Effectiveness of self-sampling human papillomavirus test on precancer detection and screening uptake in Japan: The ACCESS randomized controlled trial.

Japan is lagging in cervical cancer prevention. The effectiveness of a self-sampling human papillomavirus (HPV) test, a possible measure to overcome this situation, has not yet been evaluated. A randomized controlled trial was performed to evaluate the effectiveness of a self-sampling HPV test on detection of cervical intraepithelial neoplasia grade 2 or worse (CIN2+) and screening uptake. Women between 30 and 58 years old who did not participate in the cervical cancer screening program for ≥3 years were eligible and assigned to the intervention group (cytology or self-sampling HPV test) or control group (cytology). Participants assigned to the intervention group were sent a self-sampling kit according to their ordering (opt-in strategy). A total of 7337 and 7772 women were assigned to the intervention and control groups, respectively. Screening uptake in the intervention group was significantly higher than that in the control group (20.0% vs. 6.4%; risk ratio: 3.10; 95% confidence interval [CI]: 2.82, 3.42). The compliance rate with cytology triage for HPV-positive women was 46.8% (95% CI: 35.5%, 58.4%). CIN2+ was detected in five and four participants in the intervention and control groups, respectively; there was no difference for intention-to-screen analysis (risk ratio: 1.32; 95% CI: 0.36, 4.93). Self-sampling of HPV test increased screening uptake; however, no difference was observed in the detection of CIN2+, probably due to the low compliance rate for cytology triage in HPV-positive women. Efforts to increase cytology triage are essential to maximize precancer detections.

Comparative performance of various human papillomavirus assays available in Korea for detecting cervical intraepithelial neoplasia.

AIM: The aim of this study was to evaluate the clinical performance for detecting cervical intraepithelial neoplasia (CIN) 2 or higher lesions among available human papillomavirus infection (HPV) genotyping tests in Korea. METHODS: Eligible patients visited 13 tertiary hospitals for colposcopic biopsy following cervical cytology and HPV genotyping test between January and December 2018. Baseline characteristics including age, body mass index (BMI), and parity were collected from 3798 patients. The performance of the Roche Cobas HPV 4800 was evaluated against other domestic HPV assays to detect CIN2 or higher. RESULTS: A total of seven types of HPV genotyping tests were analyzed in the research institutes. A total of 1358 patients (35.8%) tested Anyplex II HPV 28 and 701 patients (18.5%) tested Cobas 4800 HPV. The overall sensitivity in the detection of CIN2 or higher was 41.5% (38.9-44.1) in patients positive for HPV 16/18. The Cobas test for HPV 16/18 was concordant with other assays evaluated for detection of CIN2 or higher and showed sensitivity of 46.6%, which was not significantly different from other assays. Although Anyplex II HPV28 (Seegene) showed slightly decreased sensitivity for detecting CIN2 or higher lesion with HPV 16/18 positive (39.8%, p < 0.05) compared to Cobas 4800, in aspect of high-risk HPV positive, Anyplex II HPV28 showed increased sensitivity (96.9%, p < 0.05). CONCLUSION: The performance of the HPV genotype test that were commonly used in Korea was concordant with Cobas HPV test. Further studies are needed to evaluate the safety, efficiency, and cost-effectiveness of the various commercially available domestic HPV assays.

A proposed new generation of evidence-based microsimulation models to inform global control of cervical cancer.

Health decision models are the only available tools designed to consider the lifetime natural history of human papillomavirus (HPV) infection and pathogenesis of cervical cancer, and the estimated long-term impact of preventive interventions. Yet health decision modeling results are often considered a lesser form of scientific evidence due to the inherent needs to rely on imperfect data and make numerous assumptions and extrapolations regarding complex processes. We propose a new health decision modeling framework that de-emphasizes cytologic-colposcopic-histologic diagnoses due to their subjectivity and lack of reproducibility, relying instead on HPV type and duration of infection as the major determinants of subsequent transition probabilities. We posit that the new model health states (normal, carcinogenic HPV infection, precancer, cancer) and corollary transitions are universal, but that the probabilities of transitioning between states may vary by population. Evidence for this variability in host response to HPV infections can be inferred from HPV prevalence patterns in different regions across the lifespan, and might be linked to different average population levels of immunologic control of HPV infections. By prioritizing direct estimation of model transition probabilities from longitudinal data (and limiting reliance on model-fitting techniques that may propagate error when applied to multiple transitions), we aim to reduce the number of assumptions for greater transparency and reliability. We propose this new microsimulation model for critique and discussion, hoping to contribute to models that maximally inform efficient strategies towards global cervical cancer elimination.

