Invasive Cervical Cancer Research Articles

Clearance of high-risk HPV after large loop excision of the transformation zone of early-stage invasive cervical cancer or adenocarcinoma in situ is highly correlated with the absence of residual cancer

Clearance of high-risk HPV after large loop excision of the transformation zone of early-stage invasive cervical cancer or adenocarcinoma in situ is highly correlated with the absence of residual cancer

Post-marketing study design to evaluate the effectiveness of the 9-valent and 4-valent HPV vaccines on serious HPV-related cervical disease in China.

The 4-valent (4 v) and 9-valent (9 v) human papillomavirus (HPV) vaccines are approved in China for females aged 9-45 years. However, the real-world impact of 4vHPV or 9vHPV vaccination for the prevention of high-grade cervical disease in Chinese women is lacking. Two post-marketing surveillance studies will be conducted to measure the occurrence of high-grade cervical lesions in Chinese women who had received ≥1 dose of the 4vHPV (aged 20-45 years) or 9vHPV (aged 16-26 years) vaccine in Ningbo, China. Vaccination data will be extracted from the Ningbo Regional Health Information Platform (NRHIP) from the date of the first 4vHPV (January 9, 2018) or the first 9vHPV (January 25, 2019) vaccination to March 31, 2021. The primary 4vHPV and 9vHPV vaccinated cohorts will include women vaccinated per protocol. The 4vHPV/9vHPV vaccinated test-negative (cervical HPV negative; ThinPrep cytology test negative) and corresponding matched unvaccinated HPV test-negative sub-cohorts will also be assessed. Outcomes will be the occurrence of new-onset cervical intraepithelial neoplasia grade 2/3, adenocarcinoma in situ, and invasive cervical cancer. This study aims to demonstrate that such a methodological approach is feasible and can be used to assess the impact of HPV vaccination in other regions across China.

Germline variants of homology-directed repair or mismatch repair genes in cervical cancer.

While cervical cancer is associated with a persistent human papillomavirus (HPV) infection, the progression to cancer is influenced by genomic risk factors that have remained largely obscure. Pathogenic variants in genes of the homology-directed repair (HDR) or mismatch repair (MMR) are known to predispose to diverse tumour entities including breast and ovarian cancer (HDR) or colon and endometrial cancer (MMR). We here investigate the spectrum of HDR and MMR germline variants in cervical cancer, with particular focus on the HPV status and histological subgroups. We performed targeted next-generation sequencing for 5 MMR genes and 12 HDR genes on 728 German patients with cervical dysplasia or invasive cancer. In total, 4% of our patients carried a pathogenic germline variant, based on ClinVar classifications and additional ESM1b and AlphaMissense predictions. These included 15 patients with truncating variants in HDR genes (BARD1, BRCA1, BRCA2, BRIP1, FANCM, RAD51D and SLX4). MMR-related gene variants were less prevalent and mainly of the missense type. While MMR-related gene variants tended to associate with adenocarcinomas, HDR gene variants were commonly observed in squamous cancers. While one patient with HPV-negative cancer carried a pathogenic MMR gene variant (in MSH6), the HDR germline variants were found in patients with HPV-positive cancers and tended to associate with HPV18. Taken together, our study supports a potentially risk-modifying role of MMR and HDR germline variants in cervical cancer but no association with HPV-negative status. These variants may be exploitable in future therapeutic managements.

The utility of an HPV genotype assay for cancer screening in self-collected urine/vaginal samples from Japanese women.

