Journal

Journal of the Pakistan Medical Association

Papers (32)

Meta-analysis about correlation between the human Papillomavirus infection and the incidence of cervical intraepithelial Neoplasia

Objective: To determine the correlations between human papillomavirus infection and the incidence of cervicalintraepithelial neoplasia.Method:This study was conducted in the Affiliated Hospital of Zunyi Medical University, Zunyi, China in January 2024. Thesystematic review and meta-analysis comprised literature search on PubMed, Medline, Embase, Cochrane Library, Web ofScience, China Biomedical and Wanfang databases for studies published from January 2010 to December 2020 related tohuman papillomavirus and cervical intraepithelial neoplasia. The quality of the studies was evaluated using the Newcastle-Ottawa Scale, and meta-analysis was done using RevMan 5.3.Results: Of the 854 studies identified, 10(1.2%) were included; 7(70%) in English and 3(30%) in Chinese. There was a totalof 193,000 patients; 94,298(49%) in the observation group and 98,702(51%) in the control group. Human papillomavirusinfection was closely correlated with cervical intraepithelial neoplasia-1, cervical intraepithelial neoplasia-2 and cervicalintraepithelial neoplasia-3 in women, with odds ratios of 3.94 (95% confidence interval: 3.53-4.40), 1.03 (95% confidenceinterval: 1.01-1.06) and 1.13 (95% confidence interval: 1.10-1.16), respectively. Both human papillomavirus single infectionand reinfection in cervical intraepithelial neoplasia patients were significantly higher than in normal women, with oddsratios of 0.50 (95% confidence interval: 0.41-0.61) and 0.43 (95% confidence interval: 0.35-0.53), respectively.Conclusion: The incidence of cervical intraepithelial neoplasia was found to be highly associated with human papillomavirusinfection, and the infection increased the risk of cervical diseases.Keywords: Human papillomavirus, HPV infection, Cervical intraepithelial neoplasia, CIN, Cervical diseases, Meta-analysis.

Comparison of serum Vascular Cell Adhesion Molecule (VCAM) level among epithelial ovarian cancer patients and healthy women

Objective: To compare serum vascular cell adhesion molecule levels among ovarian cancer patients of different standardised grades, and in relation to healthy controls. Method: The case-control study was conducted from 6.2.2018 to 1.8.2021 after approval form the ethics review board of the University of Health Sciences, Lahore, Pakistan, and comprised females aged 20-70 years diagnosed with ovarian cancer and tentatively planned for surgical procedures in group A, and healthy controls in group B. From all the subjects, 2.5ml blood was taken in a green-top tube. The tubes were centrifuged, and the serum was separated within an hour of sample collection. The Eppendorf tubes were labelled and stored at -20°C. The samples were thawed, and, following the manual protocol, they were subjected to vascular cell adhesion molecule enzyme-linked immunosorbent assay. Cancer antigen 125 values before surgery and 6-8 months post-surgery were recorded from available laboratory reports. Also, group A was categorised in line with the International Federation of Gynaecology and Obstetrics stage classification. Data was analysed using SPSS 24. Results: Of the 80 female subjects, 40(50%) were group A cases and 40(50%) were group B controls. The overall mean age was 48±12 years. Overall, 55(68.7%) women were aged <55 years and 25(31.3%) were aged >55 years. Within group A, 20(50%) had cancer stage I-II and 20(50%) had stage III-IV. Overall median vascular cell adhesion molecule was 72.40ug/L (interquartile range: 1857.40ug/L), with 71.15ug/L (interquartile range: 616.60ug/L) in group A and 74.10ug/L (interquartile range: 1848.70ug/L) in group B. Significant correlation was found between cancer stage and vascular cell adhesion molecule level (rho=0.73; p=0.003). Conclusion: There was a decreased level of vascular cell adhesion molecule level in epithelial ovarian cancer cases compared to healthy controls. A positive association was observed between ovarian cancer stage and vascular cell adhesion molecule level. Key Words: VCAM, FIGO, Correlation, Serum marker, Ovarian cancer.

