[Recurrent respiratory papillomatosis]. / Papillomatose respiratoire récurrente.

Recurrent respiratory papillomatosis is a chronic infection of the airway mucosa by the human papilloma virus, in the form of recurrent exophytic papilloma. Two clinical forms are distinguished: juvenile and adult onset. Depending on their size and location, papilloma can cause dysphonia, pharyngeal discomfort, until obstruction of the airway. There is no curative treatment. The management strategy is to surgically remove symptomatic disease by transoral approach, but some recurrent disease require multiple interventions and -adjuvant therapies. The symptoms caused by the disease as well as treatments' side effects have a major impact on patient's quality of life. Vaccination against HPV currently represents the best strategy to prevent disease.

La papillomatose respiratoire récurrente est une infection chronique de la muqueuse des voies aériennes par le virus du papillome humain sous forme de papillomes exophytiques récidivants. Deux formes cliniques sont décrites : juvénile et adulte. Selon leurs taille et localisation, les papillomes peuvent être responsables d'une dysphonie, d'une gêne pharyngée, jusqu'à l'obstruction des voies respiratoires. Il n'y a pas de traitement curatif définitif. La stratégie est chirurgicale par l'ablation des lésions symptomatiques par voie endoscopique, mais certaines maladies récidivantes nécessitent de multiples interventions en plus des thérapies adjuvantes. L'impact sur la qualité de vie est majeur, à travers les symptômes occasionnés et les séquelles des traitements. La vaccination représente le meilleur espoir d'éradication de la maladie.

Comparison of cervical cancer screening models based on Pap and HPV tests in Tbilisi, Georgia.

OBJECTIVE: The objective of this study was to evaluate the effectiveness of human papillomavirus HPV test with HPV16/18 genotyping and liquid-based cytology (LBC) triage as a primary screening method for cervical cancer compared to conventional Pap test in women undergoing routine cervical cancer screening in Tbilisi. METHODS: Cross-sectional, prospective study was conducted, where 1,000 enrolled women aged 30-60 years during one visit underwent conventional Pap smear and Hr-HPV testing (Roche Cobas system). Women with any positive screening results were referred for further evaluation and remaining cells from the Cell Collection Medium vial were used for LBC. The study calculated sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) for each screening method and receiver-operating characteristic (ROC) curve to evaluate the accuracy of each diagnostic method in identifying people with CIN2+ diseases. RESULTS: The HPV test with HPV16/18 genotyping and LBC triage demonstrated higher sensitivity (76.9%), specificity (71.6%), and PPV (34.5%) compared to conventional Pap tests (p < 0.05). NPV was also high with the HPV test (94.1%). The HPV test alone had the highest sensitivity (92.3%) and NPV (96.7%), but lower specificity (41.4%) and PPV (22.6%) than the HPV test with HPV16/18 genotyping and LBC triage (p < 0.05). Comparing the areas under the curve (AUCs), only the HPV with HPV16/18 genotyping and LBC triage showed a statistically significant difference when compared to conventional Pap (0.71 vs. 0.55, p = 0.03) and high figures of AUC 0.71 (95% CI: 0.58-0.85) suggesting that HPV test with HPV16/18 genotyping and LBC triage is a more reliable screening method for detecting CIN2+ disease and preventing cervical cancer, than other screening modality. CONCLUSION: The results suggest that the HPV test with HPV16/18 genotyping and LBC triage is a more effective primary screening method compared to conventional Pap tests. This information should be the basis for transition from cytological screening to HPV testing in Georgia.

Molecular detection of high-risk papillomaviruses and vaccination status in normal cytology in Congo.