Objectives The high incidence of invasive cervical cancer among those who have not undergone cancer screening is a serious problem. This study aimed to investigate the utility of HPV test results from self-collected urine and vaginal samples as screening tools. Design The study was conducted in two steps. First, the appropriate storage container, temperature, and time until urine HPV assay performance were verified. Second, the results of spot urine testing under those conditions and of gynecologist-collected cervical and self-collected vaginal samples were compared to verify the feasibility of using the BD Onclarity® HPV assay for individuals with abnormal cervical cytology. Participants/Materials, Setting, Methods The participants were 121 women with abnormal cervical cytology. Self-collected urine and vaginal samples, along with gynecologist-collected cervical samples, were tested for HPV using the BD Onclarity® HPV assay. The optimal conditions for urine sample storage were identified by comparing the HPV detection rates under various conditions. Results Urine stored in a BD Probe Tec™ (QxUPT) for less than 72 hours at room temperature was found to have the highest HPV positivity rate. Under these conditions, the detection rates of HPV in urine, cervical, and vaginal samples were examined. HPV type 16 was detected in 41.7% of the cervical samples, type 18 in 10%, and types 31 and 52 in 12.6% each. The concordance rate for HPV testing between clinician-collected cervical and urine samples was 63.9% (kappa 0.34; 95% CI: 0.21-0.47), and that between clinician-collected cervical and self-collected vaginal samples was 77.8% (kappa 0.68; 95% CI: 0.53-0.83), indicating good concordance. In a population with an HPV-related lesion/tumor prevalence of approximately 70%, the sensitivity of HPV testing was 82.7% for the cervix, 46.4% for urine, and 75.7% for vaginal samples. Limitations The primary limitation is the lower detection rate of HPV in spot urine samples than in other sample types, indicating room for methodological improvement. The study's findings are based on a specific population, which may limit generalizability. Conclusions We investigated the optimal self-collected urine-to-testing time and temperature. Self-collected vaginal and urine HPV tests show moderate-high concordance with clinician-collected cervical HPV tests, suggesting their potential utility for women who do not undergo regular cancer screening. However, the sensitivity was not high in spot urine. Therefore, further large-scale studies are needed to verify these findings and optimize testing methods to encourage broader participation in cancer screening programs.

5142 Pheochromocytoma In The ICU- Hiding In Plain Sight

Abstract Disclosure: N. Chandrashekar: None. B. Arafah: None. Introduction: Pheochromocytomas are catecholamine-secreting tumors that are rare but dangerous and occur in <0.2% of patients with hypertension. Case: A 28 year old female with a 10 year history of hypertension and invasive stage 2b cervical cancer s/p chemoradiation presented to the hospital with circulatory shock from Takutsubo cardiomyopathy requiring intubation, vasopressors, CVVH, and ECMO. The endocrinology service was consulted due to a highly vascular, 3.6 cm, ∼23 Hounsfield units right adrenal mass evidenced on CT abdomen done months prior to admission. There were elevations in plasma normetanephrine to 15 nmol/L (ref <0.90 nmol/L), plasma metanephrine to 1.5 nmol/L (ref <0.50 nmol/L), urinary metanephrine to 565 ug/24-hours (ref 36 - 209 ug/24-hr), and urinary normetanephrine to 2580 ug/24-hr (ref 95 - 449 ug/24-hr). With her acute illness and recent use of vasopressors and quetiapine, these labs could not be accurately interpreted, and outpatient follow up was recommended. She was discharged home on metoprolol and hydralazine for hypertension management by her primary team. She was re-admitted to the CICU 2 days later for hypertensive emergency with flash pulmonary edema. With further questioning, she endorsed longstanding hypertension with episodes of headaches, palpitations, and vomiting. Her cancer therapy related menopause caused frequent nighttime hot flashes while inpatient. These episodes precipitated witnessed symptoms of catecholamine release with severe hypertension and palpitations. It was noted during her hospitalization that her symptoms were controlled during the day with frequent escape during the night despite continuous alpha and subsequent beta blockade every 6 hrs. Estrogen therapy would have been beneficial, however given a recent DVT, this was avoided and instead megestrol acetate and venlafaxine were used. With these additions, her adrenergic spells completely resolved. She then underwent a right adrenalectomy and had no significant fluctuations in her BP intraoperatively with complete resolutions of symptoms postoperatively. The pathology revealed a right 2.7 cm pheochromocytoma with no local invasion or distant metastasis. Conclusion: This is a case of pheochromocytoma crisis with cardiogenic shock followed by subsequent hypertensive emergency in the setting of inappropriate beta-blocker use. Confounders like vasopressors (increases catecholamines), intrinsic stress of critical illness (increases catecholamines), and quetiapine use (can increase normetanephrine levels) make it difficult to analyze labs. In these cases, a thorough history and imaging are key to establishing a diagnosis and initiating life-saving treatment. Another unique feature of this case is the control of the patient’s triggering menopausal hot flashes with megace and venlafaxine to preempt adrenergic spells during her admission. Presentation: 6/2/2024

Status of uterine cervix cancer mortality and incidence disparities in Appalachian eastern Kentucky.

