Natural History Of Cervical Cancer Research Articles

The level of expression of HPV16 early transcripts is not associated with the natural history of cervical lesions.

The natural history of cervical cancer is closely linked to that of high-risk human papillomaviruses (HPV) infection. It is recognized that upon HPV DNA integration, partial or complete loss of the E2 open reading frame precludes expression of the corresponding protein, resulting in upregulation of the E6 and E7 viral oncoproteins. To better characterize HPV16 infection at the cervical level, viral load, viral DNA integration, and viral early transcript expression (E2, E5, and E6) were analyzed in a series of 158 cervical specimens representative of the full spectrum of cervical disease. Overall, the frequency of early transcript detection varied from 45% to 90% and tended to increase with lesion severity. In addition, the levels of E2, E5, and E6 transcript expression were slightly higher in high-grade lesions than in cervical specimens without abnormalities. Notably, early transcript expression was clearly associated with viral load, and no inverse correlation was found between the expression of E2 and E6 transcripts. No clear association was found between early transcript expression and HPV16 DNA integration, with the exception that samples with a fully integrated HPV16 genome did not harbor E2 or E5 transcripts. In conclusion, early HPV16 transcript expression appears to be associated with viral load rather than lesion grade. From a practical point of view, quantification of HPV16 early transcripts is difficult to translate into a relevant biomarker for cervical cancer screening.

Economic Evaluation of Cervical Cancer Screening by HPV DNA, VIA, and Pap smear Methods in Indonesia.

Cervical cancer occurs 80% in developing country including Indonesia and take place in the first rank of incidence rate and third rank in mortality rate in Asian Pacific. Natural history of cervical cancer gives a potential to get accurate screening method. Cervical cancer screening m in Indonesia use VIA and Pap smear method for women in age range 30 to 50 years old. Recently, HPV DNA test has been recommended in international and national policy as primary screening method for cervical cancer. This research aims to asses cost-effectiveness and economic implications of specific cervical cancer screening modalities. Cost-effectiveness analysis was conducted from societal perspective. Cost data was collected from four hospitals in Indonesia. Direct medical costs were derived from discussions with an expert panel and hospital billing data, aligning with current practice guidelines. Direct and indirect non-medical costs were estimated from patient interviews. Effectiveness data for the screening methods were extracted from a systematic review of existing literature. Markov model design was used for cost-effectiveness analysis. Budget impact analysis used healthcare perspective method from its billing for cervical cancer patients. Cervical cancer screening costs are calculated using direct medical, non-medical, and indirect expenses. Regarding to cost-effective analysis by incremental cost-effective ratio (ICER), pap smear for every 3 and 5 years is more cost-effective than VIA. HPV DNA also has the potential to be cost-effective. The budget impact analysis investigates scenarios, with a focus on negotiation-based cost reductions for HPV DNA testing. Controlling HPV DNA tariffs at USD 8.76 proves cost-effective. In conclusion, pap smear is the most cost-effective modality, while HPV DNA has the potential to be cost-effective by reducing the unit cost. Despite favorable outcomes, challenges in implementation suggest a phased approach for resource equalization before full deployment.

A health decision analytical model to evaluate the cost-effectiveness of female genital schistosomiasis screening strategies: The female genital schistosomiasis SCREEN framework.

Female genital schistosomiasis is a chronic gynaecological disease caused by the waterborne parasite Schistosoma (S.) haematobium. It affects an estimated 30-56 million girls and women globally, mostly in sub-Saharan Africa where it is endemic, and negatively impacts their sexual and reproductive life. Recent studies found evidence of an association between female genital schistosomiasis and increased prevalence of HIV and cervical precancer lesions. Despite the large population at risk, the burden and impact of female genital schistosomiasis are scarcely documented, resulting in neglect and insufficient resource allocation. There is currently no standardised method for individual or population-based female genital schistosomiasis screening and diagnosis which hinders accurate assessment of disease burden in endemic countries. To optimise financial allocations for female genital schistosomiasis screening, it is necessary to explore the cost-effectiveness of different strategies by combining cost and impact estimates. Yet, no economic evaluation has explored the value for money of alternative screening methods. This paper describes a novel application of health decision analytical modelling to evaluate the cost-effectiveness of different female genital schistosomiasis screening strategies across endemic settings. The model combines a decision tree for female genital schistosomiasis screening strategies, and a Markov model for the natural history of cervical cancer to estimate the cost per disability-adjusted life-years averted for different screening strategies, stratified by HIV status. It is a starting point for discussion and for supporting priority setting in a data-sparse environment.