OBJECTIVE: The aim of this study was to identify the molecular prevalence of high-risk HPV infection and the distribution of genotypes present in normal cytology, as well as to determine the vaccination status of our study population. METHODS: 110 cervical samples were taken from individuals, and 1 ml of each sample was added to the Xpert HPV cartridge in the sample compartment before it was placed in the Cepheid GeneXpert system. Detection was performed simultaneously via amplification of the E6 and E7 genes in five fluorescent channels (HPV16, HPV18/45, HPV31/33/35/52/58, HPV51/59, and HPV39/56/66/68a). RESULTS: 36/110 (33%) of all samples tested were positive for HPV DNA. The predominant genotypes were HPV16 (12.7%) and other pooled HR-HPV types (8.2%). All women who received the Gardasil-9 vaccine (3.6%) had HPV, and infection was associated with travel outside Africa. 96.4% of the screened individuals had not received any HPV vaccine. CONCLUSION: Our research confirms a widespread HR-HPV infection in our population and extends the importance of studies on the molecular prevalence of HPV, particularly in women with normal cytology and apparent good health, in view of the cruel lack of public awareness of HPV infections.

Diagnostic and prognostic potential of the intra-tumoral microbiota profile in HPV-independent endocervical adenocarcinoma.

Background: Microbial community dynamics have been involved in numerous diseases, including cancer. The diversity of intertumoral microbiota in human papillomavirus independent endocervical adenocarcinoma (HPVI ECA) is not well-characterized. Objective: Our objective is to delineate the intratumoral microbiota profile in HPVI ECA and investigate its potential influence on oncogenesis. Methods: We analyzed 45 HPVI ECA cases, comprising 36 gastric-type ECA (GEA) and 9 clear cell carcinomas (CCC). We compared the microbial composition within cancerous and adjacent noncancerous tissue samples using 5R-16S ribosomal DNA sequencing. Further, we investigated the correlation between specific microbes and clinical-pathological metrics as well as patient outcomes. Results: Our findings demonstrate notable differences in the microbial spectra between cancerous and adjacent noncancerous tissues. Amongst HPVI ECA subtypes, GEAs exhibit more microbial variations compared to CCCs. Using the Random Forest algorithm, we identified two distinct microbial signatures that could act as predictive biomarkers for HPVI ECA and differentiate between GEA and CCC. Varied microbial abundances was related to clinical characteristics of HPVI ECA patients. In addition, high levels of Micrococcus and low levels of unknown genus75 from the Comamonadaceae family were associated with poorer outcomes in HPVI ECA patients. Similarly, an abundance of Microbacterium correlated with reduced overall survival (OS), and a high presence of Streptococcaceae family microbes was linked to reduced recurrence-free survival (RFS) in GEA patients. Intriguingly, a high abundance of Micrococcus was also associated with a worse OS in GEA patients. Conclusion: The study reveals distinct microbial signatures in HPVI ECA, which have potential as biomarkers for disease prognosis. The correlation between these tumor-associated microbiota features and clinicopathological characteristics underscores the possibility of microbiome-based interventions. Our research provides a foundation for more in-depth studies into the cervical microbiome's role in HPVI ECA.

Age-specific performance of human papillomavirus E6/E7 mRNA assay versus cytology for primary cervical cancer screening and triage: community-based screening in China.

