The Indian Journal of Medical Research

Barriers to HPV vaccination among adolescent girls in India: A scoping review

Background & objectives The aim of this scoping review is to systematically map the existing research on human papillomavirus (HPV) vaccination uptake among adolescent girls in India, with a focus on ( i ) identifying the current trends, and ( ii ) examining the challenges and facilitators of vaccine uptake. Methods The review adheres to the scoping review framework developed by Arksey and O'Malley. A thorough search of peer-reviewed literature was carried out utilizing databases such as PubMed, Scopus, and Web of Science. Studies published between 2008 and 2025 were assessed for relevance. The socio-ecological model was used to chart and synthesize data, categorizing barriers and enablers at the individual, interpersonal, community, institutional, and policy levels. Results A total of 37 studies were included. Lack of awareness, sociocultural stigma, economic constraints, and insufficient assistance from the health system were highlighted as some of the main barriers. Government awareness initiatives, healthcare provider recommendations, and school-based interventions were found to facilitate HPV vaccination. Interpretation & conclusions Improving HPV vaccine uptake in India requires addressing multi-level barriers with integrated public health initiatives and policy interventions.

Role of miRNAs, miR-135b-5p & miR-21-5p in metastasis of cervical cancer

Background & objectives Persistent infection with high-risk human papillomaviruses (HPV) is a major cause of cervical cancer, inducing the hypoxic response by stabilising hypoxia inducing factor-1 alpha (HIF-1α). Under normoxia, HIF-1α is regulated by tumour suppressors genes, LIMD1 and VHL . This study aimed to elucidate the functional roles of two microRNAs, miR-135b-5p and miR-21-5p, in regulating LIMD1/ VHL and their impact on various cellular phenotypes relevant to progression of cervical cancer. Methods Expressions of miR-135b-5p, miR-21-5p, LIMD1 , and VHL was assessed using quantitative real-time polymerase chain reaction (qRT-PCR). Target validation was performed via dual-luciferase assays. Functional assays (proliferation, migration, invasion, apoptosis, and cell cycle analysis) were conducted in SiHa cells following individual and combined miRNA inhibition. Results Inhibition of miR-135b-5p and miR-21-5p significantly restored LIMD1 ( P = 0.019) and VHL ( P = 0.025), respectively, leading to reduced HIF-1α expression ( P <0.03). Dual miRNA inhibition had a profound impact on reducing proliferation, migration, invasion and enhancing apoptosis compared to individual knockdowns, whereas G0/G1 arrest was more profound in individual knockdown compared to control cells. Interpretation & conclusions miR-135b-5p and miR-21-5p act synergistically as oncomiRs by suppressing LIMD1 and VHL , promoting HIF-1α-mediated cervical cancer progression. This study demonstrated the synergistic oncogenic role of miR-135b-5p and miR-21-5p in cervical cancer via co-regulation of the LIMD1-VHL-HIF-1α axis.

HPV-DNA testing from self-sampled menstrual blood using M-strip: A proof-of-concept study on feasibility & acceptance of a novel biosampling method

Background & objectives Screening for cervical cancer by self-sampling appears more acceptable to women and has the potential to boost screening uptake, which is dismal at present in India. Studies have shown that menstrual blood (MB) provides equivalent results to cervical smear for Human Papillomavirus (HPV)-Deoxyribonucleic acid (DNA) testing, but sample collection needs standardization. This study explored the feasibility and acceptance of self-sampling using ‘M-strip’ for high-risk HPV DNA (hr-HPV DNA) testing from MB. Methods One hundred and eleven women aged 30-50 yr without a previous diagnosis of pre-cancer or cancer used the M-strip to collect the MB sample. The strip was peeled off the sanitary pad after use, sent in a zip-lock pouch, and tested for high-risk human papillomavirus (hr-HPV) DNA by real-time polymerase chain reaction (rt-PCR). Instructions were provided verbally, in video illustration, and print. Feedback from participants regarding acceptance and comfort in sampling was documented, and from women who refused to participate. Results Seventy-seven women provided MB samples, all of which were evaluable. Six tested positive for hr-HPV DNA, and all six had direct cervical smears obtained subsequently. Randomly selected HPV DNA-negative MB samples were also tested by direct cervical smear. Positive and negative MB samples were 100 per cent in concordance with the findings from direct cervical smears. Participants expressed a high level of acceptance and preference for this method. Interpretation & conclusions Women could successfully collect adequate samples with the M-strip for hr-HPV DNA testing. Using M-strip with their sanitary pads was preferred by and highly acceptable to women in this study.

