Mark Schiffman
National Institutes of Health
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CA: A Cancer Journal for Clinicians | 2012
Diane Solomon; Herschel W. Lawson; Maureen Killackey; Shalini L Kulasingam; Joanna M. Cain; Francisco Garcia; Ann T. Moriarty; Alan G. Waxman; David C. Wilbur; Nicolas Wentzensen; Levi S. Downs; Mark Spitzer; Anna-Barbara Moscicki; Eduardo L. Franco; Mark H. Stoler; Mark Schiffman; Philip E. Castle; Evan R. Myers
An update to the American Cancer Society (ACS) guideline regarding screening for the early detection of cervical precancerous lesions and cancer is presented. The guidelines are based on a systematic evidence review, contributions from 6 working groups, and a recent symposium cosponsored by the ACS, the American Society for Colposcopy and Cervical Pathology, and the American Society for Clinical Pathology, which was attended by 25 organizations. The new screening recommendations address age‐appropriate screening strategies, including the use of cytology and high‐risk human papillomavirus (HPV) testing, follow‐up (eg, the management of screen positives and screening intervals for screen negatives) of women after screening, the age at which to exit screening, future considerations regarding HPV testing alone as a primary screening approach, and screening strategies for women vaccinated against HPV16 and HPV18 infections. CA Cancer J Clin 2012.
Journal of the National Cancer Institute | 2013
Ahmedin Jemal; Edgar P. Simard; Christina Dorell; Anne-Michelle Noone; Lauri E. Markowitz; Betsy A. Kohler; Christie R. Eheman; Mona Saraiya; Priti Bandi; Kathleen A. Cronin; Meg Watson; Mark Schiffman; S. Jane Henley; Maria J. Schymura; Robert N. Anderson; David Yankey; Brenda K. Edwards
Background The American Cancer Society (ACS), the Centers for Disease Control and Prevention (CDC), the National Cancer Institute (NCI), and the North American Association of Central Cancer Registries (NAACCR) collaborate annually to provide updates on cancer incidence and death rates and trends in these outcomes for the United States. This year’s report includes incidence trends for human papillomavirus (HPV)–associated cancers and HPV vaccination (recommended for adolescents aged 11–12 years). Methods Data on cancer incidence were obtained from the CDC, NCI, and NAACCR, and data on mortality were obtained from the CDC. Long- (1975/1992–2009) and short-term (2000–2009) trends in age-standardized incidence and death rates for all cancers combined and for the leading cancers among men and among women were examined by joinpoint analysis. Prevalence of HPV vaccination coverage during 2008 and 2010 and of Papanicolaou (Pap) testing during 2010 were obtained from national surveys. Results Death rates continued to decline for all cancers combined for men and women of all major racial and ethnic groups and for most major cancer sites; rates for both sexes combined decreased by 1.5% per year from 2000 to 2009. Overall incidence rates decreased in men but stabilized in women. Incidence rates increased for two HPV-associated cancers (oropharynx, anus) and some cancers not associated with HPV (eg, liver, kidney, thyroid). Nationally, 32.0% (95% confidence interval [CI] = 30.3% to 33.6%) of girls aged 13 to 17 years in 2010 had received three doses of the HPV vaccine, and coverage was statistically significantly lower among the uninsured (14.1%, 95% CI = 9.4% to 20.6%) and in some Southern states (eg, 20.0% in Alabama [95% CI = 13.9% to 27.9%] and Mississippi [95% CI = 13.8% to 28.2%]), where cervical cancer rates were highest and recent Pap testing prevalence was the lowest. Conclusions The overall trends in declining cancer death rates continue. However, increases in incidence rates for some HPV-associated cancers and low vaccination coverage among adolescents underscore the need for additional prevention efforts for HPV-associated cancers, including efforts to increase vaccination coverage.
