A steady 70% decline in mortality from cervical cancer has been observed since the mid-century after the introduction of widespread Papanicolaou (Pap) cytologic screening. This is a major success story for cancer control in the United States. In 2003, there were an estimated 12,200 new cases of invasive cervical cance4r and 4100 deaths. Although mortality from this cancer is no longer as common as in the past in the United States, cervical cancer is still the second most common cancer worldwide. In developed countries, fatalities from this disease should be entirely avoidable with currently available technology. Incidence and mortality are higher in women with no prior screening, those with concurrent human papillomavirus (HPV) infection, and women of lower socioeconomic status.
Newer methods of screening make use of increased understanding of the essential etiologic role of approximately 15 oncogenic types of HPV. Various combinations of HPV DNA testing; newer cytologic methods, especially liquid-based cytology; and traditional Pap smears offer opportunities to improve sensitivity and specificity of cervical cancer screening. However, traditional cytologic screening with Pap smears remains the primary method of screening.
The value of Pap smear screening is of little doubt, even though there has never been an RCT to confirm its efficacy. In the absence of an RCT, e3vidence for the effectiveness of cytologic screening has come from observed trends in countries with large national screening programs and case-control studies in varied geographic areas. When to start, when to stop, and the interval between tests have been important questions within the context of traditional cytologic screening.
Current U.S. recommendations are that screening should start approximately 3 years after the onset of sexual activity, at prevalence of HPV infection in young, sexually active women and the frequency of low and high grade sqamous intraepithelial lesions. However, up to 70 of high risk HPV infections are transient in young women in their 20s, and 90% of low grade squamous intraepithelial le4sions regress in this age group. Further more, incidence is not measurable until 20 to 24 years of age, when it is still only 1.7 per 100,000 per year. Given the low incidence of serious disease and the high likelihood of regression of early dyplastic lesions in younger women, there is concern that screening adolescents and women in their 20s could lead to over diagnosis, aggressive treatment, and unnecessary harm from ablative surgical procedures. To address this reality, some European countries (e.g., Denmark) do not start screening until age 30 years.
More than one-half of invasive cervical cancers occur in women who have never been screened, or at least it within the previous 5 years. Progress toward further reductions in death from this cancer could be made by concerted efforts to reach and screen such women. However, evidence is limited on the questions of the optimal interval between screening test. After its review of evidence, the U.S. Preventive Services Task Force left the interval variable from 1 to 3 years. The principal study on which this judgment was based was a comprehensive analysis of large-scale screening programs and case-control studies that used various designs and methods but which showed increased efficacy with shorter intervals up to annual testing. Sample size, even in this large analysis, was insufficient to distinguish efficacy with shorter intervals up to annual testing. Sample size, even in this large analysis, was insufficient to distinguish efficacy betwee3n intervals of every 2 versus every 3 years. A case-control study in a large, stable health plan population confirmed that annual screening is more likely to pickup invasive cervical cancers than is using an interval of every 2 years, and likewise for 2 versus 3 year intervals. The advantage was very small, and cost-effectiveness studies are needed. For women who have had hysterectomies for benign conditions, the likelihood of detecting vaginal dyplasia is extremely low and the false positive rate high. The continued practice of screening at any interval in this group is inappropriate.
Data are also inadequate on which to base recommendations for an upper age limit for regular screening. Although there is concern that Pap testing is less sensitive in order women because of a receded squamocolumnar junction of the cervix, the primary reason for invasive cervical cancer in older women is still lack of any screening.
International studies using DNA testing have demonstrated that almost all cervical cancers are associated with infection by sexually transmitted HPV. However HPV infection is highly transient in young women, and screening protocols that use HPV testing are still being evaluated. Protocols that add HPV DNA testing to the traditional Pap test for cytologic results of atypical squamous cells of undetermined significance (ASCUS) have demonstrated increased sensitivity over repeated Pap smear testing. Among 3488 women with ASCUS followed for 2 years in the ASCUS/LSIL (low-grade squamous intraepithelial lesion). Triage Study, HPV DNA testing was more sensitive for detecting cervical intraepithelial neoplasia 3 or invasive cancer and just as specific as repeat cytology. Comparisons of the multiple strategies now available, including visual screening, conventional cytology, liquid-based cytology, and HPV DNA testing, have found that either liquid-based cytology or HPV DNA testing provides a better balance between sensitivity and specificity for cervical intraepithelial neoplasia 3+ than conventional methods. However, although these new technologies are promising, the results are highly dependent on local resources and prevalence of disease. In most situations, clinicians are still likely to have their greatest effect by ensuring full coverage and follow-up for women who receive traditional cytologic screening. The challenge for the future may be less of a technical nature and more dependent on local finances and screening policies.