Polymorphism of interleukin-6 -174 G/C (rs1800795) & the corresponding interleukin-6 level as a prognostic marker of cervical cancer

Background & objectives: Aetiology of cervical cancer (CaCx) is multifactorial. Besides human papillomavirus (HPV) infection, many immunogenetic factors are involved in this complex process. The present study was carried out to investigate one such factor, interleukin-6 (IL-6), a central pro-inflammatory cytokine and a polymorphism at its promoter region -174 G/C (rs1800795) with CaCx. Methods: HPV-infected women with or without CaCx were enrolled in group I and II, respectively. Another group of uninfected healthy women was also included as group III for comparison. Polymorphism in IL-6-174 G/C and IL-6 levels were analyzed by sequence-specific primer PCR (PCR-SSP) and ELISA, respectively. Results: Groups I (n=111) and II (n=87) had significantly higher frequency of IL-6-174 GG genotype [odds ratios (OR)=3.9; P<0.001 and OR=3.2; P<0.001, respectively] as compared to group III (n=163). Furthermore, individuals with GG or GC genotypes had high IL-6 levels than those with CC genotypes. IL-6 levels were significantly (P<0.001) elevated in group I. This was also significantly high in untreated cases as compared to treated (P<0.05) ones. IL-6 levels of treated group were comparable with groups II and III. Interpretation & conclusions: Our results suggested a possible association of IL-6-174 GG with CaCx, which was also associated with high IL-6 levels. Decreased levels of IL-6 following treatment indicate its possible prognostic use in CaCx cases.

High-risk human papillomavirus in Turkish patients with clinically suspicious cervical lesions analyzed by multiplex-PCR

Background & objectives: Human papillomavirus (HPV) infection is known to be the main cause of cervical cancer. This study aimed to determine the prevalence of high-risk HPV genotypes in smear specimens taken from women who had normal or abnormal cytology using a multiplex PCR method. Methods: The study included 270 women aged between 19 and 69 yr with or without suspicious cervical abnormalities. A Pap smear sample from each patient was cytologically examined, and HPV typing was performed using a multiplex fluorescent PCR method. Those who were high-risk HPV positive and had a normal or abnormal cytology were further evaluated by colposcopy and biopsy. Results: The total HPV positivity was 43 per cent (116/270). HPV positivity in the patients with an abnormal cytology was 77 per cent (33/43), whereas it was only 37 per cent (83/227) in women with normal cytology, which showed a significant difference (P<0.05). HPV positivity was also related to the age group when all the subjects were considered (P<0.05), and the highest prevalence of HPV infection was in the 30-39 yr age group. High-risk HPV types 16, 18, 31, 35, 51 and 56 were more common in the normal cytology patients, whereas high-risk HPV types 16, 31, 35, 45, 58 and 68 were commonly found in the abnormal cytology patients. Interpretation & conclusions: The determination of high-risk HPV genotypes in women with clinically suspicious cervical lesions should be conducted during an annual follow-up, irrespective of a normal or abnormal cytology by the age of 30 years or above.

Effect of health education on acceptance of human papilloma virus vaccine among parents of adolescent girls of Bishnupur, Manipur: A quasi-experimental study

Background & objectives India contributes maximum to world’s cervical cancer burden. Prevention through vaccination is one of the pillars of the global strategy adopted by the World Health Organization (WHO) for the elimination of cervical cancer. Uptake of human papillomavirus (HPV) vaccine, which is about to be introduced in Universal Immunization Programme can be predicted by assessing its acceptance. Methods A quasi-experimental study was conducted among parents of adolescent girls of Bishnupur from February to May 2023 to evaluate the effect of a one-on-one health educational intervention programme on acceptance of the HPV vaccine. Data were collected by face-to-face interviews using a structured questionnaire based on the Health Belief Model from 70 participants selected through convenience sampling. Participants who responded ‘definitely yes’ to getting their daughters vaccinated with the HPV vaccine were considered as ‘vaccine acceptant’. Health education comprised three sessions two wk apart. Descriptive statistics, Cochrane’s Q and ANOVA were applied using SPSS 26. Results The median age of the participants was 38 (IQR: 34-44) yr, and 77.1 per cent were females. HPV vaccine acceptance improved significantly over time from 61.4 to 81.4 to 88.6 per cent (P=0.001), respectively. On application of repeated measure ANOVA, perceived benefits of vaccination (P<0.001) and perceived susceptibility to disease (P<0.001) improved significantly across the three time points, whereas perceived severity (P=0.051) and perceived barriers (P=0.367) did not. Interpretation & conclusions Health education intervention was effective at improving vaccine acceptance. Awareness programmes before the rollout of HPV vaccination and continuous re-enforcement would improve parents’ perceived benefits and thereby potentially increase vaccine coverage.

ALDH1 & CD133 in invasive cervical carcinoma & their association with the outcome of chemoradiation therapy