Strategies to accelerate the elimination of cervical cancer in British Columbia, Canada: a modelling study.

To eliminate cervical cancer in Canada by 2040, defined as an annual age-standardized incidence rate (ASIR) lower than 4.0 per 100 000 women, the Canadian Partnership Against Cancer (CPAC) identified 3 priorities for action: increasing human papillomavirus (HPV) vaccine coverage, implementing HPV-based screening and increasing screening participation, and improving follow-up after abnormal screen results. Our objective was to explore the impact of these priorities on the projected time to elimination of cervical cancer in British Columbia. We used OncoSim-Cervical, a microsimulation model led and supported by CPAC and developed by Statistics Canada that simulates HPV transmission and the natural history of cervical cancer for the Canadian population. We updated model parameters to reflect BC's historical participation rates and program design. We simulated the transition to HPV-based screening and developed scenarios to explore the additional impact of achieving 90% vaccination coverage, 95% screening recruitment, 90% ontime screening, and 95% follow-up compliance. We projected cervical cancer incidence, ASIR, and year of elimination for the population of BC for 2023-2050. HPV-based screening at current vaccination, participation, and follow-up rates can eliminate cervical cancer by 2034. Increasing on-time screening and follow-up compliance could achieve this target by 2031. Increasing vaccination coverage has a small impact over this time horizon. With the implementation of HPV-based screening, cervical cancer can be eliminated in BC before 2040. Efforts to increase screening participation and follow-up through this transition could potentially accelerate this timeline, but the transition from cytology- to HPV-based screening is fundamental to achieving this goal.

Cost-effectiveness of single-visit cervical cancer screening in KwaZulu-Natal, South Africa: a model-based analysis accounting for the HIV epidemic.

Women living with human immunodeficiency virus (WLHIV) face elevated risks of human papillomavirus (HPV) acquisition and cervical cancer (CC). Coverage of CC screening and treatment remains low in low-and-middle-income settings, reflecting resource challenges and loss to follow-up with current strategies. We estimated the health and economic impact of alternative scalable CC screening strategies in KwaZulu-Natal, South Africa, a region with high burden of CC and HIV. We parameterized a dynamic compartmental model of HPV and HIV transmission and CC natural history to KwaZulu-Natal. Over 100 years, we simulated the status quo of a multi-visit screening and treatment strategy with cytology and colposcopy triage (South African standard of care) and six single-visit comparator scenarios with varying: 1) screening strategy (HPV DNA testing alone, with genotyping, or with automated visual evaluation triage, a new high-performance technology), 2) screening frequency (once-per-lifetime for all women, or repeated every 5 years for WLHIV and twice for women without HIV), and 3) loss to follow-up for treatment. Using the Ministry of Health perspective, we estimated costs associated with HPV vaccination, screening, and pre-cancer, CC, and HIV treatment. We quantified CC cases, deaths, and disability-adjusted life-years (DALYs) averted for each scenario. We discounted costs (2022 US dollars) and outcomes at 3% annually and calculated incremental cost-effectiveness ratios (ICERs). We projected 69,294 new CC cases and 43,950 CC-related deaths in the status quo scenario. HPV DNA testing achieved the greatest improvement in health outcomes, averting 9.4% of cases and 9.0% of deaths with one-time screening and 37.1% and 35.1%, respectively, with repeat screening. Compared to the cost of the status quo ($12.79 billion), repeat screening using HPV DNA genotyping had the greatest increase in costs. Repeat screening with HPV DNA testing was the most effective strategy below the willingness to pay threshold (ICER: $3,194/DALY averted). One-time screening with HPV DNA testing was also an efficient strategy (ICER: $1,398/DALY averted). Repeat single-visit screening with HPV DNA testing was the optimal strategy simulated. Single-visit strategies with increased frequency for WLHIV may be cost-effective in KwaZulu-Natal and similar settings with high HIV and HPV prevalence.