Risk factors for type-specific persistence of high-risk human papillomavirus and residual/recurrent cervical intraepithelial neoplasia after surgical treatment.

OBJECTIVE: This study aimed to investigate the clinicopathologic risk factors for type-specific persistence of high-risk human papillomavirus (hrHPV) and residual/recurrent cervical intraepithelial neoplasia (CIN) after surgical treatment. METHODS: Patients with CIN-2/3 who underwent conization or loop electrosurgical excision procedure (LEEP) at Korea University Hospital were enrolled. All patients underwent hrHPV testing and genotyping before conization or LEEP followed by both hrHPV genotyping and cytology. The significance of associations between patient characteristics and persistence of infection were assessed by multivariate logistic regression analyses. RESULTS: Among 398 women with pathologically confirmed CIN-2/3, 154 (38.7%) patients showed hrHPV persistence after surgical treatment. In multivariate analysis, high preoperative hrHPV load (P<0.05; odds ratio [OR], 2.063), presence of CIN-2 at treatment (P<0.01; OR, 2.732), and multiple hrHPV infections (P<0.001; OR, 4.752) were associated with hrHPV persistence. HPV 53 was the most likely to persist after treatment (24/43, 55.8%). The risk of residual/recurrent CIN-2/3 was higher in persistent infection with HPV 16 than other types (P<0.05). Menopause (P<0.001; OR, 3.969), preoperative and postoperative hrHPV load (P<0.05; OR, 2.430; P<0.05; OR, 5.351), and infection with multiple hrHPV types (P<0.05; OR, 2.345) were significantly related to residual/recurrent CIN following surgical treatment. CONCLUSION: HPV load before treatment and infection with multiple hrHPV types were predictors of postoperative hrHPV persistence. HPV 53 was the type most likely to persist, but HPV 16 was the type that was most closely associated with residual/recurrent CIN-2/3.

Supplemental Trichomonas vaginalis testing is required to maintain control following a transition from Pap smear to HPV DNA testing for cervical screening: a mathematical modelling study.

OBJECTIVES: Using mathematical modelling, we have previously shown that the prevalence of infection with Trichomonas vaginalis (TV) is likely to increase in the general population in Australia with the transition from Pap smear-based cervical screening to human papillomavirus (HPV) DNA testing. Here we use the existing model to estimate the level of supplemental testing required to maintain TV control. METHODS: A compartmental mathematical model describing the transmission of TV in the general heterosexual population in Australia was used to evaluate the impact of a range of screening scenarios on TV prevalence over time following the transition to HPV DNA testing for cervical screening. Scenarios considered were the inclusion of a TV test with the HPV test and the addition of TV testing to routine chlamydia testing conducted in primary care. RESULTS: Our modelling suggests that with sufficient coverage, inclusion of TV testing with routine chlamydia screening in general practice, TV prevalence can be reduced over time, but at the current reported coverage will gradually increase following the transition to HPV testing. Inclusion of TV testing with HPV testing in the cervical screening programme is preferable to no supplemental testing but is considerably less effective in controlling TV. CONCLUSIONS: These findings support the inclusion of TV testing with routine chlamydia testing of young people.

The cost-effectiveness of human papillomavirus self-collection among cervical cancer screening non-attenders in El Salvador.

Cervical cancer screening with human papillomavirus (HPV) DNA testing has been incorporated into El Salvador's national guidelines. The feasibility of home-based HPV self-collection among women who do not attend screening at the clinic (i.e., non-attenders) has been demonstrated, but cost-effectiveness has not been evaluated. Using cost and compliance data from El Salvador, we informed a mathematical microsimulation model of HPV infection and cervical carcinogenesis to conduct a cost-effectiveness analysis from the societal perspective. We estimated the reduction in cervical cancer risk, lifetime cost per woman (2017 US$), life expectancy, and incremental cost-effectiveness ratio (ICER, 2017 US$ per year of life saved [YLS]) of a program with home-based self-collection of HPV (facilitated by health promoters) for the 18% of women reluctant to screen at the clinic. The model was calibrated to epidemiologic data from El Salvador. We evaluated health and economic outcomes of the self-collection intervention for women aged 30 to 59 years, alone and in concert with clinic-based HPV provider-collection. Home-based self-collection of HPV was projected to reduce population cervical cancer risk by 14% and cost $1210 per YLS compared to no screening. An integrated program reaching 99% coverage with both provider- and home-based self-collection of HPV reduced cancer risk by 74% (compared to no screening), and cost $1210 per YLS compared to provider-collection alone. Self-collection facilitated by health promoters is a cost-effective strategy for increasing screening uptake in El Salvador.