Background & objectives: Chemoradiation is the standard therapy for locally advanced invasive cervical cancer and response to treatment determines the outcome. Cancer stem cells (CSCs) and epithelial–mesenchymal transition (EMT) play a role in response to treatment and hence the aim of this study was to evaluate if their levels in pre-treatment biopsies by immunohistochemistry (IHC) could predict response to treatment and outcome. Methods: The study comprised 60 patients with FIGO Stage IIB/III invasive cervical carcinoma treated by chemoradiation. They were divided into two groups based on their clinical outcome: group 1, 30 patients who had no evidence of disease at 48 month follow up and group 2, 30 patients who had disease relapse within 6-12 months of treatment completion. IHC was performed for CSC markers (ALDH1, CD133, Nanog and Oct-4), EMT markers (E-cadherin and vimentin) and squamocolumnar junction (KRT7) markers and H-scores determined. Intergroup comparison was performed. The expression of these markers was also evaluated in histological sections of cervical pre-cancer (CIN1 and CIN3) in comparison to normal cervix. Results: Cervical Intraepithelial Neoplasia grade 3 (CIN3) showed high expression of ALDH1 and KRT7 as compared to normal cervical epithelium. Aldehyde dehydrogenase 1 (ALDH1) and CD133 were overexpressed in 70 and 24 per cent cervical carcinoma cases whereas E-cadherin showed reduced expression in invasive carcinoma as compared to normal controls. ALDH1 overexpression was significantly associated with disease relapse in invasive cervical carcinoma treated by chemoradiation (P<0.01). Interpretation & conclusions: Determination of ALDH1 levels in pre-treatment cervical biopsies of invasive cervical carcinoma may be useful for prediction of response to chemoradiation, with high levels predicting for a poor response.

Practical aspects of palliative care & palliative radiotherapy in incurable cervical cancer

Cervical cancer is the most common cause of cancer-related deaths among economically disadvantaged women. The symptoms of pain, discharge, constipation, foul smell, insomnia and depression can be controlled with inexpensive medicines such as oral morphine, maintenance oral metronidazole, antidepressants and laxatives. These medications should be prescribed according to the palliative care guidelines and titrated to the individual patient’s clinical response, pathophysiology, and metabolic parameters. A hypothetical clinical scenario illustrates some aspects of pain and symptom management, inter-disciplinary palliative care, medical ethics and communication needs in low-resource settings. Palliative radiotherapy is a cost-effective intervention to reduce vaginal discharge, bleeding, pressure effects and nociceptive or neuropathic pain caused by pelvic and para-aortic disease. The role of palliative radiotherapy in patients with malignant fistulae is discussed and the literature on hypo-fractionated pelvic radiotherapy is briefly reviewed.

Defining the role of high-dose radiation in oligometastatic & oligorecurrent cervical cancer

Around 5-8 per cent of women diagnosed with cervical cancer present with metastatic disease at presentation and 16-25 per cent of patients fail at either within irradiated fields or at distant sites post-curative therapy in advanced cervical cancers. Conventionally, chemotherapy with palliative intent constituted the mainstay of treatment with modest survival outcomes and radiation therapy was reserved for symptomatic benefit only. While targeted therapies and immunotherapy have been added in therapeutic armamentarium, the impact on the outcomes is modest. In limited metastatic disease, radiation therapy to metastatic sites from different primary cancers has shown survival benefits; however, the data are scarce in cervical cancer. With a better understanding of the molecular biology of the metastases and recurrence pattern, emphasis is laid upon total eradication of the disease rather than offering relief from symptoms. This article summarizes the role of radiation therapy in limited metastatic disease and recurrent cervical cancer.

Contribution of Tata Memorial Centre, India, to cervical cancer care

Cervical cancer continues to be a major public health concern in India and other low- and middle-income countries. Tata Memorial Centre, India, has been at the forefront in providing treatment, developing best practice guidelines for low-cost efficacious interventions, conducting practice-changing randomized trials and engaging in regional and international collaborations for education and research in cervical cancer. This review summarizes how cervical cancer research and clinical care has evolved over the past two decades at the Tata Memorial Centre, right from testing low-cost public health screening of cervical cancers to the incorporation of the latest technological advancements and providing high-quality evidence for therapeutic management of cervical cancer. The various ongoing strategies for improving survival, toxicity reduction, translational research studies, educational activities and teaching programmes initiated by the Tata Memorial Centre at both national and international levels are discussed.

Radiological evaluation of metastatic lymph nodes in carcinoma cervix with emphasis on their infiltrative pattern

Background & objectives: Imaging has been added to the International Federation of Gynecology and Obstetrics (FIGO) 2018 staging system of cervical carcinoma. This study was performed to assess the impact of imaging in staging and to ascertain the prevalence and pattern of nodal metastasis on contrast-enhanced computed tomography (CECT) in patients with cervical carcinoma who were treated based on FIGO 2009 staging system. Methods: This retrospective study was conducted to evaluate all patients with biopsy-proven cervical carcinoma who underwent CECT of abdomen at a tertiary cancer centre in north India from April 2017 to April 2019 and for whom either baseline or follow up scans were available. In patients with enlarged or necrotic lymph nodes, the location, size and pattern of infiltration of adjacent organs were recorded. Results: A total of 602 patients of cervical carcinoma had undergone CT during the study period, of whom 138 (22.9%) underwent CT at baseline and 464 (77.1%) patients during follow up. The FIGO (2009) stage distribution at the time of presentation was stage IB: 109 (18.1%); stage IIA: 14 (2.3%), stage IIB: 118 (19.6%), stage IIIA: 12 (2%), stage IIIB: 277 (46%), stage IVA: 20 (3.3%) and stage IVB: 52 (8.6%). Ninety of the 138 (65.22%) patients underwent a stage shift according to the FIGO 2018 because of the presence of enlarged lymph nodes at baseline scan. Sixteen (2.7%) patients had infiltrative nodal masses most commonly involving the blood vessels (n=14) followed by ureter (n=8), bones (n=5), muscle and bowel (n=3, each). The majority (14/16) of these patients presented with vague abdominal pain, discomfort and vomiting, while two had bone pain. Interpretation & conclusions: CECT at baseline helps in accurately assessing the stage in cervical carcinoma. It helps in the identification of lymph node metastasis in cervical carcinoma, which is crucial for guiding accurate management.