Microbiome markers in HPV-positive and HPV-negative women of reproductive age with ASCUS and SIL determined by V4 region of 16S rRNA gene sequencing.

Human papilloma virus (HPV) is the most common sexually transmitted infection worldwide. Cervicovaginal microbiota plays an important role in HPV infection and is associated with the development of squamous intraepithelial lesions (SIL). The natural history of cervical cancer involves reversible changes in the cervical tissue from a normal state, in which no neoplastic changes are detected in the squamous epithelium, to varying states of cellular abnormalities that ultimately lead to cervical cancer. Low-grade SIL (LSIL), like another cytological category - atypical squamous cells of undetermined significance (ASCUS), may progress to high-grade SIL (HSIL) and invasive cervical cancer or may regress to a normal state. In this work, we studied cervical canal microbiome in 165 HPV-positive and HPV-negative women of a reproductive age with ASCUS [HPV(+) n = 29; HPV(-) n = 11], LSIL [HPV(+) n = 32; HPV(-) n = 25], HSIL [HPV(+) n = 46], and the control group with negative for intraepithelial lesion malignancy (NILM) [HPV(-) n = 22]. HPV16 is the most prevalent HPV type. We have not found any differences between diversity in studied groups, but several genus [like Prevotella (p-value = 0.026), Gardnerella (p-value = 0.003), Fannyhessea (p-value = 0.024)] more often occurred in HSIL group compared by NILM or LSIL regardless of HPV. We have found statistically significant difference in occurrence or proportion of bacterial genus in studied groups. We also identified that increasing of the ratio of Lactobacillus iners or age of patient lead to higher chance to HSIL, while increasing of the ratio of Lactobacillus crispatus lead to higher chance to LSIL. Patients with a moderate dysbiosis equally often had either of three types of vaginal microbial communities (CST, Community State Type) with the prevalence of Lactobacillus crispatus (CST I), Lactobacillus gasseri (CST II), and Lactobacillus iners (CST III); whereas severe dysbiosis is linked with CST IV involving the microorganisms genera associated with bacterial vaginosis and aerobic vaginitis: Gardnerella, Fannyhessea, Dialister, Sneathia, Anaerococcus, Megasphaera, Prevotella, Finegoldia, Peptoniphilus, Porphyromonas, Parvimonas, and Streptococcus.

Prevalence of Precancerous Cervical Lesions among Nonvaccinated Kazakhstani Women: The National Tertiary Care Hospital Screening Data (2018).

At the present time, cervical cancer remains the fourth most prevalent cancer among women worldwide. Most cervical cancer cases are attributed to high-risk human papillomavirus (HPV) infection. Because the natural history of cervical cancer takes decades, the disease could be prevented if premalignant conditions are identified and appropriately managed. The aim of this study is to identify the prevalence of precancerous lesions among non-vaccinated women attending the national tertiary care hospital in Kazakhstan. This was a retrospective study of the cervical cancer screening database (2018) from the national tertiary care hospital in Kazakhstan. Records of 6682 patients, who had cervical cytology tests by Papanicolaou (Pap test), were analyzed. Out of the revised cases, 249 patients had abnormal cervical cytology reports. The Pap test was performed using liquid-based cytology (LBC). The data were analyzed using the statistical software STATA 16. A p-value of less than 0.05 was considered statistically significant. In this retrospective analysis of 6682 patients' records, we found 3.73% (249 patients) out of all Pap tests performed in 2018 were abnormal. The prevalence of high-grade squamous intraepithelial lesion (HSIL) was high at 19.28%, and the proportion of atypical squamous cells of undetermined significance (ASCUS) and atypical squamous cells (ASCs-H) was 18.47%, while low-grade squamous intraepithelial lesion (LSIL) were identified in 62.25% of the cases. Almost 25% of the women included in the study had concurrent lower and upper genital tract infections. Although the overall rate of abnormal Pap test results was not high, the study shows the elevated prevalence of HSIL. It calls the attention of local policymakers and gynecology specialists and requires immediate actions to improve the prophylactic measures to decrease morbidity and mortality from cervical cancer in Kazakhstan.

Evaluation of the Cytonucleomorphometric Parameters for Cases Diagnosed as Squamous Cell Abnormality on Conventional Cervico-Vaginal Pap Smears.