The cost-effectiveness of implementing HPV testing for cervical cancer screening in El Salvador.

OBJECTIVE: To assess the cost-effectiveness of HPV-based screening and management algorithms for HPV-positive women in phase 2 of the Cervical Cancer Prevention in El Salvador (CAPE) demonstration, relative to the status quo of Pap-based screening. METHODS: Data from phase 2 of the CAPE demonstration (n=8000 women) were used to inform a mathematical model of HPV infection and cervical cancer. The model was used to project the lifetime health and economic outcomes of HPV testing every 5 years (age 30-65 years), with referral to colposcopy for HPV-positive women; HPV testing every 5 years (age 30-65 years), with immediate cryotherapy for eligible HPV-positive women; and Pap testing every 2 years (age 20-65 years), with referral to colposcopy for Pap-positive women. RESULTS: Despite slight decreases in the proportion of HPV-positive women who received treatment relative to phase 1, the health impact of screening in phase 2 remained stable, reducing cancer risk by 58.5%. As in phase 1, HPV testing followed by cryotherapy for eligible HPV-positive women remained the least costly and most effective strategy (US$490 per year of life saved). CONCLUSION: HPV-based screening followed by immediate cryotherapy in all eligible women would be very cost-effective in El Salvador.

[Staging of oropharyngeal carcinomas : New TNM classification as a challenge for head and neck cancer centers]. / Staging von Oropharynxkarzinomen : Neue TNM-Klassifikation als Herausforderung für Kopf-Hals-Tumorzentren.

BACKGROUND: The TNM (tumor, nodes, metastasis) classification is updated periodically according to the literature and international recommendations. With the 8th edition, notable changes have been developed especially with regard to oropharyngeal cancer. MATERIALS AND METHODS: The modifications as well as the practicability of the classification for staging of oropharyngeal cancers are demonstrated on the basis of cases from the tumor database. RESULTS: The latest edition of the TNM classification realizes requirements to differentiate between human papilloma virus (HPV) positive and HPV-negative tumors during staging. Furthermore, the prognostic relevance of extranodal extension of lymph node metastases was integrated into the classification. While downstaging is performed regarding N category and Union Internationale Contre le Cancer (UICC) stage in many p16-positive tumors, for p16-negative tumors, extranodal spread mostly leads to a notable upstaging. Due to limited specificity of the p16 immunostaining, the relevance of false positive results has to be underlined. Missing integration of smoking behavior, limited standardization of the extranodal extension examination technique, as well as high demands on the documentation quality should be kept in mind. CONCLUSION: Clinical trials will have to show whether deescalation strategies regarding p16-positive carcinomas are supported by the changes made in the TNM staging system. A prospective multicenter study should examine the universal applicability, the appropriateness for all sublocations, as well as the prognostic significance of the current edition.

Estimating the value of point-of-care HPV testing in three low- and middle-income countries: a modeling study.

BACKGROUND: Where resources are available, the World Health Organization recommends cervical cancer screening with human papillomavirus (HPV) DNA testing and subsequent treatment of HPV-positive women with timely cryotherapy. Newer technologies may facilitate a same-day screen-and-treat approach, but these testing systems are generally too expensive for widespread use in low-resource settings. METHODS: To assess the value of a hypothetical point-of-care HPV test, we used a mathematical simulation model of the natural history of HPV and data from the START-UP multi-site demonstration project to estimate the health benefits and costs associated with a shift from a 2-visit approach (requiring a return visit for treatment) to 1-visit HPV testing (i.e., screen-and-treat). We estimated the incremental net monetary benefit (INMB), which represents the maximum additional lifetime cost per woman that could be incurred for a new point-of-care HPV test to be cost-effective, depending on expected loss to follow-up between visits (LTFU) in a given setting. RESULTS: For screening three times in a lifetime at 100% coverage of the target population, when LTFU was 10%, the INMB of the 1-visit relative to the 2-visit approach was I$13 in India, I$36 in Nicaragua, and I$17 in Uganda. If LTFU was 30% or greater, the INMB values for the 1-visit approach in all countries was equivalent to or exceeded total lifetime costs associated with screening three times in a lifetime. At a LTFU level of 70%, the INMB of the 1-visit approach was I$127 in India, I$399 in Nicaragua, and I$121 in Uganda. CONCLUSIONS: These findings indicate that point-of-care technology for cervical cancer screening may be worthy of high investment if linkage to treatment can be assured, particularly in settings where LTFU is high.

