Células escamosas atípicas cervicais: conduta clínica / Cervical atypical squamous cells: clinical management

O diagnóstico precoce e o rastreamento das lesões precursoras do câncer do colo uterino são de extrema importância. O diagnóstico citológico ainda é a principal ferramenta para a prevenção. O uso de testes para detectar o DNA-HPV associado à citologia tem sido proposto, visto que existem evidências epidemiológicas de que o papilomavírus humanos (HPV) é causa necessária para a ocorrência do câncer cervical. De acordo com a classificação de Bethesda 2001, células escamosas atípicas (ASC) são alterações citológicas sugestivas de lesão intraepitelial, qualitativa ou quantitativamente insuficientes para uma interpretação definitiva. Elas são subdivididas em ASC-US (células escamosas atípicas de significado indeterminado possivelmente não neoplásicas) e ASC-H (células escamosas atípicas não sendo possível excluir lesão intraepitelial de alto grau). O seguimento ideal para mulheres com diagnóstico de ASC é controverso e existem dúvidas sobre como realizá-lo, bem como qual o tratamento mais apropriado. O objetivo desta revisão consiste em avaliar o seguimento e tratamento das mulheres com diagnóstico citológico de ASC. Foi realizada revisão da literatura de estudos indexados em banco de dados como MEDLINE, PubMed e LILACS.

Early diagnosis and screening of precursor lesions of cervical cancer are extremely important. The cytological diagnosis is still the main tool to prevention. The use of tests to detect DNA-HPV combined with cytology has been proposed, since there are epidemiological evidences that human papillomavirus (HPV) is a necessary cause for the occurrence of cervical cancer. According to the 2001 Bethesda classification atypical squamous cells (ASC), there are cytological changes suggestive of squamous intraepithelial lesion that are qualitatively or quantitatively insufficient for a definitive interpretation. It is subdivided into ASC-US (atypical squamous cells of undetermined significance may not neoplastic) and ASC-H (atypical squamous cells is not possible to exclude high-grade intraepithelial lesion). The ideal follow-up for women diagnosed with ASC is controversial and there are doubts about how to accomplish it and the most appropriate treatment. The objective of this review is to evaluate the monitoring and treatment of women with cytological diagnosis of ASC. We performed a literature review of studies indexed in databases such as MEDLINE, PubMed and LILACS.

Promising strategies for cervical cancer screening in the post-human papillomavirus vaccination era.

Human papillomavirus (HPV) vaccination is expected to reduce the burden of cervical cancer in most settings; however, it is also expected to interfere with the effectiveness of screening. In the future, maintaining Pap cytology as the primary cervical screening test may become too costly. As the prevalence of cervical dysplasias decreases, the positive predictive value of the Pap test will also decrease, and, as a result, more women will be referred for unnecessary diagnostic procedures and follow-up. HPV DNA testing has recently emerged as the most likely candidate to replace cytology for primary screening. It is less prone to human error and much more sensitive than the Pap smear in detecting high-grade cervical lesions. Incorporating this test would improve the overall quality of screening programs and allow spacing out screening tests, while maintaining safety and lowering costs. Although HPV testing is less specific than Pap cytology, this issue could be resolved by reserving the latter for the more labour-efficient task of triaging HPV-positive cases. Because most HPV-positive smears would contain relevant abnormalities, Pap cytology would be expected to perform with sufficient accuracy under these circumstances. HPV Pap triage would also provide a low-cost strategy to monitor long-term vaccine efficacy. Although demonstration projects could start implementing HPV testing as a population screening tool, more research is needed to determine the optimal age to initiate screening, the role of HPV typing and other markers of disease progression, and appropriate follow-up algorithms for HPV-positive and Pap-negative women.

Cost-effectiveness of conventional cytology and HPV DNA testing for cervical cancer screening in Colombia.

OBJECTIVE: To assess cost-effectiveness of conventional cytology and HPV DNA testing for cervical-cancer screening in Colombia. MATERIAL AND METHODS: The National Cancer Institute of Colombia (NCIC) in 2007 developed a Markov model on the natural history of cervical cancer; no screening, conventional cytology, and HPV DNA testing were compared. Only direct costs were used. Outcomes comprise cervical cancer mortality, years of life saved, and lifetime costs. Discounted incremental cost-effectiveness ratios were estimated and sensitivity analyses were conducted for key parameters. RESULTS: Depending on the screening strategy a 69-81% mortality reduction might be expected. The HPV DNA testing every five years is a cost-effective strategy (Incremental Cost-Effectiveness Ratio (ICER): USD$44/YLS) if the cost per test is under USD$31. The effectiveness was sensitive to coverage and primarily to follow-up. CONCLUSIONS: HPV DNA testing is a cost-effective alternative for screening in Colombia. Not only high coverage but high follow-up rates are critical for successful screening programs.

Cost-effectiveness of conventional cytology and HPV DNA testing for cervical cancer screening in Colombia / Costo-efectividad de la citología y la tamización con pruebas de ADN-VPH para cáncer de cuello uterino en Colombia

OBJECTIVE: To assess cost-effectiveness of conventional cytology and HPV DNA testing for cervical-cancer screening in Colombia. MATERIAL AND METHODS: The National Cancer Institute of Colombia (NCIC) in 2007 developed a Markov model on the natural history of cervical cancer; no screening, conventional cytology, and HPV DNA testing were compared. Only direct costs were used. Outcomes comprise cervical cancer mortality, years of life saved, and lifetime costs. Discounted incremental cost-effectiveness ratios were estimated and sensitivity analyses were conducted for key parameters. RESULTS: Depending on the screening strategy a 69-81 percent mortality reduction might be expected. The HPV DNA testing every five years is a cost-effective strategy (Incremental Cost-Effectiveness Ratio (ICER): USD$44/YLS) if the cost per test is under USD$31. The effectiveness was sensitive to coverage and primarily to follow-up. CONCLUSIONS: HPV DNA testing is a cost-effective alternative for screening in Colombia. Not only high coverage but high follow-up rates are critical for successful screening programs.