Background: In the general population, primary human papillomavirus (HPV) testing is advocated for cervical cancer (CC) screening. HPV E6/E7 mRNA (Aptima HPV, AHPV) assays have garnered considerable traction due to their higher specificity when compared with HPV DNA assays. Here, we investigated age-specific primary AHPV screening assays and different triage strategies versus cytology to identify the best approach. Methods: Between April 2018 and December 2021, we recruited female participants from 34 communities across Liaoning province and Qingdao City, China. Primary cervical screening protocols included liquid-based cytology (LBC) and AHPV assays, with females positive for any assays undergoing colposcopy. Genotyping (AHPV-GT) was conducted on all HPV-positive samples. Our primary outcomes were the identification of age-specific detection rates, colposcopy referral rates, and sensitivity and specificity values for high-grade squamous intraepithelial lesions or worse (HSIL+). AHPV and different triage strategy performances were also examined across different age cohorts. Results: Our investigation included 9911 eligible females. Age-specific abnormal cytology rates were in the 6.1%-8.0% range, and were highest in 45-54-year olds. When compared with 35-44-or 45-54-year olds, HPV prevalence was highest in 55-64-year olds (12.2% or 11.6% vs.14.1%, P = 0.048 and P = 0.002, respectively). In 35-44-year olds, AHPV sensitivity for detecting HSIL+ was 96.6 (95% confidence interval [CI]: 89.7-100) - significantly higher than LBC sensitivity (65.5 [95% CI: 48.3-82.8], P < 0.001). When compared with LBC, HSIL+ detection rates by AHPV-GT using reflex LBC triage increased by 31.5% (9.6‰ vs. 7.3‰), and colposcopy referral rates decreased by 16.4% (5.1% vs. 6.1%). In 45-54-year olds, HSIL+ detection rates for AHPV-GT using reflex LBC triage were lower than LBC rates (6.2‰ vs. 6.6‰). In 55-64-year olds, AHPV sensitivity (97.2 [95% CI: 91.7-100.0]) was higher than LBC sensitivity (66.7 [95% CI: 50.0-80.6], P = 0.003). The area under the curve (AUC) value was not significantly different between AHPV-GT with reflex LBC triage and LBC (0.845 [95% CI: 0.771-0.920] vs. 0.812 [95% CI: 0.734-0.891], P = 0.236). Conclusions: Primary AHPV screening using different triage strategies were different across different age cohorts. Thus, AHPV may be an appropriate primary screening method for 35-44 and 55-64 year old females, while AHPV-GT with reflex LBC triage may be more apt for 35-44 year old females.

HPV self-collection for cervical cancer screening among survivors of sexual trauma: a qualitative study.

Intimate partner violence affects 20-30% of women in the United States. Disparities in routine cervical cancer surveillance have been demonstrated in certain populations, including victims of intimate partner violence (IPV). This study examined and assessed the acceptability of high-risk HPV (hrHPV) self-collection among individuals who have experienced IPV. We conducted an observational study using qualitative data collection and analysis. We interviewed individuals with a history of IPV and who currently reside in Oregon. This study identified key themes describing knowledge and attitudes towards cervical cancer screening for individuals who have experienced IPV. They include: guideline knowledge, prior office-based cervical cancer screening experience, barriers to cervical cancer screening, at-home hrHPV self-collection experience, and testing confidence. Participants experienced fewer barriers and expressed increased comfort and control with hrHPV self-collection process. Individuals with a history of IPV have lower rates of cervical cancer screening adherence and higher rates of cervical dysplasia and cancer than other populations. The patient-centered approach of hrHPV self-collection for cervical cancer screening can reduce barriers related to the pelvic exam and empower patients to reduce their risks of developing cervical cancer by enabling greater control of the testing process.

Criteria for second generation comparator tests in validation of novel HPV DNA tests for use in cervical cancer screening.

While HC2 and GP5+/6+ PCR-EIA were pivotal in test validation of new HPV assays, they represent the first generation of comparator tests based upon technologies that are not in widespread use anymore. In the current guideline, criteria for second-generation comparator tests are presented that include more detailed resolution of HPV genotypes. Second-generation comparator tests should preferentially target only the 12 genotypes classified as carcinogenic (IARC-group I), and show consistent non-inferior sensitivity for CIN2+ and CIN3+ and specificity for ≤CIN1 compared to one of the first-generations comparators, in at least three validation studies using benchmarks of 0.95 for relative sensitivity and 0.98 for relative specificity. Validation should take into account used storage media and other sample handling procedures. Meta-analyses were conducted to identify the assays that fulfill these stringent criteria. Four tests fulfilled the new criteria: (1) RealTime High-Risk HPV Test (Abbott), (2) Cobas-4800 HPV test (Roche Molecular System), (3) Onclarity HPV Assay (BD Diagnostics), and (4) Anyplex II HPV HR Detection (Seegene), each evaluated in three to six studies. Whereas the four assays target 14 carcinogenic genotypes, the first two identify separately HPV16 and 18, the third assay identifies five types separately and the fourth identifies all the types separately.

