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Journal of virological methods 02/2013; · 2.13 Impact Factor
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Nicolas Wentzensen,
Chang Sun,
Arpita Ghosh, Walter Kinney,
Lisa Mirabello,
Sholom Wacholder,
Ruth Shaber,
Brandon Lamere,
Megan Clarke,
Attila T Lorincz,
Philip E Castle,
Mark Schiffman,
Robert D Burk
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ABSTRACT: Background
Persistent infections with carcinogenic human papillomavirus (HPV) types are the necessary cause of cervical cancer. We recently demonstrated that the HPV16 genome is strongly methylated in cervical precancer compared with transient infections. However, the extent of methylation in other HPV types and its role in progression to cancer is poorly understood.Methods
We analyzed whole-genome methylation patterns of the three next most carcinogenic HPV genotypes: HPV31 (closely related to HPV16), and two other closely related types, HPV18 and HPV45. DNA was extracted from cervical cytology specimens from 92 women with precancer and 96 women infected with HPV31, HPV18, or HPV45, but who had no cytological or histological abnormalities. After bisulfite modification, genome-wide pyrosequencing was performed covering 80-106 sites. We calculated differences in median methylation, odds ratios, areas under the curve, and Spearman rank correlation coefficients for methylation levels between different sites. All statistical tests were two-sided.ResultsFor all three HPV types, we observed strongly elevated methylation levels at multiple CpG sites in the E2, L2, and L1 regions among women with cervical intraepithelial neoplasia grade 3 compared with women with transient infections. We observed high correlation of methylation patterns between phylogenetically related types. The highest areas under the curve were 0.81 for HPV31, 0.85 for HPV18, and 0.98 for HPV45. Differential methylation patterns in cervical intraepithelial neoplasia grade 3 patients with multiple infections suggest that methylation can clarify which of the infections is causal.Conclusions
Carcinogenic HPV DNA methylation indicates transforming HPV infections. Our findings show that methylation of carcinogenic HPV types is a general phenomenon that warrants development of diagnostic assays.
CancerSpectrum Knowledge Environment 10/2012; · 14.07 Impact Factor
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Archives of internal medicine 05/2012; 172(13):1041-3. · 11.46 Impact Factor
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ABSTRACT: To characterize the antecedent screening of women 65 years of age and older diagnosed with cervical cancer.
Screening histories of women 65 years of age and older who were diagnosed with cervical cancer between 2003 and 2008 were examined utilizing the organization's databases and the regional Cancer Registry. Stopping screening was recommended at age 65 for members who had either 3 consecutive negative Paps or a single negative Pap plus HPV test ("cotest").
From 2003 through 2008 there were 56 Kaiser Permanente Northern California members 65 years of age and older diagnosed with cervical cancer. During the same time period there were 1,323,100 woman-years of membership in women age 65 and older. The risk of invasive cancer among women age 65 and older was 4.2/100,000/year in 2003-2008. 33 of 56 (59%) had one or more Pap smears prior to diagnosis. Of the 33, 14 women (25%) had 3 consecutive negative Pap smears prior to diagnosis. Three of 46,401 women with 1 or more negative cotests at age 65 and older were subsequently diagnosed with invasive cancer during 132,639 women-years of follow-up (2.3/100,000/year).
Most cervical cancers diagnosed at age 65 and older occur in women who have not met our criteria for stopping screening. A few cancers will continue to occur at age 65 and older despite multiple negative tests, as is true in other age groups. We currently have no evidence that these cancers would be prevented with continued screening at ages 65 and older.
Gynecologic Oncology 05/2012; 126(2):203-6. · 3.89 Impact Factor
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ABSTRACT: The cobas human papillomavirus (HPV) test (cobas) was recently approved by the U.S. Food and Drug Administration (FDA) and identifies HPV16 and HPV18 separately as well as detecting a pool of 11 HR-HPV genotypes (HPV31, -33, -35, -39, -45, -51, -52, -56, -58, -59, -68) and also HPV66. We compared cobas, Linear Array (LA), and Hybrid Capture 2 (HC2) assays for detection of carcinogenic HPV DNA, and cobas and LA for detection of HPV16 and HPV18 DNA, among the first 1,852 women enrolled in the HPV Persistence and Progression Cohort (PaP Cohort) study. Specimens were tested by all 3 assays 1 year after an HC2-positive result. In 1,824 specimens with cobas results, cobas had an 85.9% agreement with HC2 and 91.0% agreement with LA for carcinogenic HPV detection. When results between cobas and HC2 disagreed, cobas tended to call more women HPV positive (P < 0.01). Categorizing cobas and LA results hierarchically according to cancer risk (HPV16, HPV18, other carcinogenic HPV genotypes, or carcinogen negative), there was a 90% agreement for all categories of HPV (n = 1,824). We found good agreement between the two U.S. FDA-approved HPV tests, with discrepancies between the two assays due to specific characteristics of the individual assays. Additional studies are needed to compare HC2 and cobas for detecting and predicting CIN3 to understand the clinical implications of the discrepant test results between the two tests.