Dostarlimab A new hope for endometrial cancer patients in Pakistan

Endometrial cancer (EC) is the most common gynaecological cancer in Pakistan, with an estimated incidence of 7.4 per 100,000 women [1]. It is a disease where cancer cells grow in the lining of the uterus (endometrium). EC can be classified into two types based on the genetic features of the cancer cells: mismatch repair deficient (dMMR) or microsatellite instability-high (MSI-H), and mismatch repair proficient (pMMR) or microsatellite stable (MSS). The former type accounts for about 20-30% of EC cases and has a worse prognosis than the latter [2]. Dostarlimab is a monoclonal antibody that blocks a protein called PD-1 on immune cells. The immune system is often restrained by PD-1, which stops it from targeting healthy cells. However, some cancer cells can exploit this mechanism by producing proteins (PD-L1 and PD-L2) that bind to PD-1 and switches off the immune response. By blocking PD-1, Dostarlimab restores the immune system’s ability to recognise and kill cancer cells [3]. Dostarlimab has been approved by the US Food and Drug Administration (FDA) and the European Medicines Agency (EMA) for the treatment of adults with dMMR/MSI-H recurrent or advanced EC that has progressed on or following prior treatment with a platinum-containing regimen [4,5]. Clinical studies have shown positive results for Dostarlimab in this patient population. In the GARNET trial, Dostarlimab achieved an objective response rate (ORR) of 43.5%, meaning that 43.5% of patients had their tumours shrink or disappear after treatment [3]. The median duration of response (DOR) was not reached, indicating that most responses persisted [8]. The most common side effects of Dostarlimab were fatigue, nausea, diarrhoea, anaemia, and constipation [5]. Dostarlimab offers new hope for endometrial cancer patients in Pakistan who have limited treatment options and poor outcomes. It is a targeted therapy that harnesses the power of the immune system to fight cancer. It is also a convenient and well-tolerated treatment that can be administered every 3 or 6 weeks as an intravenous infusion [2,3]. Dostarlimab is not yet available in Pakistan, but efforts are underway to bring it to the country as soon as possible. Dostarlimab has the potential to improve the quality of life and survival of endometrial cancer patients in Pakistan who have dMMR/MSI-H tumours.

Cervical cancer screening practices in HIV positive females – a missing link in health care delivery in Pakistan

Objective: To probe cervical cancer screening practices in local women positive for human immunodeficiency virus, and to determine the cervical cytological changes in them. Method: The serial cross-sectional study was conducted at the Jinnah Hospital and Services Hospital, Lahore, Pakistan, from April 2019 to October 2020, and comprised female patients aged 18-45 years who were positive for human immunodeficiency virus or acquired immunodeficiency syndrome and were registered with the relevant programme being run by the provincial government in Punjab. Blood samples of all the patients were collected for the determination of human immunodeficiency virus viral load and cluster of differentiation 4+ count. Cervical smears were taken for cytopathological analysis, while the swabs were analysed for culture sensitivity. The same individuals were subjected to the same testing one year later, and the status of the disease and clinical stability or disease progression was explored. Data was analysed using SPSS 25. Results: There were 150 women with mean age 32.08±7.13 years (range: 21-45 years). Age at marriage/sexual activity was 17.33±4.73 years in 15(10%) subjects. Cytological examination showed atypical squamous cells of undetermined significance in 6(4%) of the cases whereas 3(2%) cases showed atypical squamous cells, which cannot rule out high grade squamous intraepithelial lesion on cytology, while the rest were classified as negative for intraepithelial lesion or malignancy. Cervical microbial changes revealed methicillin-resistant staphylococcus aureus infection in 9(6%) cases, extended-spectrum beta-lactamase in 15(10%) cases, whereas fungal infection and trichomonas vaginalis infection were found in 30(20%) smears. There was a significant association between cluster of differentiation 4+ cell count and stability of high-risk patients (p<0.001). After one year, 84(56%) patients remained clinically stable, while 51(34%) developed some chronic illness. There was a significant association between cluster of differentiation 4+ cell count <200/mm 3 and the risk of developing a chronic illness (p<0.001). Conclusion: There was a dire need to educate healthcare workers to offer regular cervical screening to patients with high-risk sexually-transmitted infections to prevent them from the morbidity and mortality related to cervical cancer. Key Words: HIV/AIDS, Cervical cancer, Screening, Bethesda system.