Transition from opportunistic cytological to organized screening program with DNA-HPV testing detected prevalent cervical cancers 10 years in advance.

Cervical cancer screening in Brazil is opportunistic, based on cytology and offered for women aged 25-64 years, with low coverage (30%) and 70% of cancer diagnoses done in advanced stages, without impact on mortality. The current study reports 5-year first-round results of a population-based DNA-HPV testing screening program in a Brazilian city, which intended to be a model for transition to a more efficient program. Program flowchart is simple and current, indicating repetition of a negative test after five years. The first-round (October 2017-September 2022) screened 20,551 women by DNA-HPV testing with 58.7% coverage and 99.4% compliance with the program's targeted age range. Coverage increases to 77.8% when excluding the 'pandemic period'. The DNA-HPV testing was 87.2% negative with 6.2% colposcopy referrals and 84.8% colposcopies performed. A total of 258 high-grade precursor lesions and 29 cervical cancers (mean age = 41.4 years, 83% Stage I) were detected. As a reference, 41,387 cytology tests from the previous program (2012-2016) detected 36 cervical cancers (mean age = 52.0 years, p = 0.0005), with 67% in advanced stages (p < 0.0001). Organizing cervical cancer screening using DNA-HPV testing demonstrated good coverage, high age and colposcopy compliance, and detection of more precancerous lesions and cervical cancers 10 years in advance.

Comment on: Effect of Pap Smear Cytology, HPV Genotyping On the Concordance of Colposcopy and Conization Results.

Null.

HPV self-sampling implementation strategies to engage under screened communities in cervical cancer screening: a scoping review to inform screening programs.

Introduction: Human papillomavirus (HPV) testing as a method of cervical cancer screening can be performed by healthcare providers or by patients through self-sampling directly in the community, removing several barriers experienced by under screened populations. The objective of this scoping review was to determine which HPV self-sampling implementation and engagement strategies have been used to engage under screened populations (i.e., Indigenous, newcomer, and rural and remote communities) in cervical cancer screening. Methods: A scoping review was conducted searching MEDLINE, CINAHL, EMBASE, Cochrane Library, and SocINDEX from inception to August 2023. The inclusion criteria were: (1) Indigenous, newcomer, and rural and remote communities; (2) countries identified as members of the Organization for Economic Co-operation and Development; and (3) intervention included HPV self-sampling. The review was registered prior to conducting the search (https://osf.io/zfvp9). Results: A total of 26 studies out of 2,741 studies met the inclusion criteria. In-person engagement with trusted community leaders was the most widely used and accepted recruitment and engagement strategy across all three populations. Six out of seven studies with Indigenous communities distributed HPV self-sampling kits to eligible participants in person in a clinical setting for collection on site or at home. Similarly, nine of the identified studies that engaged newcomers recruited participants in person through the community, where eligible participants were either given a kit (n = 7) or received one in the mail (n = 2). Lastly, of the 10 identified studies engaging rural and remote participants in HPV self-sampling, six recruited eligible participants in person at various community locations and four used electronic medical records or registries to identify and mail kits to participants. Discussion: HPV self-sampling through in person kit distribution and mail out of HPV self-sampling kits is an effective way to increase participation rates amongst under screened populations.

Self-Screening for Cervical Cancer Offered through a Digital Platform in a Region of British Columbia with Lower Screening Rates.