Endometrial serous carcinoma: A retrospective review of histological features & their clinicopathological association with disease-free survival & overall survival

Background & objectives: Endometrial serous carcinoma (ESC) is a high-grade epithelial neoplasm with increased risk for metastasis and recurrence. This study was aimed to assess various histomorphological features of ESC and their clinicopathological association with disease-free survival (DFS) and overall survival (OS). Methods: A total of 205 slides (belonging to 120 patients) diagnosed as ESC from January 2009 to December 2015 were reviewed. Receiver operating characteristics (ROC) curves were established for the diagnostic performance of depth of invasion (DOI), tumour-free distance (TFD) to serosa and percentage myometrial invasion (MI%). OS and DFS were generated by Kaplan-Meier curves and prognostic significance by Cox regression analysis. Results: The mean age at diagnosis was 61.8 yr and the mean tumour size was 4.01 cm. Majority of the females were multiparous (84%; n=94) and postmenopausal (89.2%; n=107). On histopathology, <50 per cent of MI was identified in 37 of the 104 (35%), while 62/104 (59.61%) patients had ≥50 per cent MI. Seven (6.7%) patients had full-thickness invasion with serosal involvement, while five (4.8%) patients had no microscopic MI (minimal uterine serous carcinoma). Information about MI was not available in 16 patients. TFD ≥7.0 mm, DOI ≥6.0 mm and MI% ≥40 were significant variables in univariate analyses for OS; however, on multivariate analysis; none of these turned out to be an independent predictor in terms of OS. For DFS, DOI (≥6.0 mm) and MI% (≥40%) showed a significant association, in univariate as well as multivariate analysis; however, TFD (≤7.0 mm) did not show any significant association with DFS. Follow up data were available in 111 of the 120 (92.5%) patients with a five-year OS and DFS of 22.2 and 17.2 per cent, respectively. Interpretation & conclusions: Conventionally calculated DOI (less than or more than half thickness) did not show significance in the present study. Thus, calculating the actual myometrial DOI, MI% and TFD to serosa have the potential for contributing meaningfully to prognostication of ESC.

Role of serum microRNAs as biomarkers for endometriosis, endometrioid carcinoma of ovary & endometrioid endometrial cancer

Background & objectives: Accurate and early diagnosis is imperial in the management of endometriosis, endometrioid carcinoma of ovary (ECO) and endometrioid endometrial cancer (EC), yet there are no definitive diagnostic methods available for these diseases. Therefore, the present study was aimed to evaluate the diagnostic potential of differentially expressed miRNAs in serum samples of women with endometriosis, ECO and EC to establish them as diagnostic biomarkers. Methods: Blood samples (5 ml) were obtained from 40 patients (n=10/study group) undergoing laparoscopy/laparotomy/hysterectomy. miRNA-rich RNA was extracted from the serum samples, and quantitative real-time (qRT)-PCR was performed to check the expression levels of miR-16, miR-99b, miR-20a, miR-145, miR-143 and miR-125a in all the samples. Receiver operating characteristic (ROC) curve analysis was done to check the diagnostic potential. Results: In endometriosis, miR-16 was downregulated (P<0.05) whereas miR-99b, miR-125a, miR-143 and miR-145 were upregulated (P<0.05). In ECO group, downregulated expression of miR-16 and miR-125a (P<0.05) was observed, whereas miR-99b, miR-143 and miR-145 were upregulated (P<0.05). In endometrioid EC, miR-16, miR-99b, miR-125 and miR-145 were downregulated (P<0.05), whereas miR-143 was upregulated (P<0.05). ROC curve analysis showed that, for endometriosis, miR-99b, miR-125a, miR-143 and miR-145 served as diagnostic markers. miR-145 showed diagnostic power for ECO, and for endometrioid EC, miR-16, miR-99b, miR-125a and miR-145 showed diagnostic potential. Interpretation & conclusions: The present findings suggested that certain circulating miRNAs (miB99b, miR-16, miR-125a, miR-145) might act as indicators and discriminators of endometriosis and endometrioid subtypes of EC and ovarian cancer and might serve as potential biomarkers for early diagnosis and management of these debilitating diseases.

