Ca Cx Research Articles

Comparative analysis of different cervical screening methods with special reference to the WHO recommended human papillomavirus detection at a rural tertiary care center - A pilot study

Background: Cervical cancer (Ca Cx) the 4th common cancer has a high mortality rate. Human Papilloma Virus (HPV) is chiefly responsible for a long latent period to progress from preinvasive to invasive Ca Cx. So it can be prevented by screening procedures such as visual inspection with acetic acid (VIA), conventional cervical PAP smear (CP), liquid-based cytology (LBC), and high-risk (HPV-hr) detection along with vaccination. Aims and Objectives: The study aims to determine the socio-demographic profile of Ca Cx and the most appropriate cost-effective community screening method. Materials and Methods: A prospective observational study with 80 symptomatic women of reproductive and peri/postmenopausal age groups attending the Gynecology Department who underwent VIA, CP, and LBC and thereby detected positive along with screened negative but clinically suspicious women were tested for HPV-hr detection. Results were tabulated into an Excel sheet and screening methods were compared using Chi-square test, gold standard being cervical histopathology (P<0.5 significant). Statistical software used - Graphpad Prism 9 (San Diego, CA). Results: The mean age was 43.3 years. Multiparity and early marriage were seen in 80% and 45% respectively. Inflammatory lesions were best diagnosed by CP but epithelial cell abnormality and more satisfactory smears by LBC (P<0.05). Sensitivity was highest (93.75%) in VIA, positive predictive value, and specificity in CP (91.66%, 75%). negative predictive value was highest in VIA and HPV-hr DNA (50%). Conclusion: VIA with CP/LBC is an economically viable and effective screening method for Ca Cx in developing countries along with HPV vaccination.

Dosimetric evaluation of 6 MV and 18 MV intensity-modulated radiotherapy plans for treatment of carcinoma of the cervix

Introduction: Cervical cancer (Ca Cx) is the fourth most frequent cancer in women with an estimated 57000 new cases in 2018 representing 6.6% of all female cancers. Approximately 90% of deaths from cervical cancer occurred in low- and middle-income countries. Material and Methods: A retrospective radiotherapy treatment planning comparative study conducted at the Department of Radiation Physics, Kidwai Memorial Institute of Oncology, Bangalore during June 2018- March 2019. Result: All the plans were normalized to 100 % at Target mean to achieve a similar target dose for quantitative comparison of DVHs. The results for target coverage, OAR sparing, integral dose, and monitoring units. Conclusions: The tradeoff of using 6 MV and 18 MV for cervix patients depends on many parameters. Since the same PTV coverage was forced for both energies by having the same optimization constraints, there was little difference in target coverage and conformity index for both energies.

Chemoradiation in locally advanced Ca Cx: Effect on NGAL levels.

Neutrophil gelatinase-associated lipocalin (NGAL) has been reported to be unregulated in many cancers and to suppress tumor suppressor genes like p53 leading to cell proliferation. Studies to report its relationship with carcinoma cervix (Ca Cx) are still scant. Serum NGAL levels were analyzed in 30 patients of histopathologically proven locally advanced Ca Cx at the time of diagnosis and 3 weeks after standard chemoradiation by enzyme-linked immunosorbent assay. These patients underwent either brachytherapy or supplementary external beam radiotherapy (EBRT) depending on the response of treatment. The results were analyzed statistically by applying Student's paired t-test. No statistically significant difference (P > 0.05) was observed in patients of Ca Cx before and after treatment or when compared stage wise, histopathological grade wise, or response wise. But the levels were found to increase when duration of treatment was ≥8 weeks (P = 0.040) and to decrease significantly when duration of treatment was <8 weeks (P = 0.0052). The NGAL levels also increased significantly after treatment in patients who received EBRT and supplementary radiotherapy (P = 0.019) while the pre- and post-treatment difference in NGAL levels was not statistically significant in patients who received EBRT + intracavitary brachytherapy (P > 0.05). As the duration as well as modality of treatment is quite important in Ca Cx, shorter duration associated with better results and lower NGAL levels, NGAL might prove to be a useful biomarker although further studies are needed to support the claim.