Proceedings of the National Academy of Sciences of the United States of America | 2013
Patrick J. Killela; Zachary J. Reitman; Yuchen Jiao; Chetan Bettegowda; Nishant Agrawal; Luis A. Diaz; Allan H. Friedman; Henry S. Friedman; Gary L. Gallia; Beppino C. Giovanella; Arthur P. Grollman; Tong-Chuan He; Yiping He; Ralph H. Hruban; George I. Jallo; Nils Mandahl; Alan K. Meeker; Fredrik Mertens; George J. Netto; B. Ahmed Rasheed; Gregory J. Riggins; Thomas A. Rosenquist; Mark Schiffman; Ie Ming Shih; Dan Theodorescu; Michael Torbenson; Victor E. Velculescu; Tian Li Wang; Nicolas Wentzensen; Laura D. Wood
Malignant cells, like all actively growing cells, must maintain their telomeres, but genetic mechanisms responsible for telomere maintenance in tumors have only recently been discovered. In particular, mutations of the telomere binding proteins alpha thalassemia/mental retardation syndrome X-linked (ATRX) or death-domain associated protein (DAXX) have been shown to underlie a telomere maintenance mechanism not involving telomerase (alternative lengthening of telomeres), and point mutations in the promoter of the telomerase reverse transcriptase (TERT) gene increase telomerase expression and have been shown to occur in melanomas and a small number of other tumors. To further define the tumor types in which this latter mechanism plays a role, we surveyed 1,230 tumors of 60 different types. We found that tumors could be divided into types with low (<15%) and high (≥15%) frequencies of TERT promoter mutations. The nine TERT-high tumor types almost always originated in tissues with relatively low rates of self renewal, including melanomas, liposarcomas, hepatocellular carcinomas, urothelial carcinomas, squamous cell carcinomas of the tongue, medulloblastomas, and subtypes of gliomas (including 83% of primary glioblastoma, the most common brain tumor type). TERT and ATRX mutations were mutually exclusive, suggesting that these two genetic mechanisms confer equivalent selective growth advantages. In addition to their implications for understanding the relationship between telomeres and tumorigenesis, TERT mutations provide a biomarker that may be useful for the early detection of urinary tract and liver tumors and aid in the classification and prognostication of brain tumors.
American Journal of Clinical Pathology | 2012
Diane Solomon; Herschel W. Lawson; Maureen Killackey; Shalini L Kulasingam; Joanna M. Cain; Francisco Garcia; Ann T. Moriarty; Alan G. Waxman; David C. Wilbur; Nicolas Wentzensen; Levi S. Downs; Mark Spitzer; Anna-Barbara Moscicki; Eduardo L. Franco; Mark H. Stoler; Mark Schiffman; Philip E. Castle; Evan R. Myers
An update to the American Cancer Society (ACS) guideline regarding screening for the early detection of cervical precancerous lesions and cancer is presented. The guidelines are based on a systematic evidence review, contributions from 6 working groups, and a recent symposium cosponsored by the ACS, the American Society for Colposcopy and Cervical Pathology, and the American Society for Clinical Pathology, which was attended by 25 organizations. The new screening recommendations address age-appropriate screening strategies, including the use of cytology and high-risk human papillomavirus (HPV) testing, follow-up (eg, the management of screen positives and screening intervals for screen negatives) of women after screening, the age at which to exit screening, future considerations regarding HPV testing alone as a primary screening approach, and screening strategies for women vaccinated against HPV16 and HPV18 infections.