Evaluating different samples & techniques for hr-HPV DNA genotyping to improve the efficiency of risk profiling for oral & cervical cancers in Sikkim, India

Background & objectives Oral and genital HPV infection in men may be a source of cervical diseases in their women partners as well as disease in themselves. This study aimed to evaluate and compare the performance of Hybrid Capture 2 (HC2) in physician-collected cervical samples and qPCR in self-collected urine and oral gargle samples of women and men, respectively, for hr-HPV infection status and genotyping. Methods One thousand and two hundred biological samples were collected from 200 women (urine, oral gargle, and cervical smear) and 200 men (urine and oral gargle) visiting a referral hospital in the remote Himalayan State of Sikkim. The extracted genomic DNA from urine and gargle samples were profiled for hr-HPV genotypes using quantitative polymerase chain reaction (qPCR) and HC2 for cervical samples. Results In women, hr-HPV was detected in 17.5 per cent of cervical samples by HC2, 25.5 per cent of urine, and 7 per cent of gargle samples by qPCR. For men, hr-HPV was detected in 8 per cent urine and 5 per cent gargle samples by qPCR. Among the HPV-positive women, 56 per cent of urine samples and 20 per cent of oral samples showed single-genotype infection, while the remaining had multiple genotypes. Amongst the HPV-positive men, 62.7 per cent of urine samples and 85.7 per cent of oral samples showed single-genotype infection while the remaining had multiple genotypes. Compared to Pap, the area under ROC was good for HC2 (AUC=0.89) and for qPCR (AUC= 0.852). Interpretation & conclusions HC2 for cervical and qPCR-based HPV DNA assay for urine and gargle sample is suitable for risk profiling for cervical cancer (CC) and oral cancer (OC) screening programmes.

Cascade of care for people with positive symptoms of common cancers in selected primary health centres of Puducherry: An explanatory mixed-method study

Background & objectives Cancer is a leading cause of death worldwide and constitutes a public health priority. Delays in diagnosis and treatment of cancer can adversely impact survival, recovery, and cost of treatment. The objective of this study was to estimate the proportion seeking timely care among those having early warning signals for oral, breast or cervical cancer and to explore the facilitators and barriers to early detection. Methods The study was conducted among 241 participants, including those having early signals for selected cancers and women who underwent opportunistic cervical cancer screening in the selected health facilities. Information regarding symptom appearance, presentation to any registered medical practitioner, confirmatory diagnosis, and treatment initiation were obtained from medical records. In-depth Interviews (IDIs) were conducted among six participants to explore facilitators and barriers to cancer detection. Results Among 7300 people screened using the Community Based Assessment Checklist (CBAC), 128 (1.7%) had warning signals for any one of the cancers. The percentage of people who sought medical care for oral, breast and cervical cancer symptoms were 80 per cent, 82 per cent and 57 per cent, respectively. Among those who underwent opportunistic cervical cancer screening in health centres (113), the screen positivity rate was 11 per cent, and adherence to referral for confirmation was 80 per cent. The median pre-diagnostic and diagnostic delays for the three cancers were 79 [Interquartile range (IQR): 44-126] and 27 (IQR: 13-73) days. One individual was diagnosed with oral cancer, and the treatment delay was 27 days. Facilitators identified for early seeking of care were encouragement by family and low-cost treatment at public facilities. Major barriers identified were neglect of symptoms by participants and their responsibilities towards family. Interpretation & conclusions Although very few people were identified to have early warning symptoms using CBAC, a substantial proportion of them sought medical care and underwent confirmatory diagnosis. Screen positivity rate and treatment-seeking behaviour were better among women undergoing opportunistic cervical cancer screening in the health centres. Measures need to be taken to improve health literacy among people to reduce diagnostic delay for cancers.

Molecular epidemiology of human papillomavirus variants in cervical cancer in India

Background & objectives Cervical cancer (CC) has been documented as the fourth most common cancer worldwide. Persistent infections with high-risk human papillomavirus (hr-HPV) have been suggested in the development of CC. Although prophylactic vaccines are available for the prevention of prevalent hr-HPV types, intra-type variations exist within a particular HPV type that has varying oncogenic potential as well as the mechanism of pathogenicity and varying neutralization by antibodies. Therefore, we carried out a systematic review to determine the distribution of HPV intra-typic variations in different geographical locations of India and their reported implications. Methods Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines were followed to retrieve relevant articles from the standard databases using appropriate keywords. Consequently, 17 articles were included in the current review after screening based on inclusion and exclusion criteria. Results The majority of articles included in this review reported variations within the HPV16 E6 gene, followed by the L1 and E7 genes. Analysis of available data indicated the differential regional distribution of some variations. These variations have also been reported to impact the biological functions of various viral proteins. Interpretation & conclusions The distribution of lineages varied with the different genomic regions sequenced. Additionally, there were certain unique and common variations in the HPV genome with respect to geographical regions. Hence, we suggest the identification of region-specific variations for the development of diagnostic and prognostic interventions.

Point-of-care tests for human papillomavirus detection in uterine cervical samples: A review of advances in resource-constrained settings

Incidence of cervical cancer and associated mortality are still high in resource-constrained countries due to the lack of infrastructural facilities and trained workforce. Human papillomavirus (HPV)-based screening tests offer a better sensitivity (>90%) for the detection of cervical high-grade lesions. However, these tests usually require an extensive laboratory set-up and trained technical staff. Moreover, the high cost of the currently available and approved HPV tests precludes their use in the cervical cancer screening programmes in resource-limited settings. Hence, there is a felt need for a low-cost point-of-care (POC) HPV test with good performance characteristics to help augment cervical cancer screening in such settings. A recent meta-analysis demonstrated a good sensitivity and specificity for two of the commercially available POC HPV tests. The present review discusses the merits and limitations of the current commercially available POC and near-POC devices for HPV-based cervical cancer screening. The technologies that have the potential to be developed into low-cost POC tests and newer promising modalities for HPV-based POC or near POC have also been highlighted. This review underscores the need for collaborative and coordinated research for development of POC or near-POC HPV-based tests to be used in cervical cancer screening. Efforts need to be focussed on technologies that offer ease of performance without the requirement of sophisticated equipment or extensive sample pre-processing coupled with a good sensitivity and cost-effectiveness.