132 Background: Cervical cancer continues to affect the Appalachian population to a higher degree than the rest of the American population. Researchers believe the increased prevalence of cervical cancer in the Appalachian area is due to health disparities across the area. Methods: We queried the Kentucky Cancer Registries online public Cancer Incidence and Mortality Inquiry System to determine changes in age adjusted invasive cervical cancer incidence and mortality rates in Appalachian (AK) and Non-Appalachian Kentucky (NAK) counties over time. Incidence rate ratios were used to analyze the difference in cervical cancer incidence and mortality between Appalachian KY and non-Appalachian KY populations across several time periods. Results: In 1995-1999, there was a statistically significant difference in cervical cancer incidence between AK and NAK 14.8 vs. 12.7/100,000 people (p= 0.0035) and mortality 4.6 vs. 4.0/100,000 (p=0.0471). The cervical cancer incidence was 16.9% higher in AK versus NAK and mortality was 18.4% higher in AK versus NAK. In 2016-2020, there was a statistically significant difference in cervical cancer incidence between AK and NAK 12.1 vs. 8.9/100,000 people (p≤ 0.0001) and mortality between AK and NAK 3.6 vs. 2.3/100,000 people (p= 0.0001). The cervical cancer incidence was 36% higher in AK versus NAK and mortality was 55.7% higher in AK versus NAK. Conclusions: Disparities between in Appalachian Kentucky and Non-Appalachian Kentucky in cervical cancer incidence and mortality not only have persisted since the 1990’s, but they have widened proportionally over time as survival gains have lagged in Appalachia. The observed cervical cancer outcome disparities are likely contributed to by not only the lack of general health education in the region, but more importantly barriers to care access contributing to a lower use of Pap testing in the area. Higher rates of poverty, increased rates of smoking and HPV infection also likely play a role. Research has been conducted to observe identified opportunities for intervention and begin collaborative efforts in the region engineered towards a cervical cancer risk reduction program, but the need for improvement clearly remains. Cervical cancer mortality rates in Appalachian Kentucky vs. non-Appalachian Kentucky, 1995-2020. Appalachia Non-Appalachia Population at Risk Deaths Crude Rate/100,000 Age-Adjusted Rate 95% Confidence Interval Population at risk Deaths Crude Rate/100,000 Age-Adjusted Rate 95% Confidence Interval 1995-1999 2928468 145 5 4.6 [3.9-5.4] 7209127 301 4.2 4 [3.6-4.5] 2000-2004 2962204 102 3.4 3.2 [2.6-3.9] 7485965 214 2.9 2.7 [2.3-3.1] 2005-2009 2986284 117 3.9 3.5 [2.9-4.2] 7833348 225 2.9 2.6 [2.3-3.0] 2010-2015 3577269 141 3.9 3.4 [2.8-4.0] 9803897 277 2.8 2.5 [2.2-2.9] 2016-2020 2941022 121 4.1 3.6 [3.0-4.4] 8378683 221 2.6 2.3 [2.0-2.7]

S2840 Invasive Cervical Cancer as a Novelly Identified Cause of Colouterine Fistula

S2840 Invasive Cervical Cancer as a Novelly Identified Cause of Colouterine Fistula

Entangled Connections: HIV and HPV Interplay in Cervical Cancer-A Comprehensive Review.