Evaluation of the Xpert® HPV assay in the detection of Human Papillomavirus in formalin-fixed paraffin-embedded oropharyngeal carcinomas.

OBJECTIVES: The increasing incidence of HPV-related Oropharyngeal Squamous Cell Carcinoma (OPSCC) and the improved survival of HPV-positive OPSCC highlight the need for effective tools in evaluating HPV status on formalin-fixed paraffin-embedded (FFPE) cancers. To date, there is no agreement regarding the most appropriate method for HPV testing on FFPE materials. We aimed to investigate the performance of the Xpert® HPV assay (Cepheid) on crude lysates from OPSCC FFPE tissues. MATERIALS AND METHODS: Crude lysates were obtained by proteinase K digestion of FFPE tissues that had already been analyzed by the INNO-LiPA HPV assay and p16ink4a immunostaining. RESULTS: 159 FFPE OPSCCs were evaluated. All the samples provided valid results with the Xpert, whereas three samples (1.8%) were invalid using the INNO-LiPA. Among the remaining 156 cases, 65 (41.7%) were concordantly positive and 87 (55.8%) concordantly negative (raw agreement 0.97, 95% CI: 0.93-0.99; Cohen K 0.95, 95% CI: 0.90-0.99). Type-specific data for the cases that were positive by both methods were completely concordant. Three samples were HPV16-positive with Xpert but negative with INNO-LiPA, while one OPSCC tested negative with Xpert and positive with INNO-LiPA. A very good agreement was observed between the Xpert and the p16 results, which was slightly higher than that for INNO-LiPA (Cohen K 0.87vs. 0.85). CONCLUSION: The Xpert HPV assay appears to be a very good method for HPV detection and genotyping on FFPE OPSCCs, and requires no prior purification of nucleic acids. This assay showed a very good agreement with INNO-LiPA and p16 findings.

Detection of High-Risk Human Papillomavirus in Cervix Sample in an 11. 3-year Follow-Up after Vaccination against HPV 16/18 / Detecção de papilomavírus humano de alto risco em amostras de colo uterino em 11. 3 anos de acompanhamento após vacinação contra HPV 16/18

Abstract Purpose the aim of this study was to evaluate the pattern of human papillomavirus (HPV) detection in an 11.3-year post-vaccination period in a cohort of adolescent and young women vaccinated or not against HPV 16/18. Methods a subset of 91 women from a single center participating in a randomized clinical trial (2001-2010, NCT00689741/00120848/00518336) with HPV 16/18 AS04- adjuvanted vaccine was evaluated. All women received three doses of the HPV vaccine (n = 48) or a placebo (n = 43), and cervical samples were collected at 6-month intervals. Only in this center, one additional evaluation was performed in 2012. Up to 1,492 cervical samples were tested for HPV-DNA and genotyped with polymerase chain reaction (PCR). The vaccine group characteristics were compared by Chi-square or Fisher exact or Mann-Whitney test. The high-risk (HR)-HPV 6-month-persistent infection rate was calculated. The cumulative infection by HPV group was evaluated by the Kaplan-Meier method and the log-rank test. Results the cumulative infection with any type of HPV in an 11.3-year period was 67% in the HPV vaccine group and 72% in the placebo group (p = 0.408). The longitudinal analysis showed an increase of 4% per year at risk for detection of HR-HPV (non-HPV 16/ 18) over time (p = 0.015), unrelated to vaccination. The cumulative infection with HPV 16/18 was 4% for the HPV vaccine group and 29% for the placebo group (p = 0.003). There were 43 episodes of HR-HPV 6-month persistent infection, unrelated to vaccination. Conclusions this study showed themaintenance of viral detection rate accumulating HR-HPV (non-HPV-16-18) positive tests during a long period post-vaccination, regardless of prior vaccination. This signalizes that the high number of HPV-positive testsmay be maintained after vaccination.