Frequency of human papilloma virus (HPV) vaccination among female health care providers and reasons for non-immunization at a public sector hospital

Objective: To assess the knowledge and attitude of female healthcare providers about human papilloma virus and its vaccination, to determine the frequency of respondents vaccinated against the virus, and to evaluate the reasons for non-immunisation. Method: The cross-sectional study was conducted at the Jinnah Hospital, Lahore, Pakistan, from January 7 to February 20, 2022, and comprised female health care providers aged 20-60 years. Data was collected using a self-assessing questionnaire. Data was analysed using SPSS 22. Results: Of the 250 individuals approached, 210(84%) took part in the study. The mean age was 28.9+/-7.99 years. Most of the subjects were house officers, medical officers or senior registrars 138(65.7%), and 126(60%) were unmarried. Overall, 170(81%) respondents knew about human papilloma virus and 174(82.9%) were aware of its link with cervical cancer. Even though 128(61%) respondents knew that the virus can be prevented by vaccine, 14(6.7%) were actually vaccinated. The vaccinated individuals had better knowledge about HPV, its spread, complications, its association with cervical cancer, prevention by vaccination and availability of vaccine compared to the non-vaccinated (p =0.05) Conclusion: The trend of human papilloma virus vaccination among female health professionals was found to be low, and lack of awareness and counselling was the leading cause. Key Words: Human papillomavirus, Cervical cancer, Vaccination.

Role of serum VEGF-A biomarker for early diagnosis of ovarian cancer instead of CA-125

Objective: Vascular Endothelial Growth Factor-A (VEGF-A) is one of the most potent modulator and prominent mediator of angiogenesis and neovascularization. Present study focuses on the significance of VEGF-A as potential biomarker from serum for the diagnosis of non-therapeutic, pre-operative ovarian cancer patients in comparison with healthy individuals instead of Cancer Antigen-125 (CA-125). Methods: The study recruited total 89 subjects; 44 cases of epithelial ovarian cancer (31 malignant and 13 benign) and 45 healthy female controls under aseptic conditions. Serum VEGF-A and CA-125 levels were evaluated from each subject using Luminex multi-analyte profiling (xMAP) technology on BioPlex instrument and EIA technique, respectively. Different clinicopathological parameters; age, stage, grading, metastasis and ascites of ovarian cancer patients were investigated and compared with serum VEGF-A and CA-125 levels. Results: Our results showed that serum VEGF-A values were inversely proportional to the stage of ovarian cancer. However, steadily increase in the CA-125 values was observed with progression of the disease. Conclusion: The detection of highest concentration of serum VEGF-A level in FIGO (International Federation of Gynecology and Obstetrics) stage-I suggests its use as one of the diagnostic parameter in the timely investigation of ovarian cancer. Keywords: Ovarian cancer, VEGF-A, CA-125, Luminex multi-analyte profiling, EIA, FIGO Continuous....

An audit of gynae-oncology practices in ovarian cancer treatment based on enhanced recovery after surgery (ERAS) protocol amongst two gynae-oncology units, in UK and in Pakistan

Abstract Objectives: The goal of this study was to compare the peri-operative practices and complications in ovarian cancer patients undergoing upfront surgery for primary disease at two centers; in UK following ERAS protocol and in Pakistan following traditional practices. Methodology: This was a cross-sectional study based in Gynecology departments of St. Georges Hospital UK, and Aga Khan Hospital Pakistan. The study population consisted of 50 patients from each centre, from January 2015 till December 2016. Results: Demographics were comparable except more prevalent diabetes in Pakistan. Pakistani patients had bowel preparation in 94% as compared to two percent in UK. Duration for nil per mouth was more in traditional approach as well as the use of nasogastric tube and peritoneal drain (0.0001). Epidural anesthesia was used in 78% of patients in Pakistan compared to only 8% in UK. The duration of thromboprophylaxis was also significantly different (UK 28 days versus Pakistan 7 days). Electrolyte imbalances was detected in 80% of Pakistani and 15% of UK patients. Wound infection recorded in 15% of UK and 2% of Pakistani patients. The median length of hospital stay was 7 and 8 days in ERAS and non-ERAS patients respectively. Conclusion: Implementation of ERAS protocol can lead to improvement of postoperative outcomes and good functional recovery without compromising patient safety. Continuous...