Journal of clinical microbiology 11/2011; 50(1):61-5. · 4.16 Impact Factor
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Philip E Castle,
Ruth Shaber,
Brandon J LaMere, Walter Kinney,
Barbara Fetterma,
Nancy Poitras,
Thomas Lorey,
Mark Schiffman,
Anne Dunne,
Janae M Ostolaza,
Sharod McKinney,
Robert D Burk
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ABSTRACT: The human papillomavirus (HPV) Persistence and Progression Cohort is a natural history study of carcinogenic HPV positive women. Here, we present the HPV genotypes found in first ∼500 cases of cervical intraepithelial neoplasia grade 3 (CIN3) or more severe disease (CIN3+) diagnosed at the study baseline.
Women aged 30 and older were screened for cervical cancer using Pap smears and tested for carcinogenic HPV using Hybrid Capture 2 (HC2; Qiagen). We randomly selected women who tested HPV positive and were diagnosed with CIN3+ (n = 448) or without CIN3+ (<CIN3; n = 830). Residual cervical Pap specimens were HPV genotyped using a MY09/11 L1-targeted PCR method.
Among HC2-positive women, HPV16 (48.9%), HPV31 (9.2%), and HPV18 (8.5%) were the most common HPV genotypes in CIN3+. There was a decrease at older ages in the fraction of CIN3 (P(trend) = 0.006), adenocarcinoma in situ (AIS) (P(trend) = 0.08), and CIN3/AIS (P(trend) = 0.002) associated with HPV16. Compared to the other carcinogenic HPV genotypes in aggregate, HPV18 was strongly associated with CIN3+ in women with a normal Pap [odds ratio (OR) = 5.7, 95% CI = 1.2-26] but not in women with abnormal Pap (OR = 1.3, 95% CI = 0.74-2.3).
HPV16 is more strongly associated with cervical precancer diagnosed in younger women (vs. older women). HPV18 infections were linked to precancerous lesions that were missed by cytology.
The progression timeline of HPV16 differs from other carcinogenic HPV genotypes, which may impact the use of HPV16 detection in the management of HPV-positive women.
Cancer Epidemiology Biomarkers & Prevention 03/2011; 20(5):946-53. · 4.12 Impact Factor
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ABSTRACT: To explore the effect of screening history on the risk of cervical precancer and cancer after an human papillomavirus (HPV)-positive test.
A large health maintenance organization introduced cytology and HPV cotesting into routine clinical practice in 2003. We selected women aged 30 and older who tested HPV positive, cytology negative between January 2006 and December 2008 who had any clinical follow-up documented before January 2010 (n=26,799). The 1-year and 4-year cumulative incidence rates and rate ratios for cervical intraepithelial neoplasia grade 2 or higher (CIN 2+) with 95% confidence intervals (95% CIs) were calculated as estimates of absolute risk and relative risk, respectively. Results were stratified on immediate past HPV test and Pap results.
Without consideration of past screening round, the 1-year and 4-year cumulative incidence rates for CIN 2+ after an HPV-positive, Pap-negative result were 2.83 (95% CI 2.55-3.12) and 7.89 (95% CI 7.00-8.78). However, risks varied substantially by past screening result. For example, the 4-year risk of CIN2+ was greater for women who had a past HPV-positive, Pap-negative result (cumulative incidence rate=11.79, 95% CI 10.22-13.36) compared with those who had HPV-negative, Pap-negative result (cumulative incidence rate=4.56, 95% CI 3.43-5.69; cumulative incidence rate ratio=2.59, 95% CI 2.30-2.87).
Because cervical precancer is associated with persistent HPV infection, the risk associated with an HPV-positive test can vary significantly depending on the immediate past screening round. Optimizing screening programs will require knowledge of screening history.