Resumo Objetivos avaliar o padrão de detecção do papilomavírus humano (HPV) em um período de 11.3 anos após a vacinação em uma coorte de adolescentes e mulheres jovens vacinadas ou não contra HPV 16/18. Métodos avaliou-se um subgrupo de 91 mulheres de um único centro, participantes de ensaio clínico randomizado (2001-2010, NCT00689741/00120848/00518336) com a vacina contra HPV 16/18 com adjuvante AS04. Todas as mulheres receberam três doses de vacina contra HPV (n = 48) ou placebo (n = 43), e tiveram amostras cervicais coletadas em intervalos de 6 meses. Somente neste centro, uma avaliação adicional foi realizada em 2012. Um total de 1.492 amostras cervicais foram testadas para DNA-HPV e genotipadas com reação em cadeia da polimerase (RCP). As características dos grupos de vacina contra HPV ou placebo foram comparadas pelo teste de Qui-quadrado ou teste exato de Fisher ou teste de Mann-Whitney. A infecção persistente por 6meses pelo HPV de alto risco (AR) foi calculada. A infecção cumulativa por grupo foi avaliada pelo método de Kaplan-Meier e pelo teste log-rank. Resultados a infecção cumulativa com qualquer tipo de HPV em11.3 anos foi de 67% no grupo vacina contra HPV e de 72% no grupo placebo (p = 0,408). A análise longitudinal mostrou um aumento de 4% ao ano no risco de detecção de HR-HPV (não-HPV 16/18) ao longo do tempo (p = 0,015), não relacionado com a vacinação. A infecção cumulativa com HPV 16/18 foi de 4% para o grupo vacina contra HPV e 29% para o grupo placebo (p = 0,003). Houve 43 episódios de infecção persistente por 6 meses por HR-HPV, não relacionados com a vacinação. Conclusões este estudo mostrou a manutenção da taxa de detecção viral, acumulando testes positivos de HR-HPV (não HPV-16-18) durante longo período pósvacinação, independentemente da vacinação prévia. Isto sinaliza que a alta positividade dos testes de HPV pode ser mantida após a vacinação.

The health and economic impact of scaling cervical cancer prevention in 50 low- and lower-middle-income countries.

OBJECTIVE: To estimate the health impact, financial costs, and cost-effectiveness of scaling-up coverage of human papillomavirus (HPV) vaccination (young girls) and cervical cancer screening (women of screening age) for women in countries that will likely need donor assistance. METHODS: We used a model-based approach to synthesize population, demographic, and epidemiological data from 50 low- and lower-middle-income countries. Models were used to project the costs (US $), lifetime health impact (cervical cancer cases, deaths averted), and cost-effectiveness (US $ per disability adjusted life year [DALY] averted) of: (1) two-dose HPV-16/18 vaccination of girls aged 10 years; (2) once-in-a-lifetime screening, with treatment when needed, of women aged 35 years with either HPV DNA testing or visual inspection with acetic acid (VIA); and (3) cervical cancer treatment over a 10-year roll-out. RESULTS: We estimated that both HPV vaccination and screening would be very cost-effective, and a comprehensive program could avert 5.2 million cases, 3.7 million deaths, and 22.0 million DALYs over the lifetimes of the intervention cohorts for a total 10-year program cost of US $3.2 billion. CONCLUSION: Investment in HPV vaccination of young girls and cervical cancer screen-and-treat programs in low- and lower-middle-income countries could avert a substantial burden of disease while providing good value for public health dollars.

Understanding women's hesitancy to undergo less frequent cervical cancer screening.

Inappropriate cervical cancer screening (e.g., screening too often) can result in unnecessary medical procedures, treatment, and psychological distress. To balance the benefits and harms, cervical cancer screening guidelines were recently modified in favor of less frequent screening (i.e., every 3 to 5 years). This study investigated women's acceptance of less frequent cervical cancer screening and their primary concerns about extending the screening interval beyond one year. A national sample of 376 U.S. women ages 21-65 completed an online survey in 2014. Predictors of willingness to get a Pap test every 3 to 5 years were identified using logistic regression. We also examined perceived consequences of less frequent screening. Over two thirds were willing to undergo less frequent screening if it was recommended by their healthcare provider. Nevertheless, nearly 20% expressed discomfort with less frequent screening and 45% were either in opposition or unsure whether they would be comfortable replacing Pap testing with primary HPV testing. Women whose most recent Pap test was (vs. was not) within the past year and women who ever (vs. never) had an abnormal Pap test were less willing to extend the screening interval. Additionally, women who typically saw an obstetrician/gynecologist or nurse practitioner for their Pap test (vs. a family physician) were less accepting of the guidelines. Hesitancy about the longer screening interval appears to stem from concern about developing cancer between screenings. Findings contribute to the growing body of research on cancer overscreening and may inform interventions for improving adherence to cancer screening guidelines.