Cervical cancer (CC) remains a prevalent malignancy and a significant global public health concern, primarily driven by persistent human papillomavirus (HPV) infections. The infectious nature of HPV underscores the preventability of CC through vaccination and screening programs. In addition to HPV, factors such as age, parity, smoking, hormonal contraceptives, and HIV co-infection elevate the risk of CC. HIV-associated immunodeficiency exacerbates susceptibility to infections and cancers, making CC a defining condition for acquired immune deficiency syndrome (AIDS) and one of the most commonly diagnosed cancers among women living with HIV (WLWH). These women face higher risks of HPV exposure due to sexual behavior and often encounter economic, social, and psychological barriers to screening. HIV and HPV co-infection can potentially accelerate CC carcinogenesis, with WLWH typically being diagnosed with CC earlier than their HIV-negative counterparts. Antiretroviral therapy (ART), which reduces AIDS-related mortality, also lowers the risk of invasive CC. The interaction between HIV and HPV is intricate and bidirectional. This summary reviews current evidence on HPV infection and CC in WLWH, highlighting the connections across pathogenesis, prevention, diagnosis, and treatment.

Cervical cancer microbiome analysis: comparing HPV 16 and 18 with other HPV types

Differences in the cervicovaginal microbiome may influence the persistence of HPV and therefore, the progression to cervical cancer. We aimed to analyze and compare the metatranscriptome of cervical cancers positive for HPV 16 and 18 with those positive for other HPV types to understand the microbiome’s influence on oncogenicity. RNA sequencing data from a total of 222 invasive cervical cancer cases (HPV16/18 positive (n=42) and HPV “Other types” (n=180)) were subjected to taxonomy classification (Kraken 2) including bacteria, virus and fungi to the level of species. With a median depth of 288,080.5 reads per sample, up to 107 species (38 bacterial, 16 viral and 53 fungal) were identified. Diversity analyses revealed no significant differences in viral or fungal species between HPV16/18 and other HPV types. Bacterial alpha diversity was significantly higher in the "Other HPV types" group for the Observed index (p=0.0074) (but not for Shannon). Cumulative species curves revealed greater species diversity in the “Other HPV types” group compared to “HPV16/18 but no significant differences in species abundance were found between HPV groups. The study did not detect strong significant microbiome differences between HPV 16/18 and other HPV types in cervical cancers. Further research is necessary to explore potential factors influencing the oncogenicity of different HPV types and their interaction with the cervical microbiome.

Relationship Between Serum Copper, Zinc Level and Tumour Aggressiveness in Invasive Cervical Cancer

<i>Background: </i>Cervical cancer, a leading cause of cancer-related morbidity and mortality, exhibits considerable variability in aggressiveness. The role of trace elements such as copper and zinc in influencing tumor behavior and progression has garnered attention. This study investigates the relationship between serum copper and zinc levels and tumor aggressiveness in invasive cervical cancer.<i> Methods:</i> A cross-sectional comparative study was conducted among 150 women with invasive cervical cancer attending the outpatient department and Colposcopy Clinic of the Department of Gynecological Oncology, BSMMU, Dhaka, from April 2022 to March 2023. Participants were divided into two groups based on tumor aggressiveness: Group 1 (less aggressive) and Group 2 (more aggressive), with 75 women in each group. Serum copper and zinc levels were measured and analyzed for differences between groups. <i>Result:</i> Serum copper levels were significantly higher in Group 2 (152.31 ± 41.81 µg/dL) compared to Group 1 (139.31 ± 25.52 µg/dL) with a p-value of 0.023. Conversely, serum zinc levels were significantly lower in Group 2 (55.24 ± 28.13 µg/dL) compared to Group 1 (66.29 ± 31.58 µg/dL) with a p-value of 0.025. The copper/zinc ratio was significantly higher in Group 2 (2.76 ± 1.20) compared to Group 1 (2.10 ± 1.00) with a p-value of <0.001. <i>Conclusion:</i> Elevated serum copper levels and copper/zinc ratio, along with decreased zinc levels, are associated with more aggressive cervical cancer. These findings suggest that trace element imbalances may serve as biomarkers for assessing tumor aggressiveness and could inform future therapeutic strategies.

Cervical Cancer Screening and Prevention Uptake in Females with Autism Spectrum Disorder.