The natural history of cervical cancer is unique that it is preceded by a precancerous condition for a long time. Morphometry as a tool can be used in early and accurate diagnosis of these precancerous and cancerous lesions. The present study aims at assessing the utility of cellular and nuclear morphometry in differentiating squamous cell abnormality from benign conditions and also differentiating the categories of squamous cell abnormalities. Forty-eight diagnosed cases of squamous epithelial cell abnormality, that is, 10 cases each of atypical squamous cell of undetermined significance (ASC-US), low-grade squamous intraepithelial lesion (LSIL), high-grade SIL (HSIL), and squamous cell carcinoma (SCC) and eight cases of ASC-H (ASC cannot exclude HSIL), were made the sample population and compared with a control population of 10 cases of negative for intraepithelial lesion or malignancy (NILM). Parameters like nuclear area (NA), nuclear perimeter (NP), nuclear diameter (ND), nuclear compactness (NC), cellular area (CA), cellular diameter (CD), cellular perimeter (CP), and nucleocytoplasmic (N/C) ratio were used. There was a significant difference in the six groups of squamous cell abnormality based on NA, NP, ND, CA, CP, and CD (P < 0.05) using one-way analysis of variance. Nuclear morphometry parameters like NA, NP, and ND were found to be the maximum for HSIL, followed by LSIL, ASC-H, ASC-US, SCC, and NILM groups in decreasing order. The mean CA, CP, and CD were found to be the maximum for NILM, followed by LSIL, ASC-US, HSIL, ASC-H, and SCC in decreasing order. On post hoc analysis, the lesions can be divided into three groups: NILM/normal; ASC-US and LSIL; and ASC-H, HSIL, and SCC, based on N/C ratio. In cervical lesions, holistic parameter of cytonucleomorphometry should be taken rather than taking nuclear morphometry only. N/C ratio is a highly statistically significant parameter that can differentiate between low-grade lesions and high-grade lesions.

The Clinical and Economic Impact of a Nonavalent Versus Bivalent Human Papillomavirus National Vaccination Program in Taiwan

This study aimed to estimate the epidemiologic and economic impact of a nonavalent human papillomavirus (HPV) vaccination program for 13- to 14-year-old females compared with that of the bivalent vaccine in Taiwan. A previously developed dynamic transmission model for the nonavalent HPV vaccine was adapted to the Taiwan setting. The natural history of cervical cancer and genital warts was simulated by the HPV model assuming an 80% vaccination coverage rate in girls aged 13 to 14 years of age with a 2-dose schedule for the nonavalent and bivalent HPV vaccines. A lifetime duration of vaccine protection was assumed for the HPV vaccine types. The model estimated that the nonavalent HPV vaccine would prevent an additional 15 951 cervical cancer cases, 6600 cervical cancer-related deaths, 176 702 grade 2 or grade 3 cervical intraepithelial neoplasia cases, 103 959 grade 1 cervical intraepithelial neoplasia cases, and 1 115 317 genital warts cases compared with the bivalent HPV vaccine. The nonavalent HPV vaccination program was projected to cost an additional New Taiwan dollars (NTD) 675.21 per person and to produce an additional 0.00271 quality-adjusted life-year per person over 100 years compared with the bivalent HPV vaccine. Thus, the incremental cost-effectiveness ratio of the nonavalent HPV vaccine versus the bivalent HPV vaccine was NTD 249 462/quality-adjusted life-year. A nonavalent HPV vaccination program for 13- to 14-year-old girls would have additional public health and economic impacts and would be highly cost-effective compared with the bivalent HPV vaccine, relative to per capita gross domestic product, which is estimated at NTD 746 526 for Taiwan.