[Relevance of HPV infections in head and neck cancers : Highlights of the 2016 ASCO Annual Meeting]. / Relevanz der HPV-Infektionen bei Kopf-Hals-Karzinomen : Highlights der ASCO-Jahrestagung 2016.

The papers on human papillomavirus (HPV) infections in head and neck carcinomas presented during the ASCO Meeting in 2016 investigated factors influencing the survival of patients with known HPV status. Interestingly, women suffering from oropharyngeal carcinomas show better survival than men do. This is believed to be the consequence of differences in the immune system of male and female patients. Another interesting finding is that the HPV status in cases of locoregional recurrence of oropharyngeal carcinomas represents a positive predictive marker for patient survival. Other papers presented at the meeting compared methods used to reliably determine HPV-driven carcinomas. Of particular interest is the development of a new in situ hybridization method to determine the viral mRNA of the oncogenes E6 and E7. The results presented appear promising with regard to their accuracy in detecting HPV-driven carcinomas. Another set of papers investigated, partly in retrospective settings, interventional studies in which the HPV status of the patients was taken into account. It is noteworthy that the high doses of cisplatin that were tested in comparison with weekly administered cisplatin or the treatment with cetuximab instead of cisplatin showed positive effects in some survival calculations but were accompanied by higher toxicity. Overall the papers presented demonstrate the necessity for further epidemiologic, methodological, interventional, and in particular prospective studies.

Cervical cancer screening: from Pap smear to future strategies / Triagem de câncer do colo uterino: do teste de Papanicolaou a estratégias futuras

ABSTRACT Previously, the screening for detection of cervical cancer was performed by simple cervicovaginal sample collected by the physician whenever the patient attended the medical consultation, and soon it was established as the annual"Pap smear". Since then, an elementary test has evolved into a complex process with multiple algorithms for the identification of invasive disease. The detection of human papillomavirus (HPV) has become part of the new screening recommendations, resulting in major changes in the guidelines. This review intends to emphasize the most important topics that are part of cervical cancer screening, including cervical cytology and HPV detection, and to discuss particular aspects of cervical cancer in Brazil. Despite the great benefits achieved by the cervical cancer screening programs with cytology and HPV test, there are still important issues to be discussed and improved in defining future strategies, including simplicity and possible application in different socioeconomic contexts, definition of the best test or tests to be applied and recommended interval, minimizing possible harms. After the establishment of screening algorithms well defined by leading organizations, management protocols should be disseminated among physicians and patients by education programs.

RESUMO Inicialmente, a triagem para detecção do câncer de colo uterino era feita por meio de uma simples amostra cervicovaginal colhida pelo médico, sempre que o paciente comparecia à consulta médica; logo se estabeleceu como"exame de Papanicolaou" anual. Desde então, um teste elementar evoluiu para um processo complexo, com múltiplos algoritmos para identificação de doença invasiva. A detecção do papilomavírus humano (HPV) tornou-se parte das novas recomendações de triagem, resultando em grandes mudanças nas diretrizes. Esta revisão pretende enfatizar os tópicos mais importantes que fazem parte do rastreamento do câncer de colo do útero, incluindo citologia cervical e detecção do HPV, bem como discutir aspectos particulares do câncer de colo do útero no Brasil. Apesar dos grandes benefícios alcançados pelos programas de rastreamento do câncer de colo uterino por meio do uso da citologia e do teste de HPV, existem ainda pontos importantes a serem discutidos e melhorados na definição de estratégias futuras, como simplicidade e possível aplicação em diferentes contextos socioeconômicos, definição do melhor teste ou testes a serem aplicados e intervalo recomendável, minimizando possíveis danos. Após o estabelecimento de algoritmos de rastreamento bem definidos pelas principais organizações, protocolos de manejo devem ser divulgados entre médicos e pacientes por programas de educação.