Obstetrics and Gynecology 03/2011; 117(3):650-6. · 4.73 Impact Factor
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ABSTRACT: Strong evidence now supports the adoption of cervical cancer prevention strategies that explicitly focus on persistent infection with the causal agent, human papillomavirus (HPV). To inform an evidence-based transition to a new public health approach for cervical cancer screening, we summarize the natural history and cervical carcinogenicity of HPV and discuss the promise and uncertainties of currently available screening methods. New HPV infections acquired at any age are virtually always benign, but persistent infections with one of approximately 12 carcinogenic HPV types explain virtually all cases of cervical cancer. In the absence of an overtly persistent HPV infection, the risk of cervical cancer is extremely low. Thus, HPV test results predict the risk of cervical cancer and its precursors (cervical intraepithelial neoplasia grade 3) better and longer than cytological or colposcopic abnormalities, which are signs of HPV infection. The logical and inevitable move to HPV-based cervical cancer prevention strategies will require longer screening intervals that will disrupt current gynecologic and cytology laboratory practices built on frequent screening. A major challenge will be implementing programs that do not overtreat HPV-positive women who do not have obvious long-term persistence of HPV or treatable lesions at the time of initial evaluation. The greatest potential for reduction in cervical cancer rates from HPV screening is in low-resource regions that can implement infrequent rounds of low-cost HPV testing and treatment.
CancerSpectrum Knowledge Environment 01/2011; 103(5):368-83. · 14.07 Impact Factor
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ABSTRACT: To characterize the 6- and 18-month cumulative risk of cervical intraepithelial neoplasia grade 2 or worse (CIN 2+) and grade 3 or worse (CIN 3+) in women aged 30 years and older after a low-grade squamous intraepithelial lesion (LSIL) cytology and high-risk human papillomavirus (HPV)-negative screening result in routine clinical practice.
Comprehensive quality assurance databases of screening test and biopsy results from the Regional Laboratory of the Kaiser Permanente Northern California Health Plan were reviewed. All women aged 30 years and older with LSIL cytology were sorted by high-risk HPV status. Associated biopsy results were tabulated, and the corresponding risks of CIN 2+ and CIN 3+ diagnosed within 18 months after LSIL cytology were calculated overall and by decade of age.
During the 6-year period, from 2003 to 2008, 4,113 LSIL cases were interpreted in women aged 30 years and older for which corresponding high-risk HPV and biopsy results were available. The proportion of women with LSIL testing positive for HPV declined with age, from 89% in the group aged 30 to 39 years to 76% in women older than 50 years (p < .001). Of 622 women with HPV-negative LSIL cytology, there was no case of cancer detected at colposcopy occurring within 6 months of the screening test. The 18-month risks of CIN 2+ and CIN 3+ were 3.5% and 1.4%, respectively.
The risk of CIN 3+ is sufficiently low in women aged 30 years and older with high-risk HPV-negative LSIL that 1 year follow-up rather than immediate colposcopy should be considered when it occurs in routine clinical practice.
Journal of Lower Genital Tract Disease 01/2011; 15(1):54-9. · 1.07 Impact Factor
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ABSTRACT: To characterize the cervical cancers diagnosed following a Pap-negative, high risk human papillomavirus (HPV)-positive (Pap-/HPV+) screen in routine clinical practice.
Using data from Kaiser Permanente Northern California, we investigated the cases of cervical cancer diagnosed between January, 2003 and January, 2009 following Pap-/HPV+ screen. Two cervical specimens were routinely collected for cervical cancer screening, one for conventional cytology and the other for high risk HPV testing using Hybrid Capture 2 (Qiagen).
Forty-four women (median age at diagnosis=44years) were diagnosed with primary invasive cervical cancer with a recent history of one or more Pap-/HPV+ screens. Twenty-six women had one Pap-/HPV+ screen preceding the diagnosis of cancer, 15 had two, and three had three. There were 16 squamous cancers, one small cell cancer, 24 adenocarcinomas, 2 adenosquamous carcinomas, and one case with separate invasive squamous and adenocarcinoma. FIGO Stage was IA in 11 women, IB in 31 women and IIA in 2 women. Treatment included a pelvic node dissection in 30, 2 (6.7%) of whom had positive nodes.
HPV testing contributes to early cervical cancer diagnosis detection in women with negative Pap tests. Most women in this cohort have early stage, node negative, treatable and potentially curable disease. Adenocarcinoma predominated as might be expected because cytology misses these cancers and their precursors. The majority of cancers were diagnosed following a single Pap-/HPV+ screen, suggesting that effective triage to colposcopy of women with a Pap-/HPV+ screen would be preferable to retesting in one year as currently recommended.
