 was also overexpressed in HG-SIL and cancer tissues compared to LG-SIL. Both YY1 transcript and protein overexpression were associated with HPV18- or HPV16-infected samples. Spearman analysis revealed a co-expression pattern for VEGF and TGF-beta1 mRNAs in normal cervix and LG-SIL; however, YY1 expression correlated negatively with VEGF and TGF-beta1 transcript levels upon the onset of the cervical neoplastic transformation. Our findings provide for the first time evidence for the implication of YY1 in uterine cervix carcinogenesis and suggest that VEGF, TGF-beta1 and YY1 could be useful biomarkers of cervical malignant transformation as well as potential targets for therapeutic approaches.