This study reports on uptake rates of cervical cancer prevention and screening in a clinically-referred cohort of adolescent and adult females with autism spectrum disorder (ASD). Females with ASD (11-65years) were invited to participate in an online survey to report on uptake of the human papillomavirus (HPV) vaccination and cervical cancer screening. Participants also provided demographic and clinical information. Chi-square statistical analysis was utilized to examine the relationship between categorical variables and receipt of cervical cancer prevention and screening. Forty-one out of 73 (56%) of adolescent (11-17years) and 51/108 (47%) of adult (≥ 18years) females with ASD reported having received at least one dose of the HPV vaccine. Only 30/73 (41%) and 37/108 (34%) of adolescents and adults respectively, were fully vaccinated (≥ 2 doses). Language impairment was the only clinical factor found to be associated with non-receipt of the HPV vaccine. Thirty-one out of 82 (38%) adult females (≥ 21years) with ASD had received at least one pap smear. Language impairment, intellectual disability, non-independent living, and lower level of education were all associated with not receiving a pap smear. Females with ASD are vulnerable to invasive cervical cancer disease due to low uptake rates of the HPV vaccine and routine pap smear screening.

Somatic mutations in 3929 HPV positive cervical cells associated with infection outcome and HPV type

Invasive cervical cancers (ICC), caused by HPV infections, have a heterogeneous molecular landscape. We investigate the detection, timing, and HPV type specificity of somatic mutations in 3929 HPV-positive exfoliated cervical cell samples from individuals undergoing cervical screening in the U.S. using deep targeted sequencing in ICC cases, precancers, and HPV-positive controls. We discover a subset of hotspot mutations rare in controls (2.6%) but significantly more prevalent in precancers, particularly glandular precancer lesions (10.2%), and cancers (25.7%), supporting their involvement in ICC carcinogenesis. Hotspot mutations differ by HPV type, and HPV18/45-positive ICC are more likely to have multiple hotspot mutations compared to HPV16-positive ICC. The proportion of cells containing hotspot mutations is higher (i.e., higher variant allele fraction) in ICC and mutations are detectable up to 6 years prior to cancer diagnosis. Our findings demonstrate the feasibility of using exfoliated cervical cells for detection of somatic mutations as potential diagnostic biomarkers.

Ranking the attribution of high-risk genotypes among women with cervical precancers and cancers: a cross-sectional study in Ningbo, China

BackgroundThe region-specific importance of carcinogenic HPV genotypes is required for optimizing HPV-based screening and promoting appropriate multivalent HPV prophylactic vaccines. This information is lacking for Ningbo, one of the first cities of China’s Healthy City Innovation Pilot Program for Cervical Cancer Elimination. Here, we investigated high-risk HPV (HR-HPV) genotype-specific distribution and attribution to biopsy-confirmed cervical intraepithelial neoplasia grade 2 or worse (CIN2+) before mass vaccination in Ningbo, China.MethodsA total of 1393 eligible CIN2+ archived blocks (including 161 CIN2, 1107 CIN3, and 125 invasive cervical cancers [ICC]) were collected from 2017 to 2020 in Ningbo. HR-HPV DNA was genotyped using the SPF10-DEIA-LiPA25 version 1 detection system and the SureX HPV 25X Genotyping Kit. Genotype-specific attribution to CIN2+ was estimated using a fractional contribution approach.ResultsRanking by the attributable proportions, HPV16 remained the most important genotype in both cervical precancers and cancers, accounting for 36.8% of CIN2, 53.2% of CIN3, and 73.3% of ICC cases. Among cervical precancers, HPV52 (17.3% in CIN2, 12.7% in CIN3) and HPV58 (13.9%, 14.9%) ranked second and third, while HPV33 (8.3%, 7.9%) and HPV31 (6.5%, 4.1%) ranked fourth and fifth, respectively. However, among ICCs, HPV18 (5.7%) accounted for the second highest proportion, followed by HPV33 (5.4%), HPV58 (4.0%), and HPV45 (3.2%). HPV18/45 together accounted for 46.8% of adenocarcinomas, which was slightly lower than that of HPV16 (47.7%). The remaining HR-HPV genotypes (HPV35/39/51/56/59/66/68) combined accounted for only 6.7% of CIN2, 2.9% of CIN3, and 4.2% of ICC.ConclusionsWith Ningbo’s strong medical resources, it will be important to continue HPV16/18 control efforts, and could broaden to HPV31/33/45/52/58 for maximum health benefits. However, different strategies should be proposed for other HR-HPV genotypes based on their lower carcinogenic risks.