American Journal of Obstetrics and Gynecology | 1995
J. Thomas Cox; Attila T. Lorincz; Mark Schiffman; Mark E. Sherman; Allison Cullen; Robert J. Kurman
Abstract OBJECTIVE: Our purpose was to determine the clinical value of human papillomavirus deoxyribonucleic acid testing with the hybrid capture test, specifically to examine whether human papillomavirus testing could identify which women with Papanicolaou smears read as atypical squamous cells of undetermined significance were most likely to have histologically confirmed cervical intraepithelial neoplasia. STUDY DESIGN: Hybrid capture testing for 14 human papillomavirus types, repeat Papanicolaou smears, and colposcopically directed biopsies were performed concurrently on 217 women referred to a student health colposcopy clinic with a previous Papanicolaou smear read as atypical squamous cells of undetermined significance. RESULTS: Human papillomavirus deoxyribonucleic acid positivity was associated with an eightfold increased likelihood of histologic confirmation of cervical intraepithelial neoplasia. The sensitivity of hybrid capture for any cervical intraepithelial neoplasia was 86% (4350) and for grade 2 or 3 was 93% (1415), whereas the corresponding values for the repeat Papanicolaou smear were 60% (3050) and 73% (1115), respectively. Moreover, high viral levels of human papillomavirus types known to be associated with cervical cancer were strongly predictive of high-grade cervical intraepithelial neoplasia. CONCLUSIONS: Testing for human papillomavirus deoxyribonucleic acid with hybrid capture appears to offer an effective means by which patients whose cervical Papanicolaou smears have been read as atypical squamous cells of undetermined significance could be triaged for colposcopy. In particular, sensitivity for high-grade cervical intraopithelial neoplasia could be maintained and specificity markedly improved by referring only those patients who had elevated levels of human papillomavirus deoxyribonucleic acid of cancer-associated viral types.
Journal of the National Cancer Institute | 2011
Mark Schiffman; Nicolas Wentzensen; Sholom Wacholder; Walter Kinney; Julia C. Gage; Philip E. Castle
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.
Lancet Oncology | 2011
Hormuzd A. Katki; Walter Kinney; Barbara Fetterman; Thomas Lorey; Nancy E. Poitras; Li C. Cheung; Franklin Demuth; Mark Schiffman; Sholom Wacholder; Philip E. Castle
BACKGROUND Concurrent testing for human papillomavirus (HPV) and cervical cytology (co-testing) is an approved alternative to cytology alone in women aged 30 years and older. We aimed to assess the safety in routine clinical practice of 3-year screening intervals for women testing negative for HPV with normal cytology and to assess if co-testing can identify women at high risk of cervical cancer or cervical intraepithelial neoplasia grade 3 (CIN3) or worse over 5 years. METHODS We assessed the 5-year cumulative incidence, starting in 2003-05, of cervical cancer and CIN3 or worse for 331,818 women aged 30 years and older who enrolled in co-testing at Kaiser Permanente Northern California (Berkeley, CA, USA) and had adequate enrolment co-test results. Follow-up continued until Dec 31, 2009. We defined cumulative incidence to include prevalence at enrolment and incidence after enrolment. Prevalence at enrolment was defined as the ratio of women diagnosed with each outcome on the biopsy visit immediately after their enrolment screening visit to the total enrolled women. At screening visits only HPV test and Pap smear samples were collected, and at biopsy visits colposcopically directed biopsies were taken. To estimate post-enrolment incidence, we used Weibull survival models. FINDINGS In 315,061 women negative by HPV testing, the 5-year cumulative incidence of cancer was 3.8 per 100,000 women per year, slightly higher than for the 306,969 who were both negative by HPV and Pap testing (3.2 per 100,000), and half the cancer risk of the 319,177 who were negative by Pap testing (7.5 per 100,000). 313,465 (99.5%) women negative by HPV testing had either normal cytology or equivocal abnormalities. Abnormal cytology greatly increased cumulative incidence of CIN3 or worse over 5 years for the 16,757 positive by HPV testing (12.1%vs 5.9%; p<0.0001). By contrast, although statistically significant, abnormal cytology did not increase 5-year risk of CIN3 or worse for women negative by HPV testing to a substantial level (0.86%vs 0.16%; p=0.004). 12,208 (73%) of the women positive by HPV testing had no cytological abnormality, and these women had 258 (35%) of 747 CIN3 or adenocarcinoma in situ, [corrected] 25 (29%) of 87 cancers, and 17 (63%) of 27 adenocarcinomas. INTERPRETATION For women aged 30 years and older in routine clinical practice who are negative by co-testing (both HPV and cytology), 3-year screening intervals were safe because a single negative test for HPV was sufficient to reassure against cervical cancer over 5 years. Incorporating HPV testing with cytology also resulted in earlier identification of women at high risk of cervical cancer, especially adenocarcinoma. Testing for HPV without adjunctive cytology might be sufficiently sensitive for primary screening for cervical cancer. FUNDING Intramural Research Program of the US National Cancer Institute/NIH/DHHS, and the American Cancer Society.