Challenges and opportunities to making Indian women cervical cancer free

Comparison of acceptability & efficacy of thermal ablation (thermocoagulation) & cryotherapy in VIA positive cervical lesions: A pilot study

Background & objectives: The World Health Organization (WHO) has endorsed thermal ablation (thermocoagulation) as an efficient and safe modality for treatment of cervical pre-cancer lesions. More evidence is being looked up by WHO through rigorous studies for health delivery models using screen-and-treat strategies incorporating thermal ablation and studies comparing it against the conventional standard modality cryotherapy. The objective of this study was to assess the acceptability of thermal ablation both among the providers and clients and compare the same with cryotherapy. Methods: A randomized control trial was conducted for one year from September 2019 to October 2020 after obtaining ethics approval. Computer-generated random number table was used for randomization, and eligible candidates were divided into two groups following informed consent. Women with visual inspection with acetic acid (VIA) positive cervical lesions in Group A received cryotherapy and Group B received thermal ablation. After the procedure, the acceptability of the provider and the client were assessed using the International Agency for Research on Cancer-validated questionnaire for both the procedures. Immediate side effects and problems at six weeks and at six months were assessed as well. Efficacy was decided by the absence of VIA positivity at six months. Results: The overall VIA positivity in this study was 11.8 per cent. Thermal ablation (thermocoagulation) had better provision and client acceptability than cryotherapy (significant difference). The efficacy of thermal ablation was 97.6 per cent, while, it was 92 per cent for cryotherapy (not significant). Interpretation & conclusions: In the context of screen-and-treat programme in settings such as India, thermal ablation appears to be a better method of treatment than cryotherapy for cervical pre-cancerous lesions particularly in terms of better provision and client acceptability.

Implications of the revised cervical cancer FIGO staging system

The 2018 revised International Federation of Gynaecology and Obstetrics (FIGO) staging of cervical cancer has brought about a paradigm shift by offering the option of adding imaging and pathology to clinical staging. This makes it applicable to all types of resource situations across geographies with implications for all stakeholders, including gynaecologists, gynaecologic oncologists, radiologists, pathologists and radiation and medical oncologists. The new staging classification has more granularity, with three sub-stages of stage IB and a new category of stage IIIC for all cases with lymph node (LN) involvement. The major limitations of clinical staging were inaccurate assessment of tumour size and inability to assess pelvic and para-aortic LNs with the limited investigations permitted by FIGO to change the stage. This resulted in understaging of stages IB-III, and overstaging of stage IIIB, which has been largely overcome by incorporating imaging findings. Although any imaging modality can be used, magnetic resonance imaging appears to be the best imaging modality for early-stage disease owing to its better soft-tissue resolution. However, the use of contrast-enhanced computed tomography or ultrasonography are also feasible options, depending on the availability and resources. But wherever pathological evaluation is possible, it supersedes clinical and radiological findings.

Para-aortic lymph node involvement in cervical cancer

Locally advanced cervical cancer with the involvement of para-aortic lymph nodes (PALN) is a common occurrence in low-income and low-middle-income countries. With the incorporation of PALN in the recent FIGO staging, therapeutic management becomes crucial. There are varied presentations of this group which may range from microscopic involvement to extensive lymphadenopathy. Various imaging modalities have been studied to accurately diagnose PALN metastases without surgical intervention, while some investigators have studied the survival benefit of para-aortic lymph node dissection for accurate staging and guiding extent of radiation. With recent advances in radiation therapy, its application to treat bulky nodal metastases and the role of prophylactic irradiation have been reported. In this review, the available evidence and the scope of further interventions is presented.

Updates on systemic therapy for cervical cancer

Cervical cancer is one of the most common cancers in the world both in terms of incidence and mortality, more so important in low- and middle-income countries. Surgery and radiotherapy remain the backbone of treatment for non-metastatic cervical cancer, with significant improvement in survival provided by addition of chemotherapy to radiotherapy. Survival as well as quality of life is improved by chemotherapy in metastatic disease. Platinum-based chemotherapy with/without bevacizumab is the mainstay of treatment for metastatic disease and has shown improvement in survival. The right combinations and sequence of treatment modalities and medicines are still evolving. Data regarding the molecular and genomic biology of cervical cancer have revealed multiple potential targets for treatment, and several new agents are presently under evaluation including targeted therapies, immunotherapies and vaccines. This review discusses briefly the current standards, newer updates as well as future prospective approaches in systemic therapies for cervical cancer.