Cervical cancer is highly preventable through vaccination, early detection, and treatment, yet is the fourth most common cancer globally. HPV testing is superior to cytology for the detection of cervical pre-cancer, and jurisdictions around the world are implementing HPV primary screening, which offers the opportunity for self-screening, an important self-care intervention. Digital health solutions are also increasingly important components of self-care. In this study, we assessed the acceptability and completion of self-screening for cervical cancer offered through a digital platform within a low screening uptake region of British Columbia. The primary objective of this study was to evaluate the acceptability of self-screening for cervical cancer offered through a digital platform as measured by return rates of self-screening kits. Patients due or overdue for cervix screening were invited to participate. Eligible participants registered online to receive a self-screening kit, which included a device for vaginal self-screening, instructions, and a return envelope, sent to their home. After self-screening using the vaginal device, HPV testing was conducted. HPV-negative participants were returned to routine screening, and HPV-positive participants were recommended for cytology or colposcopy. Attendance rates at follow-up were evaluated. Participants were invited to complete an acceptability survey. From April 2019 to December 2023, 283 participants were sent kits, with 207 kits returned for a completion rate of 73%. Of valid samples (n = 202), 15 were HPV positive, and 93% attended follow-up care. Most respondents found the CervixCheck website easy to use, informative, and secure and were satisfied with receiving their results online. CervixCheck had a high completion rate among participants who were sent a self-screening kit. High compliance with recommended follow-up and high acceptability of self-screening for cervical cancer was observed. Most participants indicated they would self-screen again in the future. Innovative approaches to cervical screening, including self-screening and the use of digital health interventions, are ways to enhance equity and improve uptake of cervical screening.

Human Papillomavirus, Cervical Intraepithelial Neoplasia, and Quantitative Blood Loss at Delivery.

Studies using estimated blood loss show the association of either human papillomavirus (HPV) or cervical intraepithelial neoplasia (CIN) with postpartum hemorrhage (PPH). We study the association of HPV or CIN with either blood loss or PPH as measured by the more precise measure of quantitative blood loss (QBL). We retrospectively studied 2,334 peripartum women with a documented Pap smear prior to de- livery. The main predictor variable had categories for HPV and CIN as compared to normal cytology. Covariates included demographics, medical/surgical history, and pregnancy variables. Model 1 included the whole sample. Model 2 included only those with an operative vaginal delivery or a cesarean delivery. Outcome measures were QBL and PPH measured by QBL. We found in model 1 that those HPV positive and those with CIN were each not significantly associated with QBL. In model 2, those HPV positive were significantly associated with increased QBL (B = 0.11, SE = 0.05, p = 0.047), while CIN was not significantly associated with QBL. In model 1, those HPV positive and those with CIN were each not significantly associated with PPH. In model 2, those HPV positive were significantly associated with increased odds for PPH (OR:11.03, 9% CI:1.77, 68.74, p = 0.01) while CIN was not significantly associated with PPH. In conclusion, the presence of HPV was positively associated with an increase in the QBL and PPH at time of delivery for those with operative vaginal and cesarean deliveries. We suggest that clinicians take HPV results of Pap smears into consideration when considering a patient's risk of PPH.

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

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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.

Human papillomavirus self-sampling and urine-sampling tests and the management and short-term outcomes of cervical intraepithelial neoplasia: A prospective observational study.

AIM: The importance of human papillomavirus (HPV) co-testing using physician-, self-, and urine-collected samples to predict cervical intraepithelial neoplasia (CIN) grade 1-2 prognoses has not been previously reported. Therefore, this study aimed to investigate outcomes of patients with CIN 1-2 who simultaneously underwent physician-, self-, and urine-collection sampling tests. METHODS: This study was conducted in Japan between October 2019 and November 2022 and examined the proportion of cases with CIN 1-2 progressions, the percentage of cases with persistent CIN 1-2, and the outcome differences according to the results of physician-, self-, and urine-sampling tests. RESULTS: There were 105 and 59 CIN 1 and 2 cases, respectively, with progression or persistence in 27 (29.3%) and 21 (50.0%) cases, respectively. The median follow-up was 20 and 12 months, respectively. Progression and persistence of CIN 1 were significantly associated with HPV-positive physician- and self-collected samples. No significant difference was observed between cases with CIN 2 who had HPV-positive and HPV-negative results using any sampling method. CONCLUSIONS: Physician- and self-testing for HPV are crucial for predicting disease progression risk in CIN 1 cases. Future research with an extended observation period and consideration of the progression risks is warranted.

Clinical validation of the Roche cobas HPV test on the Roche cobas 5800 system for the purpose of cervical screening.