OBJETIVO: evaluar el costo-efectividad de la citología convencional y la prueba de ADN-VPH para tamización de cáncer cervical en Colombia. MATERIAL Y MÉTODOS: el Instituto Nacional de Cancerología de Colombia construyó en 2007 un modelo de Markov de historia natural del cáncer cervical. Se comparó "no tamización", citología convencional y prueba de ADN-VPH. Se utilizaron costos directos. Los desenlaces fueron mortalidad, años de vida ganados y costos. Se calcularon razones de costo-efectividad incremental. Se realizaron análisis de sensibilidad para parámetros clave. RESULTADOS: la mortalidad se redujo 69-81 por ciento según la estrategia. La tamización con ADN-VPH cada cinco años es costo-efectiva (ICER (Razón de Costo-Efectividad incremental por sus siglas en inglés): 44 dólares por año de vida saludable) si los costos por prueba son menores a 31 dólares. La efectividad fue más sensible al seguimiento que a la cobertura. CONCLUSIONES: La tamización con prueba ADN-VPH es costo-efectiva para Colombia. No solamente altas coberturas, sino también altos porcentajes de seguimiento son críticos para el éxito de la tamización.

Cost-effectiveness analysis based on the atypical squamous cells of undetermined significance/low-grade squamous intraepithelial lesion Triage Study (ALTS).

BACKGROUND: The ALTS (atypical squamous cells of undetermined significance [ASCUS] and low-grade squamous intraepithelial lesion [LSIL] Triage Study) suggests that, for women diagnosed with ASCUS, human papillomavirus (HPV) DNA testing followed by referral to colposcopy of only those women with oncogenic HPV (i.e., HPV DNA testing) is as effective at detecting cervical intraepithelial neoplasia (CIN) 3 or cancer (CIN3+) as referring all women with ASCUS for immediate colposcopy. We conducted a cost-effectiveness analysis of the ALTS trial to determine whether HPV DNA testing is a cost-effective alternative to immediate colposcopy or conservative management with up to three cytology examinations. METHODS: Data from the ALTS trial were used in conjunction with medical care costs in a short-term decision model. The model compared the incremental costs per case of CIN3+ detected as measured by the incremental cost-effectiveness ratio (ICER) for the following management strategies for women with ASCUS: immediate colposcopy, HPV DNA testing, and conservative management with up to three cytology examinations. RESULTS: The least costly and least sensitive strategy was conservative management with one repeat cytology examination using a threshold of high-grade squamous intraepithelial lesion (HSIL) for referral to colposcopy. Compared with this strategy, triage to colposcopy based on a positive HPV DNA test result had an ICER of 3517 dollars per case of CIN3+ detected. Immediate colposcopy and conservative management with up to three repeat cytology visits detected fewer cases of CIN3+ and were more costly than HPV DNA testing. Immediate colposcopy became cost-effective at 20,370 dollars compared with HPV DNA testing only if colposcopy and biopsy were assumed to be 100% sensitive. CONCLUSIONS: HPV DNA testing is an economically viable strategy for triage of ASCUS cytology. The less than perfect sensitivity of colposcopy and biopsy needs to be accounted for in future clinical guidelines and policy analyses.

HPV DNA testing in the triage of atypical squamous cells of undetermined significance (ASCUS): cost comparison of two methods.

Human papillomavirus (HPV) DNA testing for triage of cervical cytologies showing atypical squamous cells of undetermined significance (ASCUS) has become the standard of practice. Currently, Hybrid Capture II (HCII) is the preferred method for ASCUS triage. In situ hybridization for HPV represents an alternative to HCII and appears to have a superior specificity but is more expensive. We compare the reimbursement rates of ASCUS triage (HPV high risk) using the methods of HCII and INFORM (in situ hybridization for HPV) in a series of 431 ASCUS patients. The patients were followed for 1 yr, during which each patient had either colposcopic biopsy or follow-up cervical cytology after ASCUS HPV DNA triage. Eighty-nine patients were excluded from the analysis because of incomplete follow-up. The HPV triage percentages, colposcopic biopsy positivity rates and cervical cytology positivity percentages were calculated for each method. The reimbursement rates of the tests/procedures used in the analysis were those in effect at the University of Utah in 2003. The total triage and follow-up reimbursement costs were calculated for HCII and INFORM and compared.HCII referred 19.9% of patients to colposcopy, with a biopsy positivity rate of 25.6% for dysplasia. INFORM referred 11.8% of patients to colposcopy, of whom 34% had a biopsy diagnosis of dysplasia. HCII negative cases revealed 19% to have ASCUS or higher on the follow-up cervical cytology, while 19.9% of INFORM negative cases had a reading of ASCUS or higher at follow-up cytologic examination. The 1-yr HPV DNA triage and follow-up reimbursements for HCII were 316,942.00 US dollars per 1,000 women, and for the INFORM methodology, the reimbursements were 369,484.00 US dollars per 1,000 women. The INFORM method was associated with higher specificity and sent fewer (41%) patients to colposcopy than did HCII. Although this smaller referral rate reduced reimbursement costs associated with colposcopy, the increased reimbursement paid for follow-up cytologies and office visits of HPV DNA negative patient and the greater cost of the INFORM test results in higher overall reimbursement for INFORM. Based on these costs and diagnostic accuracies, it appears that the INFORM HPV technology represents a viable option to HCII ASCUS triage. INFORM HPV appears to be 16% more expensive than HCII but has the advantage of sending 41% fewer women to colposcopy.