Dosimetric analysis of Co-60 source based high dose rate (HDR) brachytherapy: A case series of ten patients with carcinoma of the uterine cervix

AimTo analyse the dosimetric parameters of Co-60 based high dose rate (HDR) brachytherapy plans for patients of carcinoma uterine cervix. BackgroundCo-60 high dose rate (HDR) brachytherapy unit has been introduced in past few years and is gaining importance owing to its long half life, economical benefits and comparable clinical outcome compared to Ir-192 HDR brachytherapy. Materials and methodsA study was conducted on ten patients with locally advanced carcinoma of the uterine cervix (Ca Cx). Computed tomography (CT) images were taken after three channel applicator insertions. The planning for 7 Gray per fraction (7Gy/#) was done for Co-60 HDR brachytherapy unit following the American Brachytherapy Society (ABS) guidelines. All the patients were treated with 3# with one week interval between fractions. ResultsThe mean dose to high risk clinical target volumes (HRCTV) for D90 (dose to 90% volume) was found to be 102.05% (Standard Deviation (SD): 3.07). The mean D2cc (dose to 2 cubic centimeter volume) of the bladder, rectum and sigmoid were found to be 15.9Gy (SD: 0.58), 11.5Gy (SD: 0.91) and 4.1Gy (SD: 1.52), respectively. ConclusionThe target coverage and doses to organs at risk (OARs) were achieved as per the ABS guidelines. Hence, it can be concluded that the Co-60 HDR brachytherapy unit is a good choice especially for the centers with a small number of brachytherapy procedures as no frequent source replacement is required like in an Ir-192 HDR unit.

Cervical cancer screeningnin Chittagong Medical College Hospital: bottleneck of service delivery system of a referral centre in Bangladesh

Bangladesh is overburdened with cervical cancer. In each year 13,000 new cases enter in this series. Visual inspection of cervix with acetic acid (VIA) is adopted as national cervical cancer (ca cx) screening program, in Bangladesh. Positive VIA, abnormal cytology, positive HPV or suspicious looking cervices are referred for secondary screening (Colposcopy). Chittagong Medical College Hospital (CMCH) acts as a primary screening and secondary referral center. With the aim to identify the weakness of present ca cx screening system one year (April 2013 to March 2014) records were evaluated. A total 1853 VIA &amp; 714 colposcopy cases were analyzed from records of CMCH, Bangladesh. The age of population range from 16 -71 years and most were between 30-49 years. In primary screening VIA +ve cases were 6% (n=120). After secondary screening 43.69% (n=312) were identified as abnormal; among those precancerous lesion (CIN) 37.82% (n= 270); ca cx 1.54% (n=11); suspicious 4.34% (n=31). Histopathology proven CIN 12.04% (n=86) &amp; ca cx 2.10% (n=15). Cases received treatment (LEEP) were only 09.38% (n=67). Finally among total population, 56.30% (n=402) were declared normal, 14.15% (n=101) had definite pathology and 29.55% (n=211) remained undetermined (as they failed to re-produce their histology report at the final step of secondary screening). This study found a bottleneck caused by present service delivery systems; lack of prompt referring and re-reporting to primary center within a schedule time (after receiving management) and lack of recall system both from primary and secondary screening center. To make the program successful have to have schedule for re-reporting and recalling.DOI: http://dx.doi.org/10.3329/bjpp.v30i1.20790 Bangladesh J Physiol Pharmacol 2014; 30(1):25-28