Anti-angiogenic therapy in ovarian cancer: current situation & prospects

Ovarian cancer (OC) is one of five leading causes of cancer related death among women worldwide. Although treatment has been improving, the survival rate has barely improved over the past 30 years. The fatality rate is due to asymptomatic early signs and the lack of long-term effective treatment strategies for advanced disease. Angiogenesis is an important process in tumour growth and metastasis and is the creation of new blood vessels from existing blood vessels. It is a dynamic and complex process involving various molecular regulatory pathways and multiple mechanisms. The inhibition of angiogenesis has become a recognized therapeutic strategy for many solid tumours. While benefits in progression-free survival have been observed, the OS is far from satisfactory for OC patients who receive antiangiogenic therapy. In this article, the present research status of angiogenesis in OC was reviewed and the reasons for poor antiangiogenic therapeutic effects was explored with the aim to identify potential therapeutic targets that may improve the effect of antiangiogenic therapies.

Risk of gynaecologic cancers in women with metabolic syndrome: A systematic review & meta-analysis

Background & objectives Metabolic syndrome may be associated with the risk of gynaecological cancers. This systematic review aims to evaluate the risk of gynaecological cancers among women with metabolic syndrome. Methods Studies published in English using a search strategy across PubMed, Google Scholar, and Scopus were identified from the earliest available indexing of the respective databases up to September 12-14, 2023. After removing duplicates and conducting a detailed screening by two independent reviewers, 25 studies were identified. Critical appraisal was conducted using JBI checklists for case-control and cohort studies and AXIS checklist for cross-sectional studies. Data extraction was conducted for information pertaining to study design, participant demographics, definition of metabolic syndrome, reported summary measures and type of gynaecological cancer. Results Random effects models were employed separately for each study design, reported summary measures and the type of gynaecological cancers. In case-control, cross-sectional, and cohort studies, presence of metabolic syndrome was associated with uterine/endometrial cancer [odds ratio (OR) 1.99, P<0.01, OR 2.64, P<0.01, hazard ratio (HR) 1.45, P=0.04], respectively. Case-control and cohort studies in ovarian cancer suggested association (OR 3.44, P<0.01, OR 1.02, P=0.79, and HR 1.02, P=0.80). Cohort studies in cervical cancer patients, yielded HR 1.26, P=0.96 and adjusted HR 1.27, P=0.83. The critical appraisal of the included studies was high. GRADE reported low-quality evidence for cervical, uterine/endometrial, and ovarian cancer. Interpretation & conclusions Women with metabolic syndrome are associated with increased risk of gynaecological cancers regardless of study design, type of gynaecological cancer and definitions of metabolic syndrome.

Awareness about the symptoms & risk factors of ovarian cancer among women in North Urban Bengaluru: A cross-sectional study

Background & objectives In low or medium Human Development Index (HDI) nations, late-stage ovarian cancer diagnosis in 75 per cent of women is known to hinder treatment outcomes. However, knowledge and awareness can significantly impact disease progression and outcomes. This study was conducted to determine ovarian cancer awareness, risk factors, and symptoms among women in a community-based setting. Methods This study was conducted in Yelahanka, North Urban Bengaluru, between October 2023 and July 2024. A validated questionnaire, Ovarian Cancer Awareness Measure (OCAM), was used to interview the women. Household data were collected through systematic sampling using the Epicollect-5 mobile application and analysed with Jamovi software version 2.3.28. Results A total of 375 women were interviewed during the study, of which 28.5 per cent were aware of ovarian cancer. With median scores of 4 out of 10 for symptoms and 5 out of 12 for risk factors, there was a general lack of awareness of symptoms and risk factors. Commonly identified symptoms included extreme fatigue (61.7%), pelvic pain (54.2%), abdominal enlargement (51.4%), and back pain (43.9%). The socioeconomic class was significantly associated with symptom awareness (P<0.05). On identifying risk factors of ovarian cancer, the most recognised were a history of ovarian cysts (71%), smoking (64.48%), age >50 yr (55.54%), and being overweight (47.6%). Age, marital status, education, and socioeconomic class (P<0.05) influenced awareness of risk factors. Interpretation & conclusions This study found low ovarian cancer awareness among women in North Urban Bengaluru, emphasising the necessity for focused awareness programmes to enhance early diagnosis and improve health outcomes.

Implication of microRNA-regulated PTEN expression in the clinico-pathology & survival outcomes in advanced ovarian cancer