Newer methods of screening make use of increased understanding of the essential etiologic role of approximately 15 oncogenic types of HPV. Various combinations of HPV DNA testing; newer cytologic methods, especially liquid-based cytology; and traditional Pap smears offer opportunities to improve sensitivity and specificity of cervical cancer screening. However, traditional cytologic screening with Pap smears remains the primary method of screening.
The value of Pap smear screening is of little doubt, even though there has never been an RCT to confirm its efficacy. In the absence of an RCT, e3vidence for the effectiveness of cytologic screening has come from observed trends in countries with large national screening programs and case-control studies in varied geographic areas. When to start, when to stop, and the interval between tests have been important questions within the context of traditional cytologic screening.
Current U.S. recommendations are that screening should start approximately 3 years after the onset of sexual activity, at prevalence of HPV infection in young, sexually active women and the frequency of low and high grade sqamous intraepithelial lesions. However, up to 70 of high risk HPV infections are transient in young women in their 20s, and 90% of low grade squamous intraepithelial le4sions regress in this age group. Further more, incidence is not measurable until 20 to 24 years of age, when it is still only 1.7 per 100,000 per year. Given the low incidence of serious disease and the high likelihood of regression of early dyplastic lesions in younger women, there is concern that screening adolescents and women in their 20s could lead to over diagnosis, aggressive treatment, and unnecessary harm from ablative surgical procedures. To address this reality, some European countries (e.g., Denmark) do not start screening until age 30 years.
More than one-half of invasive cervical cancers occur in women who have never been screened, or at least it within the previous 5 years. Progress toward further reductions in death from this cancer could be made by concerted efforts to reach and screen such women. However, evidence is limited on the questions of the optimal interval between screening test. After its review of evidence, the U.S. Preventive Services Task Force left the interval variable from 1 to 3 years. The principal study on which this judgment was based was a comprehensive analysis of large-scale screening programs and case-control studies that used various designs and methods but which showed increased efficacy with shorter intervals up to annual testing. Sample size, even in this large analysis, was insufficient to distinguish efficacy with shorter intervals up to annual testing. Sample size, even in this large analysis, was insufficient to distinguish efficacy betwee3n intervals of every 2 versus every 3 years. A case-control study in a large, stable health plan population confirmed that annual screening is more likely to pickup invasive cervical cancers than is using an interval of every 2 years, and likewise for 2 versus 3 year intervals. The advantage was very small, and cost-effectiveness studies are needed. For women who have had hysterectomies for benign conditions, the likelihood of detecting vaginal dyplasia is extremely low and the false positive rate high. The continued practice of screening at any interval in this group is inappropriate.
Data are also inadequate on which to base recommendations for an upper age limit for regular screening. Although there is concern that Pap testing is less sensitive in order women because of a receded squamocolumnar junction of the cervix, the primary reason for invasive cervical cancer in older women is still lack of any screening.
International studies using DNA testing have demonstrated that almost all cervical cancers are associated with infection by sexually transmitted HPV. However HPV infection is highly transient in young women, and screening protocols that use HPV testing are still being evaluated. Protocols that add HPV DNA testing to the traditional Pap test for cytologic results of atypical squamous cells of undetermined significance (ASCUS) have demonstrated increased sensitivity over repeated Pap smear testing. Among 3488 women with ASCUS followed for 2 years in the ASCUS/LSIL (low-grade squamous intraepithelial lesion). Triage Study, HPV DNA testing was more sensitive for detecting cervical intraepithelial neoplasia 3 or invasive cancer and just as specific as repeat cytology. Comparisons of the multiple strategies now available, including visual screening, conventional cytology, liquid-based cytology, and HPV DNA testing, have found that either liquid-based cytology or HPV DNA testing provides a better balance between sensitivity and specificity for cervical intraepithelial neoplasia 3+ than conventional methods. However, although these new technologies are promising, the results are highly dependent on local resources and prevalence of disease. In most situations, clinicians are still likely to have their greatest effect by ensuring full coverage and follow-up for women who receive traditional cytologic screening. The challenge for the future may be less of a technical nature and more dependent on local finances and screening policies.
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