Cost-effectiveness analysis of the 2019 American Society for Colposcopy and Cervical Pathology Risk-Based Management Consensus Guidelines for the management of abnormal cervical cancer screening tests and cancer precursors

The guidelines for managing abnormal cervical cancer screening tests changed from a results-based approach in 2012 to a risk-based approach in 2019. We estimated the cost-effectiveness of the 2019 management guidelines and the changes in resource utilization moving from 2012 to 2019 guidelines. We utilized a previously published model of cervical cancer natural history and screening to estimate and compare the lifetime costs and the number of screens, colposcopies, precancer treatments, cancer cases, and cancer deaths associated with the 2012 vs 2019 management guidelines. We assessed these guidelines under the scenarios of observed screening practice and perfect screening adherence to 3-year cytology starting at age 21, with a switch to either 3-year or 5-year cytology plus human papillomavirus cotesting at age 30. In addition, we estimated the lifetime costs and life years to determine the cost-effectiveness of shifting to the 2019 management guidelines. Under the assumptions of both observed screening practice and perfect screening adherence with a strategy of 3-year cytology at ages 21 to 29 and switching to 3-year cotesting at age 30, the management of the screening tests according to the 2019 guidelines was less costly and more effective than the 2012 guidelines. For 3-year cytology screening at ages 21 to 29 and switching to 5-year cotesting at age 30, the 2019 guidelines were more cost-effective at a willingness-to-pay threshold of $100,000 per life year gained. Across all scenarios, the 2019 management guidelines were associated with fewer colposcopies and cancer deaths. Our model-based analysis suggests that the 2019 guidelines are more effective overall and also more cost-effective than the 2012 guidelines, supporting the principle of "equal management of equal risks."

Meta-analysis of annual probability of outcome for different cervical disease states

Objective: To explore the annual probabilities of outcomes for different cervical disease states. Methods: Cohort studies related to the natural history of cervical cancer were retrieved from PubMed, Embase and China Biomedical Literature Database, and the retrieval time was from the establishment of the database to May 2020. Newcastle-Ottawa scale was used to evaluate the quality of the included literatures. The annual outcome probabilities of different cervical disease states in high-risk human papillomavirus (hrHPV) positive, negative and cervical intraepithelial neoplasia grade 1 (CIN1) population were calculated (95%CI). Random-effects model was used for meta-analysis. Egger's test was used to evaluate publication bias; sensitivity analysis was used to evaluate the robustness of the combined parameters. Meta-regression was used to explore factors associated with the heterogeneity of annual outcome probability. Results: A total of 37 studies were included, including 12, 20 and 15 studies involving hrHPV negative, hrHPV positive and CIN1 population, respectively, with a Newcastle -Ottawa scale (NOS) score of 7.05±1.20. The annual probability (95%CI) of progression to CIN1, CIN2 and CIN3+ in hrHPV-positive population were 0.022 2 (0.014 3, 0.031 0), 0.017 0 (0.012 0, 0.022 0) and 0.016 2 (0.012 6, 0.019 8), respectively. The annual probability (95%CI) of progression to CIN1, CIN2 and CIN3+ in hrHPV-negative population was 0.002 7 (0.000 9, 0.004 6), 0.000 7 (0.000 3, 0.001 1) and 0.000 6 (0.000 3, 0.000 9), respectively. The annual probability (95%CI) of reversal to normal, maintenance of CIN1 status and progression to cervical intraepithelial neoplasia grade 2 or above (CIN2+) in CIN1 population were 0.578 1 (0.369 9, 0.786 3), 0.400 1 (0.167 4, 0.632 9), 0.056 9 (0.034 9, 0.078 9), respectively. Egger's test showed that there was publication bias in the annual outcome probability of hrHPV positive progression to CIN2 and CIN3+ and hrHPV negative progression to CIN2 and CIN1 progression to CIN2+, with t values of 5.50, 2.36, 2.80 and 4.12, respectively (all P values<0.05). Sensitivity analysis showed that when excluding any of the studies, the range of annual probability of progression to CIN1, CIN2 and CIN3+ were 0.016 6-0.024 7, 0.014 9-0.018 9 and 0.013 6-0.017 7 among hrHPV-positive population; 0.002 4-0.003 5, 0.000 6-0.000 9 and 0.000 5-0.000 7 among hrHPV-negative population and the range of annual probability of CIN1 reversal to normal, maintenance as CIN1 and progression to CIN2+ were 0.531 8-0.631 2, 0.321 9-0.443 3, and 0.052 0-0.061 0, respectively. Meta-regression analysis showed that region, population origin, population cytological diagnosis, follow-up time, and NOS score were not associated with the heterogeneity of annual outcome probability (all P values>0.05). Conclusion: The annual outcome probability of different cervical disease states in hrHPV positive population is high, and the CIN1 population only needs close follow-up.