Can the careHPV test performed in mobile units replace cytology for screening in rural and remote areas?

BACKGROUND: Human papillomavirus (HPV) DNA testing can be crucial for women who have limited access to traditional screening. The current study compared the results obtained through HPV DNA testing with those obtained through cytology-based screening. METHODS: A total of 3068 women aged 18 to 85 years were enrolled in an opportunistic cervical cancer screening program developed by the Barretos Cancer Hospital and performed by a team of health professionals working within a mobile unit from March to December 2012, followed by statistical analyses. For each patient, 2 different cervical samples were collected and preserved in a careHPV assay and SurePath medium, respectively. RESULTS: High-risk HPV (hr-HPV) DNA was detected in 10.0% of women, with the majority (86.7%) demonstrating no abnormal Papanicolaou test results. The following cytological samples were found to be hr-HPV positive: 8.2% of the normal samples; 39.4% of the samples with atypical squamous/glandular cells of undetermined significance; 38.5% of the samples with atypical squamous/glandular cells of undetermined significance, cannot exclude high-grade lesion; 55.3% of the samples with low-grade squamous intraepithelial lesions; and 100% of the samples with high-grade squamous intraepithelial lesions. Colposcopy examinations were performed among 33.4% of the women with positive results on at least 1 of the tests (HPV DNA positive and/or cytology with atypical squamous/glandular cells of undetermined significance, cannot exclude high-grade lesion or high-grade squamous intraepithelial lesions), and 59.5% of these women underwent biopsies. Among these samples, 18.2% were confirmed as cervical intraepithelial neoplasia. CONCLUSIONS: The careHPV test was demonstrated to be a feasible alternative to primary screening in low-resource settings accessed through the use of mobile units. Cancer Cytopathol 2016;124:581-8. © 2016 American Cancer Society.

HPV detection in floor of mouth squamous cell carcinoma by PCR amplification / Detecção do HPV em carcinoma espinocelular de assoalho de boca por amplificação da PCR

ABSTRACT Introduction: Studies conducted during the last years, using new technologies for viral detection, permit to consider human papillomavirus (HPV) an etiologic factor for cervical cancer. Besides the relation to genital regions, other anatomic sites have been associated with HPV, including head and neck regions. Objectives: To investigate the prevalence of HPV infection in 35 samples from paraffin-embedded tissues using polymerase chain reaction (PCR)-deoxyribonucleic acid (DNA) amplification, and correlate it with demographic, clinical, and morphological factors and prognosis. Materials and methods: All samples were first amplified with human β-globin gene primers. Samples with positive amplification were subjected to HPV-DNA detection with general GP5 and GP6 primers. Results Only 30 samples were amplified for the β-globin gene. No floor of mouth squamous cell carcinoma cases showed amplification of HPV DNA. Discussion: The absence of HPV-DNA amplification does not suggest that this virus is absent from the process of oral carcinogenesis, since the selected sample is not in the risk group for the development of oral cancer associated with HPV infection. Conclusions: No correlation was found between HPV infection and floor of mouth carcinogenesis, however further studies are necessary.

RESUMO Introdução: Estudos realizados durante os últimos anos permitem considerar a infecção pelopapilomavírus humano (HPV) um fator etiológico para o câncer cervical. Apesar da íntima relação desse vírus com as regiões genitais, outras localizações anatômicas têm sido associadas a tal infecção, inclusive as regiões de cabeça e pescoço. Objetivos: Investigar a prevalência da infecção pelo HPV em 35 amostras parafinadas de carcinoma espinocelular de assoalho de boca, utilizando a amplificação da reação em cadeia dapolimerase (PCR) como método de detecção do ácido desoxirribonucleico (DNA) viral, bem como correlacionar aspectos demográficos, clínicos e morfológicos com o prognóstico da doença. Materiais e métodos: Todas as amostras foram inicialmente amplificadas com o primerpara detecção do gene da β-globina humana. As que tiveram amplificação positiva para o gene da β-globina foram então submetidas à detecção do DNA viral com os primers GP5 e GP6. Resultados: Apenas 30 amostras foram amplificadas para o gene β-globin. Nenhuma das amostras de carcinoma de assoalho de boca demonstrou resultado positivo para amplificação do DNA viral. Discussão: Apesar de a influência do vírus na carcinogênese oral não ter sido comprovada devido à ausência de DNA viral nas amostras, a relação não pode ser descartada, uma vez que as amostras selecionadas não se encontravam em grupo de risco para o desenvolvimento de carcinoma espinocelular de boca associado à infecção pelo HPV. Conclusão: Não foi detectada relação entre a infecção pelo HPV e o carcinoma de assoalho de boca, no entanto mais estudos são necessários sobre o tema.