Overcoming barriers to cervical cancer screening in a developing country like Pakistan

Cervical cancer is the second most prevalent cancer in Pakistani women of the reproductive age group (15-44 years), while in women of all ages, it ranks as the third most common. It is estimated that around 20 women are found to have cervical cancer per day, ranking Pakistan in the top 10 countries with the highest cancer-related mortality rates. [1] In 2020 alone, cervical cancer took the lives of 341, 831 women, 90% of whom belonged to developing countries including Pakistan. In the same year, it affected 604, 127 women, from which only 12% were from regions like the North America and Europe, while the remaining belonged to the developing world. [2] This startling disparity can be attributed to the introduction of pap smears in the developing world, like the United States and the United Kingdom, which saw >70% decline in cervical cancer mortality since screening through Pap smears was initiated in these countries. [3]. In Pakistan, several studies have shown that women of the reproductive age group lack basic awareness regarding cervical cancer and screening via Pap smears. A survey   on 873 women between 18-28 years found 70.1% of the participants were completely unaware of cancer. [4] A more extensive study consisting of 1070 women between ages 21-30 years found that only 2.2% of their study's population was able to identify the symptoms and risk factors for cervical cancer, while Pap smear was recognized as a screening test by only 2.5% of the same. The Pap smear uptake in this population was 2%. [5]. This lack of knowledge regarding screening can be credited to several factors such as the low educational status of developing countries, little information communicated by the healthcare workers, and the insufficient knowledge of preventive measures amongst them. Other screening barriers include misconceptions about testing guidelines, the socioeconomic status of low-income families, lack of access to testing facilities, personal reluctance due to embarrassment, and family trends of not getting tested due to cultural taboos. [5]. It is crucial to overcome the aforementioned obstacles in order to ensure early screening and treatment of precancerous lesions in women. ---Continue

Fostering the need of HPV Vaccination Programmes in Pakistan

Madam, In Pakistan's female population of 112 million (1) , Human Papillomavirus (HPV) has caused devastating results of cervical cancer in females aged fifteen years and older. Being the second most common cancer in females aged fifteen to forty-four years and third most common cancer amongst females, current statistics estimate 5000 victims and 3000 deaths annually due to HPV. (2)(3). This is becoming a huge burden and needs to be acknowledged. HPV, a circular double-stranded DNA virus, is a common infection of the reproductive tract. Worldwide accepted strategies to reduce the burden of this deadly virus is through vaccines and screening. Due to the uneven distribution of this lethal virus. there are currently three vaccines available that were approved by Food and Drug Administration (FDA) back in 2006, 2009 and 2014, namely Gardasil, Cervarix, and Gardasil-9, respectively(4). CDC has endorsed the need for two doses of the vaccine. At the age of 11-12, The first dose can also be given at 9 years followed by a second dose with an interval of 6-12 months (5). However, in a developing country like Pakistan, HPV vaccination programmes are still a challenge due to lack of awareness amongst the population and inconsistent efforts by the healthcare system in providing the screening and vaccination strategies. Many other factors are related with this gross burden:  the availability of the vaccines, insufficient funds and various collateral factors associated with the spread of rumours through social media. A study recently proved the strength of vaccination at a young age.  It concluded that females’ inoculation at the age of 12 to 13 years significantly reduced the risk of grade 3 cervical intraepithelial neoplasia (CIN) (6). Centres for disease and control and prevention (CDC) has stated that the majority of the people who are unvaccinated and sexually active will get HPV during their lives. Therefore, there is an essential need to vaccinate children below the age of fifteen years so that 33,000 of these cancers can be prevented that are caused by this infection. Since, cervical cancer is a public health problem, a global strategy for its elimination was inaugurated in 2020 by WHO. Despite the worldwide challenges, WHO did not take a step back and continued its challenging efforts. However, situation in Pakistan did not improve. ---Continue