Impact of disruptions and recovery for established cervical screening programs across a range of high-income country program designs, using COVID-19 as an example: A modelled analysis

COVID-19 has disrupted cervical screening in several countries, due to a range of policy-, health-service and participant-related factors. Using three well-established models of cervical cancer natural history adapted to simulate screening across four countries, we compared the impact of a range of standardised screening disruption scenarios in four countries that vary in their cervical cancer prevention programs. All scenarios assumed a 6- or 12-month disruption followed by a rapid catch-up of missed screens. Cervical screening disruptions could increase cervical cancer cases by up to 5–6%. In all settings, more than 60% of the excess cancer burden due to disruptions are likely to have occurred in women aged less than 50 years in 2020, including settings where women in their 30s have previously been offered HPV vaccination. Approximately 15–30% of cancers predicted to result from disruptions could be prevented by maintaining colposcopy and precancer treatment services during any disruption period. Disruptions to primary screening had greater adverse effects in situations where women due to attend for screening in 2020 had cytology (vs. HPV) as their previous primary test. Rapid catch-up would dramatically increase demand for HPV tests in 2021, which it may not be feasible to meet because of competing demands on the testing machines and reagents due to COVID tests. These findings can inform future prioritisation strategies for catch-up that balance potential constraints on resourcing with clinical need.

Low RECK Expression Is Part of the Cervical Carcinogenesis Mechanisms.

Simple SummaryCervical cancer is one of the most lethal types of cancer in women from developing countries. These tumors are caused by long term infection with some human papillomavirus (HPV) types. Commonly, cervical cancer precursor lesions express high levels of matrix metalloproteinases. These enzymes break down specific components of the extracellular matrix affecting tissue structure and stiffness and cell motility. Matrix metalloproteinases and their natural inhibitors, such as Reversion-inducing Cysteine-rich protein with Kazal motifs (RECK) protein, are important in normal tissue maintenance and remodeling and play a major role in the transformation process. Here, we showed that RECK over expression reduced the tumorigenic capacity of cervical cancer cells in vivo. In addition, tumors over expressing RECK presented altered inflammatory infiltrating cells when compared to controls. Our findings are useful to further understand the biology of cervical cancer and can help to determine if RECK may be a good therapeutic target for cervical cancer treatment in the future.Human papillomavirus (HPV)-induced carcinogenesis comprises alterations in the expression and activity of matrix metalloproteinases (MMP) and their regulators. Reversion-inducing Cysteine-rich protein with Kazal motifs (RECK) inhibits the activation of specific metalloproteinases and its expression is frequently lost in human cancers. Here we analyzed the role of RECK in cervical carcinogenesis. Cervical cancer derived cell lines over expressing RECK were used to determine tumor kinetics as well as, cellular, immune and molecular properties in vivo. Besides, we analyzed RECK expression in cervical cancer samples. RECK over expression (RECK+) delayed tumor growth and increased overall survival in vivo. RECK+ tumors displayed an increase in lymphoid-like inflammatory infiltrating cells, reduced number and viability of tumor and endothelial cells and lower collagenase activity. RECK+ tumors exhibited an enrichment of cell adhesion processes both in the mouse model and cervical cancer clinical samples. Finally, we found that lower RECK mRNA levels were associated with cervical lesions progression and worse response to chemotherapy in cervical cancer patients. Altogether, we show that increased RECK expression reduced the tumorigenic potential of HPV-transformed cells both in vitro and in vivo, and that RECK down regulation is a consistent and clinically relevant event in the natural history of cervical cancer.