Gynecologic Oncology 01/2011; 121(2):309-13. · 3.89 Impact Factor
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ABSTRACT: Human papillomavirus (HPV) testing is more sensitive for the detection of cervical precancer and cancer than cervical cytology. The increased sensitivity of HPV testing and cytology combined ("cotesting") compared to cytology alone permitted professional societies to recommend 3-year screening intervals among the cotest-negative results. However, there is an increasing recognition that both clinical sensitivity and specificity of cervical cancer screening are important to patient safety and must be considered in the context of using current and future HPV DNA tests. Exquisite analytic sensitivity for HPV does not increase clinical sensitivity of an HPV test but does result in excessive test positivity and decreased clinical specificity. A recent US Food and Drug Administration (FDA)-approved HPV test, Cervista (Hologic, Bedford, MA), demonstrated excessive test positivity-2 to 4 times more positive than the other FDA-approved HPV test-from its premarketing approval trial. The poor specificity of Cervista raises questions about the safety and applicability of using this test in routine cervical cancer screening. These data provide a didactic example of the potential dangers of mistaking excellent analytic sensitivity and even clinical sensitivity for good clinical performance.
American Journal of Clinical Pathology 08/2010; 134(2):193-9. · 2.60 Impact Factor
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ABSTRACT: To estimate the relationship of human papillomavirus (HPV) detection and abnormal cytology with histologic diagnoses of cervical precancer and cancer.
From 2003 to 2008 we examined the HPV, cytology, and diagnostic results from almost one million cervical cancer screenings done on women aged 30 and older who were members in Kaiser Permanente Northern California, a large health maintenance organization that introduced cotesting in 2003. Women were screened using conventional Pap tests and a DNA test for a pool of 13 high-risk HPV genotypes. Women with HPV-positive atypical squamous cells of undetermined significance and other abnormal cervical cytology, independent of their HPV results, routinely underwent colposcopy. Results were stratified by 5-year age groups from 30 to 64.
High-grade squamous intraepithelial lesions (HSIL), atypical squamous cells, cannot exclude HSIL (ASC-H), and atypical glandular cells were more strongly associated with cervical intraepithelial neoplasia grade 3 while low-grade squamous intraepithelial lesions (LSIL) and HPV-positive atypical squamous cells of undetermined significance were more strongly associated with cervical intraepithelial neoplasia grade 2 (CIN2). Cervical cancer was most commonly found in women with HSIL and atypical glandular cells cytology. Human papillomavirus-negative women with ASC-H cytology were at a reduced but significant risk of CIN2 or more severe (CIN2+) (10.6%) compared with HPV-positive women with ASC-H cytology. Human papillomavirus-negative women with LSIL were at a 4.0% risk of CIN2+, and among women 50 and older, at a 0.5% risk of CIN2+ with no cancers were diagnosed.
Human papillomavirus testing may be useful for triage for colposcopic referral for LSIL cytology in older women but not for ASC-H cytology at any age.
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Obstetrics and Gynecology 07/2010; 116(1):76-84. · 4.73 Impact Factor
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ABSTRACT: To characterize the risks of cervical intraepithelial neoplasia 3 (CIN 3) and cancer in women aged 21 to 24 with human papillomavirus (HPV)-positive atypical squamous cells of undetermined significance (ASC-US) and low-grade squamous intraepithelial lesion (LSIL) screening results in routine clinical practice.
Quality assurance databases containing records of screening test and histologic findings from the Regional Laboratory of the Northern California Kaiser Permanente Medical Care Program were reviewed. Numbers of LSIL and HPV-positive ASC-US results and associated cancers and CIN 3 in women aged 21 to 24 during 2003 to 2007 were tabulated, and the corresponding risks were calculated overall and by year of age.
During the 5-year period from 2003 to 2007, 1,620 HPV-positive ASC-US and 2,175 LSIL were diagnosed in women aged 21 to 24, for which corresponding histologic finding is available. No invasive cancers were detected in association with LSIL and HPV-positive ASC-US screening results in this age group during this period. The risk of cancer was therefore 0% (95% CI = 0.00%-0.10%). The risk of CIN 3 associated with an HPV-positive ASC-US was 2.90% (95% CI = 2.14%-3.84%), with LSIL was 2.44% (95% CI = 1.83%-3.18%), and, for the 2 combined, the risk was 2.64% (95% CI = 2.15%-3.20%).