This study assessed the relative clinical sensitivity and specificity, as well as reproducibility, for high-risk HPV types of the Roche cobas HPV test when processed using the Roche cobas 5800 system. The results from this study demonstrate that the cobas HPV test using the cobas 5800 system fulfils the Meijer criteria for use in population-based cervical screening. This clinical validation study also examines the clinical sensitivity and specificity based on partial genotyping, with separate detection of HPV16 and HPV18, compared with the Roche cobas 4800 HPV test, a second-generation standard comparator assay. The cobas HPV test has a relative clinical sensitivity of 1.000, when compared with the cobas 4800 HPV test to detect histologically confirmed CIN2+ lesions in woman aged 30 years or older, with a relative clinical specificity of 0.995. The general intra- and inter-laboratory agreement for the cobas HPV test on the cobas 5800 system for finding a HPV positive result were 99.1% and 99.6%, respectively.IMPORTANCEThis study demonstrates, for the first time, the clinical performance of the Roche cobas HPV test when processed using the new cobas 5800 system [cobas (5800)]. This study shows that the cobas (5800) demonstrates relative clinical sensitivity and specificity, when compared with a standard comparator HPV test, which meets the international HPV test validation requirements. Intra- and inter-laboratory reproducibility also fulfills these criteria. The current study demonstrates that the cobas (5800) can be used for primary HPV-based cervical screening on cervical specimens.

Hotspots of Anal Cancer Screening in a High-risk Population: A Clinical Study on Free Provision, Best Method, Self-sampling, and Independent Risk Factors.

BACKGROUND/AIM: As of 2024, anal cancer (AC) has been steadily increasing worldwide but, due to insufficient evidence, anal cancer screening (ACS) has yet to be standardized. Furthermore, most high-risk people in the world have no help paying for it. Therefore, our primary endpoint was to assess the best screening method for these subjects through a provision that was free of charge (all costs were covered by the Italian public health service). Awareness-raising campaign, determination of risk factors, education on anal self-examination, and sampling (ASS) were secondary objectives. PATIENTS AND METHODS: Screening was on a voluntary basis. Engaging in receptive anal intercourse and having a history of cervical dysplasia were the main inclusion criteria. Level 1 ACS tools included digital ano-rectal examination, anoscopy, anal Pap, and anal human papillomavirus (HPV) DNA test (both through self- and proctologist- sampling); high-resolution anoscopy (HRA) with (HRAB) or without biopsy comprised level 2 screening. High-risk people were enrolled until the available funds were exhausted. RESULTS: Fifty high-risk people (40 men who had sex with men -MSM-, 9 women, and 1 heterosexual man) were enrolled. AC was found in one HIV-seropositive MSM, high-grade squamous intraepithelial lesion in 10 (20%) MSM, low-grade squamous intraepithelial lesion LSIL in 13 cases (12 MSM and 1 woman). The combination of HRAB and Pap smear screening achieved the highest values for sensitivity, specificity, and accuracy. ASS HPV DNA test provided excellent results comparable to clinician retrieval. Overweight and college education were identified as independent factors for the risk of and prevention of AC, respectively. CONCLUSION: A free ACS not only appears justified but also recommended to people screened for AC. Excess weight represents a further risk for this population.

Invitation strategy of vaginal HPV self-sampling to improve participation in cervical cancer screening: a systematic review and meta-analysis of randomized trials.