English

BACKGROUND: Palliation reduces the severity of disease symptoms, rather than reversing its progression or providing a cure. Metastatic cancer cervix (Ca Cx) is incurable by surgery, radiation or chemotherapy, but these modalities are useful for palliation. Globally about five to six lakh new cases of carcinoma cervix are diagnosed every year. Of these, one lakh cases are diagnosed in India of which 25.0% are from West Bengal only. OBJECTIVES: Our objective was to study the role of palliation in Stage IV Carcinoma Cervix. SETTINGS AND DESIGN: During the study period of five years from January 2007 to December 2011, consecutive seventy five new cases of stage IV carcinoma cervix diagnosed at Netaji Subhas Chandra Bose Cancer Research Institute, Kolkata, were included in our study. MATERIALS AND METHODS: Clinical examination with relevant investigations like kidney function tests (KFT), biopsy, cystoscopy, CT scan etc were done for diagnosis & staging. Treatment was decided based on woman's age, general health and the location & type of the tumour. Treatment options were surgery, radiotherapy (RT), chemotherapy (CT) and simple palliation. In our study, combined CT+RT was done in 18.67% patients most of who presented with Stage IV disease. Radiation was given as brachytherapy following teletherapy. Chemotherapy was used as adjunct to RT or for palliation or as neo-adjuvant chemotherapy (NACT), most commonly using paclitaxel (135mg/square metre), cisplatin (50mg/ square metre) and 5fluorouracil (600mg/ square metre). At times, chemotherapy could provide pain relief only. Vault smear and metastatic workup was done during follow-up visits every 8-12 weeks after treatment completion. RESULTS: Majority of patients belonged to the age group 42-69 years with a median age of 53 years. Bladder involvement was seen in 15(20.0%) cases, bowel involvement in 14(19.0%) and distant metastasis in 46(61.0%) cases. Most cases were of Squamous cell carcinoma (94.0%), clinically presenting with foul smelling vaginal discharge ± bleeding per vaginum (100.0%). In our study, significant amount (30.0%) of disease control for a substantial period (1.5 years) was observed. The overall survival rate in patients of Stage IV carcinoma cervix on various forms of palliative treatment was 18.0%. CONCLUSION: Palliation is achieved by surgery, radiation or chemotherapy, though at times, simple palliation is the only feasible option. The poor survival rate was probably due to improper reporting & lack of regular follow up in the given socio-economic background. As cure cannot be achieved in advanced carcinoma cervix, palliation is important in alleviating the distressing symptoms and improving the quality of life.

Glucose-dependent insulinotropic peptide receptor expression in the hippocampus and neocortex of mesial temporal lobe epilepsy patients and rats undergoing pilocarpine induced status epilepticus

The glucose-dependent insulinotropic peptide receptor (GIPR) has been implicated with neuroplasticity and may be related to epilepsy. GIPR expression was analyzed by immunohistochemistry in the hippocampus (HIP) and neocortex (Cx) of rats undergoing pilocarpine induced status epilepticus (Pilo-SE), and in three young male patients with left mesial temporal lobe epilepsy related to hippocampal sclerosis (MTLE-HS) treated surgically. A combined GIPR immunohistochemistry and Fluoro-Jade staining was carried out to investigate the association between the GIPR expression and neuronal degeneration induced by Pilo-SE. GIPR was expressed in the cytoplasm of neurons from the HIP CA subfields, dentate gyrus (DG) and Cx of animals and human samples. The GIPR expression after the Pilo-SE induction increases significantly in the HIP after 1 h and 5 days, but not after 12 h or 50 days. In the Cx, the GIPR expression increases after 1 h, 12 h and 5 days, but not 50 days after the Pilo-SE. The expression of GIPR 12 h after Pilo-SE was inversely proportional to the Fluoro-Jade staining intensity. In the human tissue, GIPR expression patterns were similar to those observed in chronic Pilo-SE animals. No Fluoro-Jade stained cells were observed in the human sample. GIPR is expressed in human HIP and Cx. There was a time and region dependent increase of GIPR expression in the HIP and Cx after Pilo-SE that was inversely associated to neuronal degeneration.

A dosimetric analysis of 6 MV versus 15 MV photon energy plans for intensity modulated radiation therapy (IMRT) of carcinoma of cervix