Laboratorio molecular en virus del papiloma humano (VPH) y cáncer

No hace muchos años la aproximación hacia las neoplasias malignas en seres humanos tenía un enfoque diagnóstico principalmente basado en los hallazgos morfológicos, y aunque teníamos conocimiento de la oncogénesis por virus desde hace casi medio siglo, este conocimiento no se había logrado integrar al diagnóstico, prevención y manejo oncológico [1]. En la década de los cincuenta, el entendimiento de la historia natural del cáncer de cuello uterino, con tiempos largos de evolución, permitió la implementación de protocolos de tamización, que hasta hace menos de una década, estaban basados en citologías cervicovaginales seriadas y regulares [2,3], sin mucho protagonismo en los algoritmos diagnósticos de la detección de variantes de alto riesgo del virus del papiloma humano (VPHAR) [4]. A pesar de que las pruebas moleculares se encuentran aprobadas para uso clínico desde aproximadamente el año 2001 [5], solo hasta el 2014 en paísescomo Estados Unidos, se incorporó la detección de genotipos de VPH-AR como prueba de tamización principal, que determina la necesidad de estudios adicionales para la detección temprana del cáncer cervicouterino [6].

Modeling the Balance of Benefits and Harms of Cervical Cancer Screening with Cytology and Human Papillomavirus Testing.

Benefits of screening should outweigh its potential harms. We compared various metrics to assess the balance of benefits and harms of cervical cancer screening. We used a cervical cancer natural history Markov model calibrated to the Canadian context to simulate 100,000 unvaccinated women over a lifetime of screening with either cytology every 3 years or human papillomavirus (HPV) testing every 5 years. We estimated the balance of benefits and harms attributable to screening using various metrics, including colposcopies/life-year gained, and net lifetime quality-adjusted life-years (QALY) gained, a measure integrating women's health preferences. We present the average (minimum-maximum) model predictions. Cytology-based screening led to 1,319,854 screening tests, 30,395 colposcopies, 13,504 life-years gained over a lifetime, 98 screening tests/life-year gained, 2.3 (1.6-3.3) colposcopies/life-year gained, and a net lifetime gain of 10,735 QALY (5,040-17,797). HPV-based screening with cytology triage in the same population would lead to 698,250 screening tests, 73,296 colposcopies, 15,066 life-years gained over a lifetime, 46 screening tests/life-year gained, 4.9 colposcopies/life-year gained (2.9-11.1), and a net lifetime gain of 11,690 QALY (4,409-18,742). HPV-based screening was predicted to prevent more cancers, but also incur more screening harms than cytology-based screening. Metrics using colposcopies as the main harm outcome favored cytology-based screening, whereas metrics based on screening tests and health preferences tended to favor HPV-based screening strategies. Whether HPV-based screening will improve the balance between benefits and harms of cervical cancer screening depends on how the balance between benefits and harms is assessed.

Are uninsured women in a national screening program having longer intervals between cervical cancer screening tests?

With increased understanding of the natural history of cervical cancer, cervical cancer screening recommendations have evolved (Schiffman & Wentzensen, 2013). As research better quantified the balance of benefits and harms of screening, new recommendations called for longer intervals between screening tests. Adherence to longer screening intervals detects similar numbers of abnormalities and decreases harms associated with overscreening/overtreatment. In this descriptive study, we examined the cervical cancer screening intervals from 2010 to 2018 in the National Breast and Cervical Cancer Early Detection Program (NBCCEDP). There were 1,397,899 women aged 21–64 who were screened for cervical cancer from 2010 to 2018 and 556,743 rescreenings of average risk women were performed. The median cervical screening interval increased from 2.02 years in 2010 to 3.88 years in 2018. Providers serving uninsured women in a national screening program are following the recommendations of longer intervals between cervical cancer screenings.

Molecular detection of oncogenic subtypes of human papillomavirus (HPV) in a group of women in the Amazon region of Brazil

The natural history of cervical cancer is strongly related to the presence of human papillomavirus (HPV) infection, with its relationship with cervical cancer being a matter of concern. It is estimated that 70% of all cervical cancers worldwide are caused by HPV 16 and 18. Accordingly, the present study aimed to contribute to the identification of HPV subtypes circulating in a group of women of Manaus-Brazil. Cervical samples were collected from 49 women, following the eligibility criteria of the study, and DNA was then extracted from the samples, which were analyzed for the presence of the virus in the genetic material through the polymerase chain reaction (PCR) using generic primers (GP05/06). Finally, identification of the viral subtypes was performed using specific primers for the detection of the main subtypes already examined (16 and 18). Positive HPV DNA was detected in 100% of the samples included in the study. Human papillomavirus 16 was the most prevalent subtype in the majority of lesions, accounting for 29 (59.2%) of the positive cases, and HPV 18 was detected in four (8.2%) women. In these 4 cases there was co-infection, with the presence of both HPV 18 and HPV 16. Therefore, 40.8% (20 cases) in which HPV DNA was detected presented infection with other subtypes of HPV not included in the study. This data has clinical implications related to cervical cancer prevention, as the current prophylactic HPV vaccines are only effective against high-risk HPV 16 and 18 subtypes.