BACKGROUND: Human papillomavirus (HPV) self-sampling is recognized as a feasible option for enhancing screening for cervical cancer, particularly among hard-to-reach women. The magnitude of the effectiveness of screening participation under different invitation strategies was reported. This review seeks to compare the effectiveness of invitation strategies in increasing screening participation of HPV self-sampling across diverse study settings. METHODS: A systematic literature search was conducted in Embase, MEDLINE, and PubMed in April 2023. Articles were included if (1) their target participants were aged between 25 and 70 years; (2) participants in the intervention arm were randomized to receive HPV self-sampling devices through various invitation strategies; (3) participants in the control arm who either received invitations for cervical cancer screening other than HPV self-sampling or opportunistic screening as usual care; (4) studies that provided sufficient data on screening participation in HPV self-sampling as outcome measured. The study design of the included articles was limited to randomized controlled trials. RESULTS: A total of 15 articles were included in this review. Invitation strategies of disseminating HPV self-sampling devices included opt-out and opt-in. Meta-analysis revealed screening participation in the self-sampling group was significantly greater than control arm (OR 3.43, 95% CI 1.59-7.38), irrespective of the invitation strategy employed. Among invitation strategies, opt-out appeared to be more effective on increasing screening participation, compared to control and opt-in strategy (opt-out vs. control OR 3.91, 95% CI 1.82-8.42; opt-in vs. control OR 1.34, 95% CI 0.28-6.39). CONCLUSIONS: Opt-out strategy is more successful at improving screening participation compared to opt-in and routine invitation to cervical screening. It is therefore a promising way to improve participation in cervical cancer screening. The findings of this review provide important inputs to optimize strategies for inviting women to participate in vaginal HPV self-sampling across the study setting, thus improving participation in cervical cancer screening.

RAP1-GTPase immunostaining is altered in human precancerous and cancerous cervical lesions.

Aim: This study investigated RAP1 immunostaining variation in different cell types during CC progression.Methods: Paraffin-embedded cervical tissues from 101 patients were categorized into control, pre-neoplastic and neoplastic groups. RAP1 immunolocalization, HPV detection and genotyping were performed. A semiquantitative immunoreactive score was employed to compare labeling intensity, cellular localization, nuclear labeling, percentage and distribution of reactive cells.Results: 73% (72/99) of cervical specimens were HPV+. RAP1 was localized in the nucleus and cytoplasm of all samples. Cytoplasmic RAP1 immunoscore was higher than nuclear score in all CC groups. RAP1 intensity increased with lesion severity. SCC samples exhibited predominantly intense RAP1 immunostaining.Conclusion: RAP1 is an efficient biomarker for detecting invasive CC lesions but has limited utility in distinguishing SCC grades.

[Box: see text].

Early evaluation of a screen-and-treat strategy using high-risk HPV testing for Uganda: Implications for screening coverage and treatment.

Background: Uganda has a high burden of cervical cancer and its current coverage of screening based on visual inspection with acetic acid (VIA) is low. High-risk HPV (hrHPV) testing is recommended by the World Health Organization as part of the global elimination strategy for cervical cancer. In this context, country-specific health economic evaluations can inform national-level decisions regarding implementation. We evaluated the recommended hrHPV screen-and-treat strategy to determine the minimum required levels of coverage and treatment adherence, as well as the maximum price level per test, for the strategy to be cost-effective in Uganda. Methods: We conducted a headroom analysis to estimate potential room for spending on implementing the hrHPV screen-and-treat strategy at different levels of coverage and treatment adherence (from 10% to 100%) at each screening round, and at different price levels of the hrHPV test. We compared the strategy with the existing VIA-based screen-and-treat policy in Uganda. We calculated headroom as the product of number of life years gained by the strategy and the willingness-to-pay threshold, minus the incremental costs incurred by the strategy. Positive headroom was interpreted as an indication of cost-effectiveness. Results: Compared with VIA-based screening with low 5% coverage, the hrHPV screen-and-treat strategy required at least 30% coverage and adherence for positive mean headroom, and compared with 30% VIA-based screening coverage, the minimum levels were 60%. At 60% coverage and adherence, the maximum acceptable price per hrHPV test was found to be between 15 and 30 international dollars. Conclusions: The hrHPV-based screen-and-treat strategy could be cost-effective in Uganda if the screening coverage and treatment adherence are at least 30% in each screening round, and if the price per test is set below 30 international dollars. The minimum required levels of screening coverage and adherence to treatment provide potential starting points for decision-makers in planning the rollout of hrHPV testing. The headroom estimates can guide the planning costs of screening infrastructure and campaigns to achieve the required coverage and treatment adherence in Uganda.