The risk of CIN 3 and cancer is low enough that management of women aged 21 to 24 with ASC-US and LSIL smears without immediate colposcopy should be considered, as is currently recommended for women aged 20 and younger.
Journal of Lower Genital Tract Disease 04/2010; 14(2):97-102. · 1.07 Impact Factor
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ABSTRACT: To quantify the age-specific and reproductive organ-specific cancer risk after an atypical glandular cell (AGC) cytologic interpretation in large clinic-based sample in which routine high-risk human papillomavirus (HPV) testing is conducted.
: To estimate the absolute risk of cervical precancer, cervical cancer, and endometrial cancer in women with AGC cytology, we conducted a cross-sectional study of women with AGC cytology (n=1,422) in a large health maintenance organization that introduced high-risk HPV DNA testing into cervical cancer screening in 2003. Risks and binomial exact 95% confidence intervals (CIs) of cervical intraepithelial neoplasia grade 2 or more severe (CIN 2 or worse) and endometrial cancer were calculated.
A total of 238 women with AGC cytology (16.7%, 95% CI 14.8-18.8%) were diagnosed with CIN 2 or worse, endometrial cancer, or other cancers. Among women aged 50 years or older, 420 high-risk HPV-negative women were at a 10.5% (95% CI 7.7-13.8%) risk of endometrial cancer, and 77 high-risk HPV-positive women were at a 10.4% (95% CI 4.6-19.4%) risk of cervical cancer and 0% (95% CI 0.0-4.7%) risk of endometrial cancer.
High-risk HPV testing may distinguish between risk of endometrial cancer and cervical cancer in women with AGC cervical cytology, particularly in women aged 50 years or older.
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Obstetrics and Gynecology 02/2010; 115(2 Pt 1):243-8. · 4.73 Impact Factor
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ABSTRACT: Cervical infections by approximately 15 cancer-associated (carcinogenic) human papillomavirus (HPV) genotypes cause virtually all cervical cancer and its immediate precursor lesions worldwide. Prophylactic vaccines against human papillomavirus (HPV) types HPV16 and HP18, which cause 70% of cervical cancer worldwide, hold great promise for reducing the burden of cervical cancer worldwide. However, current HPV vaccines prevent future infections and related cervical abnormalities and do not treat pre-existing HPV infections. In the U.S., HPV vaccine introduction should be considered in the context of a very successful cervical cancer screening program that has reduced the rates of cervical cancer by 75% or more. Thus, HPV vaccines will only prevent an incremental number of additional cervical cancers in the U.S. The introduction of HPV vaccines can also prevent other HPV-related sequelae, most importantly cervical intraepithelial neoplasia grade 2 or 3 (CIN2/3), which precede the development of cervical cancer and require clinical follow-up and treatment. Examining data from 7 clinical centers in the U.S., the median age of CIN2/3 is typically between 25 and 30 years of age in 2007; if screen-detected CIN2/3 develops on average 5-10 years after the causal infection is acquired, HPV vaccination will only prevent a significant proportion of CIN2/3 if it is given to women before the age of 26 and more so if given to women 18 and younger. It is increasingly evident that prophylactic HPV vaccines will provide the greatest public health or population benefit only when delivered to adolescent, mostly HPV-naive women.
Gynecologic Oncology 06/2009; 114(2):365-9. · 3.89 Impact Factor
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ABSTRACT: To estimate the 5-year age group-specific test positives for Pap tests and human papillomavirus (HPV) testing in a large, general screening population of women 30 and older.
Using data from Kaiser Permanente Northern California, a large health maintenance organization that introduced cotesting in 2003, we evaluated the cotesting results overall and by 5-year age groups. Women (n=580,289) who opted for and underwent cotesting (n cotests=812,598) between January 2003 and April 2008 were included in the analysis. Pap tests interpreted as atypical squamous cells of undetermined significance (ASC-US) or more severe were considered to be positive. Women were tested for carcinogenic HPV using an assay approved by the U.S. Food and Drug Administration. Binomial exact 95% confidence intervals (CIs) were calculated.
Overall, 6.27% (95% CI 6.21-6.32%) of cotests were carcinogenic HPV positive, and only 3.99% (95% CI 3.94-4.03%) cotests had normal cytology and were carcinogenic HPV positive. By comparison, 5.18% (95% CI 5.13-5.23%) of cotests had ASC-US or more severe cytology, and 2.87% (95% CI 2.84-2.91%) of cotests had ASC-US or more severe cytology and were carcinogenic HPV negative.