Awareness, screening, Practices and attitudes of cervical cancer among doctors and nursing staff working at a tertiary care center

Objectives: To assess knowledge, attitude and practice of medical and paramedical staff about cervical cancer as well as its screening and prevention. Methods: The descriptive cross-sectional study was conducted at the Jinnah Post-graduate Medical Centre, Karachi, from March 1 to August 30, 2019, and comprised women medical and paramedical staff randomly selected from different specialties. Data was collected using a structured questionnaire. Data was analysed using SPSS 20. Results: Of the 347 participants 144(41.5%) were nurses and 203(58.5%) were doctors. The overall mean age was 26.22±6.38 years. Of the total, 108(30%) respondents were married and 239(68%) were single. Overall, 239(68.8%) were well aware of Pap smear being the screening test; 85(24.5%) were aware of the true guidelines to repeat the test; 152(43.8%) had an idea of the exact use of visual Inspection with acetic acid; 61(17.6%) had got a Pap smear done; and 156(45%) thought they were at risk of developing carcinoma cervix. The common risk factors identified were multiple sexual partners 254(73.2%), age at first sexual intercourse 160(46%), smoking 131(37.8%), foul-smelling discharge 221(63.7%), and post-coital bleeding 231(66.6%). Conclusion: Cervical cancer prevalence is rising due to inadequate knowledge and awareness among healthcare personals. Improvement can be brought by regular use of Pap smear. Key Words: Cervical cancer, Pap smear, Healthcare professionals, Visual inspection with acetic acid.

Determination of ROC Curve based diagnostic strength of miRNA in ovarian cancer

Objective: To examine the diagnostic accuracy of 10 serum-derived micro ribonucleic acids in the early detection of ovarian cancer. Method: The cross-sectional, comparative study was conducted at the Department of Physiology and Cell Biology, University of Health Sciences, Lahore, Pakistan, from February 6, 2018, to August 1, 2021, and comprised women aged 20-70 years diagnosed with ovarian cancer and tentatively planned for surgical procedures. Serum micro ribonucleic acid levels were analysed using quantitative reverse transcription polymerase chain reaction. Data was analysed using SPSS 24, while the micro ribonucleic acid expression profile was analysed using GraphPad Prism. Results: There were 24 women with mean age 44±9.92 years. Cancer antigen 125 had a positive correlation with HSA-miR519d-5p, HSA-miR378-3p, HSA-miR16-5p and HSA-miR21-5p (p<0.05). The diagnostic value of HSA-miR16-5p and HSA-miR21-5p improved from CA125 baseline to CA125 follow-up (6 months after surgery but before chemotherapy), with an area under the curve of 0.56 and 0.82, respectively. The area under the curve for diagnosing cancer stages based on HSA-miR16-5p and HSA-miR21-5p was 0.37 and 0.70, respectively. Conclusion: Cancer-specific micro ribonucleic acids, such as HSA-miR21-5p and HSA-miR16-5p, were found to have diagnostic potential, and could be used in combination with cancer antigen 125 for the screening of ovarian cancer. Key Words: Micro ribonucleic acid, miRNA, Correlation, Expression, Ovarian cancer, CA125.