Background Intensity modulated radiotherapy (IMRT) is being used to treat carcinoma of cervix (Ca Cx). Integral dose to normal tissue and increased leakage are the concern about IMRT. 6 MV photon beam is a good choice of energy for Ca Cx IMRT treatment. Aim The objective of this study was to compare intensity modulated radiotherapy (IMRT) plans generated by 6 MV and 15 MV photon energies for carcinoma of cervix (Ca Cx) with regards to dosimetric parameters of planning target volume (PTV) and organs at risk (OAR), homogeneity index (HI), conformity index at 98% level (CI 98%), integral dose to normal tissue (NTID) and total number of monitor units (MUs). Material and methods A cohort of 16 patients was selected for this study. All patients were to receive a dose of 50 Gy in 25 fractions. IMRT plans were generated for both energies using same dose–volume constraints. Results Our results show a comparable coverage of planning target volume (PTV) for both energies. Volume of PTV receiving a prescription dose is 97.8 ± 0.5% and 98.8 ± 0.4% for the 6 MV and the 15 MV plans. Volume of PTV receiving a dose of 107% is 4.4 ± 7.8% and 16.1 ± 22.2%. Bladder and rectum mean doses for the 6 MV and the 15 MV photon plans were 39.8 ± 3.0 Gy and 40.0 ± 3.2 Gy, and 35.8 ± 3.1 Gy and 36.0 ± 3.1 Gy, respectively. Homogeneity index (HI) for both energies was 1.04. The conformity indices at 98% isodose (CI 98%) were 1.3 ± 0.1 and 1.4 ± 0.1 for 6 MV and 15 MV photon plans, respectively. Conclusions We conclude that a 6 MV photon is a good choice for Ca Cx IMRT as it produces a highly conformal, homogeneous plan with superior target coverage and better OAR sparing.

Lipid peroxidation and antioxidants in different stages of cervical cancer: Prognostic significance

Free radical Injury is associated with cancer, but how the extent of oxidative stress correlates with the FIGO (International Federation of Gynecology and Obstetrics) stage in Carcinoma Cervix (Ca Cx), and its significance as a prognostic marker, is not clear and needs an in-depth study. To correlate the blood levels of Lipid Peroxidation (LPO), Reduced Glutathione (GSH), Superoxide Dismutase (SOD), and Vitamin A and E levels with the clinical stage in Ca Cx. This is a Prospective Case Control Study. LPO, SOD, reduced GSH were estimated by Bio Chemical Assays and Vitamins by High Performance Liquid Chromatography (HPLC). The cases and controls were compared using One Way ANOVA and different stages over different time periods were individually compared by Repeated Measure Analysis of Variance. The results indicated a statistically significant increase of LPO vis-a-vis the FIGO stage of Ca Cx and control, while the antioxidant status as depicted by GSH and SOD decreased. Vitamin A and E levels were significantly lower in cancer cases as compared to the control. Increased LPO and reduced antioxidant levels may be taken as associated predictive markers, thus suggesting that Ca Cx cases should get nutritive supplements to contain the blood LPO level and maintain a positive balance of antioxidants for a better outcome in terms of delayed recurrence and better Quality of Life (QOL).

Peripheral blood lymphocyte subpopulations in patients with cervical cancer

Objective Impairment of cell-mediated immunity in carcinoma of the cervix (CA CX) and cervical intraepithelial neoplasia (CIN) are reported. Contradictory reports exist on lymphocyte subpopulations associated with this disease. The present study aims to quantitatively analyze peripheral blood lymphocytes subsets in patients with CA CX and CIN. Method Systemic T lymphocyte subsets, CD19+, CD16+ and CD56+ cells in 58 CA CX and 10 CIN patients were studied. The lymphocyte phenotypes were quantified by monoclonal antibodies (anti-CD4, CD8, CD16, CD19 and CD56). Result Significant decrease in CD4+ cell population was observed in CA CX and CIN patients as compared to controls ( P ≤ 0.05). CD4+/CD8+ ratio was observed to be less in CIN patients ( P ≤ 0.001). Other lymphocyte subpopulations appeared to be comparable between the groups. Conclusion Results indicate immunological abnormalities in invasive CA CX and CIN patients. Study on a larger patient population may provide a biomarker for early detection of this disease.

A randomized trial of hydroxyurea (HD) vs misonidazole (Mi) adjunct to radiation therapy in Stages IIB, III, and IVA carcinoma of the cervix (CA CX): A gynecologic oncology group study

A randomized trial of hydroxyurea (HD) vs misonidazole (Mi) adjunct to radiation therapy in Stages IIB, III, and IVA carcinoma of the cervix (CA CX): A gynecologic oncology group study

Para-aortic lymph node irradiation in carcinoma of the cervix after exploratory laparotomy and biopsy-proven positive aortic nodes