Unexpectedly Good Results from Advanced Invasive Cervical Cancer: Palliative Surgery

Presentation with a highly infiltrated malignant lesion often leads to unfavorable outcomes. This woman exhibited an advanced form of cervical cancer that had spread to the surrounding tissue, which might involve the urinary bladder. Due to the Sudan War in 2023, there was a lack of oncological therapy. In response, we implemented palliative surgery, which yielded positive results.

Head-to-head comparison of two human papillomavirus vaccines for efficacy against cervical intraepithelial neoplasia grade 3 and adenocarcinoma in situ-population-based follow-up of two cluster-randomized trials.

We report head-to-head comparison of the bivalent and quadrivalent HPV vaccine efficacies against immediate precursors of cervical cancer from 15 years' country-wide cancer registry follow-up of phase III trial cohorts and an age-aligned cohort of unvaccinated women. These individually and/or clusterrandomized cohorts of HPV6/11/16/18- and HPV16/18-vaccinated and unvaccinated women were enrolled, respectively, in 2002, 2004, and 2003/2005. The trial cohorts comprised initially 16- to 17-year-old HPV6/11/16/18-vaccinated FUTURE II (NCT00092534) participants (866) and HPV16/18-vaccinated PATRICIA (NCT00122681) and 012 trial (NCT00169494) participants (2,465), and 16,526 initially 16- to 19-year-old unvaccinated controls. After active 4-year clinical follow-up, passive, country-wide Finnish Cancer Registry (FCR) follow-up for cervical intraepithelial neoplasia grade 3 (CIN3) and adenocarcinoma in situ (AIS) was based on consented use of unique personal identifiers and started 6 months after the end of the FUTURE II and PATRICIA trials in 2007 and 2009, and ended at the end of 2019. The follow-up with altogether 229,020 follow-up years was age-aligned to ensure that similarly aged cohorts were passively followed up for 15 years post=vaccination for the intention-to-treat analyses of vaccine efficacy. Overall, we identified 5 and 16 CIN3 (no AIS) cases in the HPV6/11/16/18 and HPV16/18 cohorts, respectively, during the FCR-based follow-up. In the unvaccinated cohort, we identified 281 CIN3 cases, 20 AIS cases, and 13 cases with invasive cervical cancer. Vaccine efficacies against CIN3+ were 68.4% and 64.5% for the quadrivalent and the bivalent vaccines, respectively, with overlapping confidence intervals. Long-term follow-up of randomized, initially adolescent HPV-vaccinated and unvaccinated cohorts shows, in this head-to-head setting, that the bivalent and quadrivalent HPV vaccines are equally effective against immediate precursors of cervical cancer.

Human Papillomavirus Genotypes Distribution in High-Grade Cervical Lesions and Invasive Cervical Carcinoma in Women Living in Mauritania: Implications for Cervical Cancer Prevention and HPV Prophylactic Vaccination.

Cervical cancer related to high-risk human papillomavirus (HR-HPV) is the second female cancer in Mauritania (Northwest Sahelian Africa). We assessed the distribution of HPV genotypes in Mauritanian women with high-grade cervical intraepithelial neoplasia (CIN2/3) or invasive cervical cancer (ICC). A prospective study was conducted in the Centre Hospitalier National, Nouakchott, Mauritania, to collect cervical biopsies among women suspected of CIN2/3 or cancer. HPV DNA detection and genotyping were carried out from formalin-fixed, paraffin-embedded biopsies using multiplex PCR (Human Papillomavirus Genotyping Real-Time PCR Kit, Bioperfectus Technologies Co., Taizhou, China). Fifty biopsies were included from women (mean age: 56.7 years) suffering from CIN2/3 (28.0%) and ICC (72.0%) which corresponded to 32 (64.0%) squamous cell carcinomas (SCC) and 4 (8.0%) adenocarcinomas (ADC). HPV DNA detection was successful in 47 (94.0%) samples. The most prevalent HR-HPV genotypes were HPV-45 (40.4%), HPV-16 (38.3%), HPV-39 and HPV-52 (23.4%), HPV-33 (17.0%), HPV-18 (14.9%), HPV-35 (4.2%), and HPV-56 (2.1%). The majority (93.6%) of HPV-positive biopsies contained at least one HPV type covered by the 9-valent Gardasil-9® vaccine, and 40.9% were infected by multiple vaccine HPV genotypes. To eradicate cervical cancer in Mauritania, prophylactic HPV vaccination must be combined with primary molecular screening of cervical HR-HPV infection.