Impact of delay in interval debulking surgery after neoadjuvant chemotherapy on survival in ovarian cancer

Objective: To determine the impact of delay between neoadjuvant chemotherapy and cytoreductive surgery on progression-free survival and overall survival in ovarian cancer cases. Method: The retrospective study was conducted at the Department of Surgical Oncology, Shaukat Khanum Memorial Cancer Hospital & Research Centre, Lahore, Pakistan, and comprised data from January 2019 to January 2022 of women diagnosed with stage III high-grade serous ovarian cancer who received neoadjuvant chemotherapy and underwent subsequent interval debulking surgery. The patients were divided into groups A and B based on time to surgery within 6 weeks and time to surgery more than 6 weeks, respectively. The endpoint was taken as progression-free survival and overall survival on follow-up. Data was analysed using SPSS 27. Results: Of the 2,100 patients who underwent surgery for ovarian cancer, 118(5.6%) women with mean age 52.18±9.3 years (range: 28-73 years) were included; 53(45%) in group A and 65(55%) in group B. Overall recurrence rate in this cohort was 76(64.4%); 36 (67.9%) in group A and 40 (61.5%) in group B. The mean progression free-survival was 15±1.5 months in group A and 18±2 months in group B (p=0.854). The mean overall survival across the sample was 44±1.8 months, and intergroup difference was not significant. (p=0.336). Conclusion: Delay in interval debulking surgery after neoadjuvant chemotherapy was not found to have a significant impact on progression-free survival and overall survival in ovarian cancer cases.

Prevalence of cervical dysplastic lesions in cervical smears from Baghdad city: a single centre study

Objective: To assess the association of demographic and clinical features of patients with clinicopathological markers in cases of abnormal Pap smear. Method: The retrospective study was conducted from July 2020 to June 2021 at Al-Elwiya Maternity Teaching Hospital, Baghdad, Iraq, and comprised data from January 2019 to June 2020 of women who underwent Pap-smear. Data was retrieved for patients' age, marital status, smoking status, clinical symptoms at presentation, findings of clinical and cytological examinations, as well as follow-up or human papillomavirus testing data where applicable. Data was analysed using SPSS 26. Results: Of the 560 women with mean age 40.42±10.211 years, 26(4.6%) were attending the hospital for routine check-ups/screening, and 12(2.1%) for follow-up screening with previous abnormal Pap-tests, while the rest had been referred for medical consultation. The most common diagnosis was negative for intraepithelial lesion or malignancy 403(72%) Cervical epithelial abnormalities were seen in 136(24.3%) cases, and, of them, 12(8.8%) returned for follow-up. Epithelial abnormalities had a significant association with age, clinical presentation, and clinical examination results (p<0.05), while it had a non-significant relation with marital and smoking statuses (p>0.05). Conclusion: The majority of subjects were referred cases, with routine cervical screening being <5%. Increasing public awareness about the importance of cervical screening and follow-up is essential. Key Words: Papanicolaou, Uterine Cervical, Papillomavirus Viruses, Demography,  Smoking

Evaluation of Pre malignant cervical lesions in females presenting with abnormal pelvic complaints

To evaluate premalignant cervical lesions by using Papanicolaou smears in females presenting with abnormal pelvic complaints. The descriptive cross-sectional study was conducted from June to November 2013 at the Department of Histopathology, Mayo Hospital, Lahore, and comprised female patients aged 25-70 years presenting with abnormal pelvic complaints with no cause in the uterus checked through ultrasonography who were undergoing cervical Papanicolaou smear. The smears were spray-fixed and placed in 95% reagent alcohol and was then stained with haematoxylin and eosin stain. The cytological examination was carried out under light microscope. SPSS 16 was used for data analysis. There were 210 women with a mean age of 39.51±8.32 years. Vaginal discharge was present in 89(42.4%) women; postcoital bleeding in 12(5.7%), and intermenstrual bleeding was present in 21(10%) women. Dyspareunia was present in 33(15.7%) women, and pelvic pain in 60(28.6%). Overall, premalignant cervical cancer was noted in 17(8.1%) patients. Atypical squamous cells of unknown significance was present in 5(2.4%) women, low-grade squamous intraepithelial lesion (LSIL) in 8(3.8%), and high-grade squamous intraepithelial lesion in 4(1.9%) patients of cervical cancer. The frequency of premalignant cervical lesions in symptomatic patients was high enough to highlight the importance of early detection of cervical cancer.

Publisher

Pakistan Medical Association

ISSN

0030-9982