From July 1970 to January 1977, 23 patients with previously untreated cancer of the cervix (CA CX), mostly Stage IIIB, were included in this study. The pare-aortic lymph nodes (PALN) were histologically documented to have metastatic disease in all 23 patients. External radiation treatment (RT) was delivered using a Colbalt—60 machine to a spade-shaped field to treat the pelvic cavity and para-aortic area. The majority of the patients received 4000–6000 rad to the pelvic cavity and from 5000–5500 rad to the PALN's by external RT. In addition, intracavitary radium was used in 21 patients. Five patients are alive and free of disease at 115, 110, 90, 73 and 45 months after completion of RT. One survivor had clinical Stage IB, one had Stage IIB, and three had Stage IIIB cervical carcinoma. Two of 15 patients with clinically enlarged and suspicious para-aortic nodes are alive, while 3 of 8 patients with clinically normal appearing nodes survived. Three (60%) of the survivors developed late bowel radiation damage. Eighteen patients died—10 during the first year, 3 during the second year, 2 during the third year, 1 during the fourth year and 2 during the eighth year of the follow-up. Five (27.8%) of the patients who died had developed late bowel radiation damage. Fifteen of the 18 died with disease at an average of 21 months. Three patients died of intercurrent disease. Their average survival was 40 months, double that of patients dying of disease. This report suggests that in cancer of the cervix, radiation therapy can control some PALN metastatic disease, but the risk of complications is rather high. In the absence of better methods of management, this risk of complications is justifiable because the alternative is to leave known disease untreated.

Humoral- and cell-mediated immune responses to herpesvirus antigens in patients with cervical carcinoma

The humoral and cellular immune responses were studied in 35 patients with cervical carcinoma (Ca Cx) and 32 healthy controls. Complement fixing (CF) and indirect hemagglutinating antibody (IHA) titers for herpes simplex type 1 (HSV-1), herpes simplex type 2 (HSV-2), and cytomegalovirus (CMV), and fluorescent antibody (FA) titers for viral capsid antigen for Epstein-Barr virus (EBV) were determined. Cellular immune response was measured by the technique of [ 3H]thymidine uptake by stimulated lymphocytes. Phytohemagglutinin (PHA), HSV-1, HSV-2, and CMV antigens were used as stimulants. CF titers (≥ 1:4) to HSV-1, HSV-2, and CMV were present in 34 ( P < 0.005), 33 ( P < 0.005), and 29 Ca Cx patients and in 22, 20, and 18 controls. IHA titers (≥ 1.8) to HSV-1 and HSV-2 were present in all 35 Ca Cx patients ( P < 0.0001) and only 20 and 19 controls, respectively. IHA titers for CMV and FA titers for EBV were not different in the two study groups. Significantly more Ca Cx patients demonstrated definite prior HSV-2 infection ( P < 0.002). Geometric means of IHA titers were higher for HSV-1 ( P < 0.01) and HSV-2 ( P < 0.005) antigens in Ca Cx patients. Lymphocyte stimulation indices of 3 or greater, indicative of cell-mediated immunity, were found in all 35 Ca Cx patients to HSV-1 ( P < 0.0005), HSV-2 ( P < 0.0002) antigens, and in only 21 and 20 controls, respectively. A significantly increased lymphocyte response to a 1 100 dilution of HSV-2 antigen with other data suggests a difference in past exposure or an altered response of lymphocytes to HSV-2 antigen in Ca Cx patients.

Detection of Characteristic Differences in the Irradiation Sensitivity of Four Human Cancer Cell Strains

Monolayers of four human cancer cell strains were exposed to various doses of x radiation during different phases of their growth cycles. The effects as measured by changes in cell number were dependent on the radiation dose. The dose-response curve of each strain varied significantly when radiation was administered during different stages of the population cycle. With three strains, HeLa, RP Ca Vu I, and RP Ca Ov I, the cells at the beginning of the logarithmic growth phase were more sensitive to radiation than cells entering the negative growth acceleration phase. With the other strain, RP Ca Cx I, the reverse was true. Highly significant differences in the radiation sensitivity of the four cell lines were detected when radiation was administered during the fourth culture day, a period when the cells were entering the phase of negative growth acceleration. The characteristic differences appear to be consistent with the generally accepted radiotherapeutic susceptibility of the tumors from which the cell lines were originally derived. (auth)