Background & objectives Phosphatase and TENs in homolog (PTEN), deleted on chromosome 10, plays a salient role in suppressing the proliferative phosphatidylinositol 3-kinase/protein kinase B(PI3K/AKT) signal in cancers. Growing evidence suggests that PTEN is downregulated by microRNAs (miRs) in aggressive cancers, which antagonise its tumour-suppressive activity. This study elucidates the effect of miR-214, miR-433, miR-100, and miR-152 on PTEN expression with important clinical parameters in individuals with Stage III-IV ovarian cancer (OC). Methods This prospective observational study enrolled 104 individuals with OC from January 2018 to December 2020. Demographic and clinical data were collected at presentation and follow up. Tissue samples were analysed using immunohistochemistry, Western blot, and quantitative real time PCR (qPCR)s. Statistical analyses included t-tests, chi-square, correlation coefficient, log-rank, Cox regression, and ROC analysis to assess clinical and survival outcomes. Results The included study participants with OC (mean age 49.29±9.68 yr) presented with advanced stages (96.6%) and had high-grade serous histological subtype (48.5%). Loss of PTEN expression was detected among 50.96 per cent, indicative of poor survival (HR>1; P=<0.05). MiR-214 (P=<0.001) and miR-433 (P=<0.001) were negatively associated, while miR-100 (P<0.001) and miR-152 (P=<0.001) were positively correlated with PTEN mRNA and protein, with miR-214, and miR-152 being independent risk factors to survival of OC patients (HR=>1). The sensitivity and specificity of PTEN and miRs range between 62.5-97 per cent, with diagnostic accuracy (P=<0.001). Interpretation & conclusions The degree of miR-214, miR-433, miR-100, and miR-152 exhibited dysregulation in OC (P=<0.001). The findings of this study suggest that miR-214 and miR-433 can downregulate PTEN whereas miR-100 and miR-152 may have a tumour suppressive role like PTEN. Thus, the signature miR network has the potential to become a diagnostic and prognostic biomarker.

Advances in management of locally advanced cervical cancer

Globally, cervical cancer has the fourth highest cancer incidence and mortality in women. Cervical cancer is unique because it has effective prevention, screening, and treatment options. This review discusses the current cervical cancer advances with a focus on locally advanced cervical cancer. Topics discussed include diagnostic imaging principles, surgical management with adjuvant therapy and definitive concurrent chemoradiotherapy. Emphasis is given on current advances and future research directions in radiation therapy (RT) with an emphasis on three-dimensional brachytherapy, intensity-modulated RT, image-guided RT, proton RT and hyperthermia.

Temporal course of late rectal toxicity & impact of intervention in patients undergoing radiation for cervical cancer

Background & objectives: There is limited information available on the temporal course of late stage radiotherapy adverse effects. The present study reports on the temporal course of late toxicities after chemoradiation and brachytherapy. Methods: Women with cervical cancer who presented with late toxicity after (chemo) radiation were included in the study. Grade of toxicity (Clinical Toxicity Criteria for Adverse Events version 4.03) and type of intervention were recorded at three-monthly interval for the first year and then six monthly until 24 months. Direct cost for the management of toxicity was calculated. Univariate analysis was performed to understand the impact of various factors on persistence of toxicity. Results: Ninety two patients were included in this study. Grades I, II, III and IV toxicities were observed in 50 (54%), 33 (36%), 7 (8%) and 2 (2%) patients, respectively, at first reporting. Patients spent a median of 12 (3-27) months with toxicity. At 12 months, 48/92 (52.2%) patients had a complete resolution of toxicity, whereas 27/92 (29.3%) patients had low grade (I-II) persistent toxicity. Only 6/92 (6.5%) patients who had grade III−IV toxicity had resolution to a lower grade. Four (4.3%) patients died due to toxicity. At 24 months, 9 (10%) patients continued to have grade ≥ III toxicity. On an average, 7 (2-24) interventions were required for the clinical management of late toxicity and median direct cost incurred was JOURNAL/ijmer/04.03/02223309-202108000-00023/math_23MM1/v/2022-09-30T185846Z/r/image-tiff 50,625 (1,125-303,750). Interpretation & conclusions: In this study late radiation toxicity resolved within 12 months in more than half of patients. However, others are likely to have had persistent lower grade toxicity or progression to higher grade. Structured strategies are hence needed for the effective management of late toxicities.

Surgery for cervical cancer

Surgery plays an important role in the management of early-stage cervical cancer. Type III radical hysterectomy with bilateral pelvic lymph node dissection using open route is the standard surgical procedure. There is level I evidence against the use of laparoscopic/robotic approach for radical hysterectomy for cervical cancer. Emerging data support the use of sentinel lymph node biopsy and nerve sparing radical hysterectomy in carefully selected patients with early-stage disease. In locally advanced cervical cancer patients, the use of neoadjuvant chemotherapy (NACT) followed by radical surgery yields inferior disease-free survival compared to definitive concurrent chemoradiation therapy. Therefore, definitive concurrent chemoradiation is the standard treatment for locally advanced disease. Fertility preserving surgery is feasible in highly selected young patients. Role of less-radical surgical procedures in patients’ with low-stage disease with good prognostic factors is under evaluation.

Screening for cervical cancer

Cervical cancer is the fourth most common cancer in women in the world. To eliminate cervical cancer by 2030, the World Health Organization has given the target of 70 per cent coverage of twice lifetime screening. A multitude of screening methods are available, including cytology, human papillomavirus (HPV) DNA testing and visual inspection tests. Precision tests, including molecular and protein biomarkers such as DNA methylation, p16 immunostaining, and HPV mRNA testing help to enhance specificity of the screening. Worldwide HPV DNA testing with or without cytology is used as a screening method of choice, while in resource-poor settings, visual inspection tests are recommended. The major hurdle is a uniform and systematic implementation with a recall method in the population. Besides, controversies still exist regarding strategies to manage HPV-positive women and developing guidelines to screen the vaccinated population.