Economic evaluation of HPV DNA test as primary screening method for cervical cancer: A health policy discussion in Greece.

BackgroundHPV test appears to be more effective in cervical cancer (CC) screening. However, the decision of its adoption as a primary screening method by substituting the established cytology lies in the evaluation of multiple criteria. Aim of this study is to evaluate the economic and clinical impact of HPV test as primary screening method for CC.MethodsA decision tree and a Markov model were developed to simulate the screening algorithm and the natural history of CC. Fourteen different screening strategies were evaluated, for women 25–65 years old. Clinical inputs were drawn from the HERMES study and cost inputs from the official price lists. In the absence of CC treatment cost data, the respective Spanish costs were used after being converted to 2017 Greek values. One-way and probabilistic sensitivity analyses were conducted.ResultsAll screening strategies, that offer as primary screening method triennial HPV genotyping (simultaneous or reflex) alone or as co-testing with cytology appear to be more effective than all other strategies, with regards to both annual CC mortality, due to missed disease (-10.1), and CC incidence(-7.5) versus annual cytology (current practice). Of those, the strategy with HPV test with simultaneous 16/18 genotyping is the strategy that provides savings of 1.050 million euros annually. However, when the above strategy is offered quinquennially despite the fact that outcomes are decreased it remains more effective than current practice (-7.7 deaths and -1.3 incidence) and more savings per death averted (1.323 million) or incidence reduced (7.837 million) are realized.ConclusionsHPV 16/18 genotyping as a primary screening method for CC appears to be one of the most effective strategies and dominates current practice in respect to both cost and outcomes. Even when compared with all other strategies, the outcomes that it generates justify the cost that it requires, representing a good value for money alternative.

Building research capacity through programme development and research implementation in resource-limited settings - the Ipabalele study protocol: observational cohort studies determining the effect of HIV on the natural history of cervical cancer in Botswana

IntroductionThe global burden of cancer continues to increase in low- and middle-income countries, particularly in sub-Saharan Africa (SSA). Botswana, a middle-income country in SSA, has the second highest prevalence of...

Evaluation of additional benefits of HPV vaccination to cervical cancer screening in France

Abstract Background The National Cancer Institute (INCa) undertook the evaluation of the expected impact of HPV vaccination in the context of the recent marketing of nonavalent vaccine (Gardasil®9) and the implementation of organized screening (OS) of cervical cancer (CC) in France. Methods The study is based on a microsimulation model that replicates the natural history of CC. A cohort of 14-year-old women is generated and followed until death. Others HPV-infection related diseases (condyloma, anal cancer, penile cancer and oropharynx cancer) are not modelled. Different strategies were compared with the current vaccination coverage rate (VCR) of 21.4% (2017): impact of increased VCR alone and increased VCR combined with correction of inequalities (CI). Results are presented according to two hypotheses for the duration of protection offered by the vaccine (limited to 20 years and lifelong) and according to two hypotheses for price of the vaccine (French price and average European prices). Results The incremental cost-effectiveness ratio (ICER) was less than 15 000 euros per QALY (quality-adjusted life year) in all the assessed strategies. For each 14-year-old women cohort, 85% VCR with CI would prevent at least: 2 546 conations, 2 347 precancerous lesions CIN 2 / 3 diagnosed, 377 CCs, 139 deaths per CC (20 years vaccine protection). Scenarios based on increasing VCR with CI are the most cost-effective. Conclusions The study quantifies the increased risk of CC-related outcomes associated with current sub-optimal VCR and the possible investment to implement actions in order to improve the efficiency of the current strategies and tackle health inequalities (communication campaign, actions toward underserved women). Key messages Improving HPV vaccination uptake is a cost-effective measure, even considering only the cervical cancer prevention. Including health inequalities participation in modeling is crucial as underserved women are both less vaccinated and screened.