High risk HPV testing following treatment for cervical intraepithelial neoplasia.

AIM: To determine the results of combined cytology and high-risk human papilloma virus (HR HPV) tests at 6 and 18 months postcolposcopy treatment at one Irish colposcopy centre. METHODS: All women who attended the centre's colposcopy smear clinic for a co-test 6 months (initial test) posttreatment were included in the audit (n = 251). RESULTS: The results revealed negative HR HPV for 79 % (n = 198) of women tested 6 months after treatment and positive results for 21 % (n = 53). HR HPV testing was more sensitive than cytology and led to early detection of residual disease. No women with negative HR HPV had high-grade cytology. CONCLUSION: HR HPV is more sensitive than cytology for detection of persistent CIN. However, 19 women with positive HR HPV had normal colposcopy with no persistent CIN detected. A national cost-benefit analysis is recommended to determine the value of the second co-test.

Cervical cancer screening in low-resource settings: A cost-effectiveness framework for valuing tradeoffs between test performance and program coverage.

As cervical cancer screening programs are implemented in low-resource settings, protocols are needed to maximize health benefits under operational constraints. Our objective was to develop a framework for examining health and economic tradeoffs between screening test sensitivity, population coverage and follow-up of screen-positive women, to help decision makers identify where program investments yield the greatest value. As an illustrative example, we used an individual-based Monte Carlo simulation model of the natural history of human papillomavirus (HPV) and cervical cancer calibrated to epidemiologic data from Uganda. We assumed once in a lifetime screening at age 35 with two-visit HPV DNA testing or one-visit visual inspection with acetic acid (VIA). We assessed the health and economic tradeoffs that arise between (i) test sensitivity and screening coverage; (ii) test sensitivity and loss to follow-up (LTFU) of screen-positive women; and (iii) test sensitivity, screening coverage and LTFU simultaneously. The decline in health benefits associated with sacrificing HPV DNA test sensitivity by 20% (e.g., shifting from provider- to self-collection of specimens) could be offset by gains in coverage if coverage increased by at least 20%. When LTFU was 10%, two-visit HPV DNA testing with 80-90% sensitivity was more effective and more cost-effective than one-visit VIA with 40% sensitivity and yielded greater health benefits than VIA even as VIA sensitivity increased to 60% and HPV test sensitivity declined to 70%. As LTFU increased, two-visit HPV DNA testing became more costly and less effective than one-visit VIA. Setting-specific data on achievable test sensitivity, coverage, follow-up rates and programmatic costs are needed to guide decision making for cervical cancer screening.

The comparative and cost-effectiveness of HPV-based cervical cancer screening algorithms in El Salvador.

Cervical cancer is the leading cause of cancer death among women in El Salvador. Utilizing data from the Cervical Cancer Prevention in El Salvador (CAPE) demonstration project, we assessed the health and economic impact of HPV-based screening and two different algorithms for the management of women who test HPV-positive, relative to existing Pap-based screening. We calibrated a mathematical model of cervical cancer to epidemiologic data from El Salvador and compared three screening algorithms for women aged 30-65 years: (i) HPV screening every 5 years followed by referral to colposcopy for HPV-positive women (Colposcopy Management [CM]); (ii) HPV screening every 5 years followed by treatment with cryotherapy for eligible HPV-positive women (Screen and Treat [ST]); and (iii) Pap screening every 2 years followed by referral to colposcopy for Pap-positive women (Pap). Potential harms and complications associated with overtreatment were not assessed. Under base case assumptions of 65% screening coverage, HPV-based screening was more effective than Pap, reducing cancer risk by ∼ 60% (Pap: 50%). ST was the least costly strategy, and cost $2,040 per year of life saved. ST remained the most attractive strategy as visit compliance, costs, coverage, and test performance were varied. We conclude that a screen-and-treat algorithm within an HPV-based screening program is very cost-effective in El Salvador, with a cost-effectiveness ratio below per capita GDP.