In a general screening population, concerns about excessive HPV test positives among women aged 30 years and older are not borne out.
Obstetrics and Gynecology 04/2009; 113(3):595-600. · 4.73 Impact Factor
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ABSTRACT: Recent studies have shown an association of loop electrocautery excision procedure (LEEP) with subsequent obstetric complications, including preterm birth. These data necessitate a reevaluation of how LEEP is used, particularly in cases where the presence of a high-grade lesion has not been established. In the 2001 consensus guidelines, nonadolescent women with high-grade cytology and subsequent negative colposcopy and endocervical curettage are recommended to undergo LEEP for further evaluation. Given the new information on potential obstetric complications and the rising age of childbearing, it is debatable whether the benefits of LEEP in this situation truly outweigh the risks for all women, regardless of age, who have not completed childbearing. We urge the committee charged with revising the guidelines to carefully consider this issue.
Journal of Lower Genital Tract Disease 05/2006; 10(2):109-10. · 1.07 Impact Factor
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ABSTRACT: To compare the risks of developing invasive squamous cell cervical cancer associated with screening intervals of 1, 2, and 3 years after a negative cervical smear. We conducted a matched case-control study of invasive squamous cell cervical cancer patients (n = 482) diagnosed between 1983 and 1995 among long-term members of a large health maintenance organization. Controls were matched for age, length of membership, and race (n = 934). Screening interval was time between the last negative cervical smear and the case diagnosis date. The main outcome measure was the relative odds of invasive disease associated with 1-year, 2-year, and 3-year intervals. The odds ratio for a 2-year versus a 1-year interval was 1.72 (95% confidence interval 1.12, 2.64, P =.013) and for a 3-year versus a 1-year interval was 2.06 (95% confidence interval 1.21, 3.50, P =.007). The odds ratio for a 3-year versus a 2-year interval was 1.20 (95% confidence interval 0.65, 2.21, P =.561). Controlling for ever having had an abnormal cervical smear or a previous consecutive negative smear did not substantially change these results. In this large health plan, the relative risks of invasive squamous cell cervical cancer were significantly greater for 2-year and 3-year cervical cancer screening intervals compared with a 1-year interval, but not for a 3-year interval compared with a 2-year interval. Our findings need to be placed in the context of the low absolute risks of developing invasive cervical cancer during the first 3 years after a negative cervical smear before making policy recommendation.
Obstetrics and Gynecology 02/2003; 101(1):29-37. · 4.73 Impact Factor
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ABSTRACT: The AHCPR released its evidence-based report, "Evaluation of Cervical Cytology" in early 1999. This report represents the most comprehensive analysis available to date of Pap smears and new technologies designed to improve cervical cancer screening. Both the ACOG and the AHCPR have released simplified summaries of the results of the evidence report that may lead to misunderstandings of the potential clinical impact of these new technologies. This report reviews the 4 major statements in these summaries and discusses how they are either incorrect based on the full AHCPR report or may be misinterpreted because their ramifications are not fully discussed. New screening technology has the potential to finally bring the sensitivity of a new Pap test to an acceptable level. The increased sensitivity afforded by these new technologies can reduce negative outcomes at reasonable cost-effectiveness ratios and at an equivalent or superior specificity compared to the conventional Pap smear.
Journal of Lower Genital Tract Disease 05/2001; 5(2):73-81. · 1.07 Impact Factor
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Debbie Saslow,
Philip E Castle,
J Thomas Cox,
Diane D Davey,
Mark H Einstein,
Daron G Ferris,
Sue J Goldie,
Diane M Harper, Walter Kinney,
Anna-Barbara Moscicki, [......],
Cosette M Wheeler,
Terri Ades,
Kimberly S Andrews,
Mary K Doroshenk,
Kelly Green Kahn,
Christy Schmidt,
Omar Shafey,
Robert A Smith,
Edward E Partridge,
Francisco Garcia
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ABSTRACT: The American Cancer Society (ACS) has developed guidelines for the use of the prophylactic human papillomavirus (HPV) vaccine for the prevention of cervical intraepithelial neoplasia and cervical cancer. These recommendations are based on a formal review of the available evidence. They address the use of prophylactic HPV vaccines, including who should be vaccinated and at what age, as well as a summary of policy and implementation issues. Implications for screening are also discussed.
CA A Cancer Journal for Clinicians 57(1):7-28. · 101.78 Impact Factor