Cervical precancer and invasive cancer among women living with HIV in Latin America: A systematic review and meta-analysis.

Data on the occurrence of cervical precancer and cancer among women living with HIV (WLHIV) in Latin American countries (LAC) are scarce and highly heterogeneous. We conducted a systematic review summarizing data about the incidence/prevalence of invasive cervical cancer (CC) and high-grade precancerous lesions among WLHIV in LAC. Literature in PubMed and LILACS was searched. The primary outcome was invasive cancer incidence, and prevalence of high-grade lesions as key indicators for the WHO CC elimination strategy. Individual reports on invasive cancer incidence and prevalence of precancerous lesions were obtained, and a random effects meta-analysis was conducted for the latter. In total, 34,343 WLHIV from four studies reporting CC incidence in seven LAC were included, and 6079 WLHIV from 17 studies reporting prevalence of precancerous lesions in three LAC were included. CC incidence ranged between 136.0 and 398.4 per 100,000 WLHIV (with or without antiretroviral therapy). The weighted prevalence of high-grade lesions was 4.1% (95%CI: 3.8%-6.0%) with a double peak at ages 20-24 and 35-39 years. Differences in prevalence of high-grade lesions were also observed by screening approach: co-testing (11.9%), colposcopy (6.0%), cytology (4.2%), and HPV tests (3.2%). The high incidence of invasive cancer and prevalence of high-grade lesions underline challenges to reach the WHO's elimination goal of CC incidence below four per 100,000 among WLHIV. Moreover, the high prevalence of high-grade lesions at younger ages than in the general population is a call to accelerate the implementation of the new WHO screening recommendations in WLHIV.

Changes in the molecular nodes of the Notch and NRF2 pathways in cervical cancer tissues from the precursor stages to invasive carcinoma.

Cancer is a multifactorial disease characterized by the loss of control in the expression of genes known as cancer driver genes. Cancer driver genes trigger uncontrolled cell replication, which leads to the development of malignant tumors. A cluster of signal transduction pathways that contain cancer driver genes involved in cellular processes, such as cell proliferation, differentiation, apoptosis and dysregulated organ growth, are associated with cancer initiation and progression. In the present study, three signal transduction pathways involved in cervical cancer (CC) development were analyzed: The Hippo pathway (FAT atypical cadherin, yes-associated protein 1, SMAD4 and TEA domain family member 2), the Notch pathway [cellular-MYC, cAMP response element-binding binding protein (CREBBP), E1A-associated cellular p300 transcriptional co-activator protein and F-Box and WD repeat domain containing 7] and the nuclear factor erythroid 2-related factor 2 (NRF2) pathway [NRF2, kelch-like ECH-associated protein 1 (KEAP1), AKT and PIK3-catalytic subunit α]. Tumor samples from patients diagnosed with various stages of CC, including cervical intraepithelial neoplasia (CIN) 1, CIN 2, CIN 3, in situ CC and invasive CC, were analyzed. The mRNA expression levels were analyzed using reverse transcription-quantitative PCR assays, whereas protein expression levels were assessed through immunohistochemical tissue microarrays. High mRNA expression levels of c-MYC and AKT and low expression levels of NRF2 and KEAP1 were associated with a decreased survival time of patients with CC. Additionally, increased expression levels of c-MYC were detected in the invasive CC stage. At the protein level, increased NRF2 expression levels were observed in all five stages of CC samples compared with those in the cancer-free control samples. AKT1 was found to be dysregulated in the CIN 1 and CIN 2 stages, PI3K in the in situ and invasive stages, and CREBBP in the CIN 3 and in situ stages. In summary, the present study demonstrated significant changes in proteins of the Notch and NRF2 pathways in CC. NRF2 was overexpressed in all cervical cancer stages (cervical intraepithelial neoplasia, in situ CC and invasive CC). The present study makes an important contribution to the possible biomarker proteins to be analyzed for the presence of premalignant and malignant lesions in the cervix.

Prevalence and genotype distribution of potential high-risk and high-risk human papillomavirus among women attending selected reproductive health clinics in lake victoria basin-kenya: a cross-sectional study

BackgroundPersistent human papillomavirus (HPV) infection is considered the primary etiological factor for invasive cervical cancer. Understanding the epidemiology of circulating potential high-risk (HR) and HR HPV strains is essential in updating epidemiological knowledge and recommendations on genotype-specific vaccination development. This study determined the prevalence and factors associated with Potential HR/HR HPV among women attending selected reproductive health clinics in Lake Victoria Basin.MethodsA cross-sectional facility-based survey made up of 434 women aged 16–68 years was carried out in two selected facilities. Structured questionnaires were administered to collect participant clinical and social characteristics. Cervical specimens were collected and HPV genotyping was carried out using RIATOL HPV genotyping qPCR assay. Descriptive statistics followed by logistic binary regression was done using R version 4.3.2.ResultsThe overall prevalence of potential HR/HR HPV among women attending the selected reproductive health clinics was reported at 36.5% (158/434). Specifically, in the rural setting, Gobei Health Center, the prevalence was 41.4% (41/99) while in the urban setting-JOOTRH, it was 34.6% (117/335). The most prevalent potential HR/HR HPV are 52, 67, 16, 31, 39, 45, and 31 among women. Age was the main factor associated with HPV infection with women between the age of 30–39 having the highest risk (AOR = 0.3, CI:0.2–0.7, p < 0.001).ConclusionIn both rural and urban regions, potential HR/HR HPV infection among women attending reproductive health clinics at the selected facilities remains common. The study identifies the need for effective implementation and clinical follow-up process of cervical cancer control program in the LVB.

Identification of HPV16 Lineages in South African and Mozambican Women with Normal and Abnormal Cervical Cytology.

Human papillomavirus 16 (HPV16) is an oncogenic virus responsible for the majority of invasive cervical cancer cases worldwide. Due to genetic modifications, some variants are more oncogenic than others. We analysed the HPV16 phylogeny in HPV16-positive cervical Desoxyribonucleic Acid (DNA) samples collected from South African and Mozambican women to detect the circulating lineages. Polymerase chain reaction (PCR) amplification of the long control region (LCR) and 300 nucleotides of the E6 region was performed using HPV16-specific primers on HPV16-positive cervical samples collected in women from South Africa and Mozambique. HPV16 sequences were obtained through Next Generation Sequencing (NGS) methods. Geneious prime and MEGA 11 software were used to align the sequences to 16 HPV16 reference sequences, gathering the A, B, C, and D lineages and generating the phylogenetic tree. Single nucleotide polymorphisms (SNPs) in the LCR and E6 regions were analysed and the phylogenetic tree was generated using Geneious Prime software. Fifty-eight sequences were analysed. Of these sequences, 79% (46/58) were from women who had abnormal cervical cytology. Fifteen SNPs in the LCR and eight in the E6 region were found to be the most common in all sequences. The phylogenetic analysis determined that 45% of the isolates belonged to the A1 sublineage (European variant), 34% belonged to the C1 sublineage (African 1 variant), 16% belonged to the B1 and B2 sublineage (African 2 variant), two isolates belonged to the D1-3 sublineages (Asian-American variant), and one to the North American variant. The African and European HPV16 variants were the most common circulating lineages in South African and Mozambican women. A high-grade squamous intraepithelial lesion (HSIL) was the most common cervical abnormality observed and linked to European and African lineages. These findings may contribute to understanding molecular HPV16 epidemiology in South Africa and Mozambique.