British Journal of Cancer | 1999
Debra T. Silverman; Mark Schiffman; J. Everhart; Alisa M. Goldstein; Keith D. Lillemoe; G. M. Swanson; Ann G. Schwartz; Linda Morris Brown; Raymond S. Greenberg; Janet B. Schoenberg; Linda M. Pottern; Robert N. Hoover; Joseph F. Fraumeni
SummaryIn a population-based case-control study of pancreatic cancer conducted in three areas of the USA, 484 cases and 2099 controls were interviewed to evaluate the aetiologic role of several medical conditions/interventions, including diabetes mellitus, cholecystectomy, ulcer/gastrectomy and allergic states. We also evaluated risk associated with family history of cancer. Our findings support previous studies indicating that diabetes is a risk factor for pancreatic cancer, as well as a possible complication of the tumour. A significant positive trend in risk with increasing years prior to diagnosis of pancreatic cancer was apparent (P-value for test of trend = 0.016), with diabetics diagnosed at least 10 years prior to diagnosis having a significant 50% increased risk. Those treated with insulin had risks similar to those not treated with insulin (odds ratio (OR) = 1.6 and 1.5 respectively), and no trend in risk was associated with increasing duration of insulin treatment. Cholecystectomy also appeared to be a risk factor, as well as a consequence of the malignancy. Subjects with a cholecystectomy at least 20 years prior to the diagnosis of pancreatic cancer experienced a 70% increased risk, which was marginally significant. In contrast, subjects with a history of duodenal or gastric ulcer had little or no elevated risk (OR = 1.2; confidence interval = 0.9–1.6). Those treated by gastrectomy had the same risk as those not receiving surgery, providing little support for the hypothesis that gastrectomy is a risk factor for pancreatic cancer. A significant 40% reduced risk was associated with hay fever, a non-significant 50% decreased risk with allergies to animals, and a non-significant 40% reduced risk with allergies to dust/moulds. These associations, however, may be due to chance since no risk reductions were apparent for asthma or several other types of allergies. In addition, we observed significantly increased risks for subjects reporting a first-degree relative with cancers of the pancreas (OR = 3.2), colon (OR = 1.7) or ovary (OR = 5.3) and non-significantly increased risks for cancers of the endometrium (OR = 1.5) or breast (OR = 1.3). The pattern is consistent with the familial predisposition reported for pancreatic cancer and with the array of tumours associated with hereditary non-polyposis colon cancer.
The Journal of Infectious Diseases | 2005
Rolando Herrero; Philip E. Castle; Mark Schiffman; M. Concepcion Bratti; Allan Hildesheim; Jorge Morales; Mario Alfaro; Mark E. Sherman; Sholom Wacholder; Sabrina Chen; Ana Cecilia Rodriguez; Robert D. Burk
BACKGROUND Detailed epidemiologic studies of cervical type-specific human papillomavirus (HPV) infection in large populations are scarce. METHODS We recruited a population-based cohort in Guanacaste, Costa Rica. Participants were interviewed, screened for cervical neoplasia, and tested for >40 HPV types by use of MY09/11 L1 consensus primer polymerase chain reaction. We estimated the risk factors for infection and the associations between type-specific HPV infections and cervical intraepithelial neoplasia (CIN) and cancer in 8514 sexually active women who had not undergone a hysterectomy. RESULTS The overall HPV prevalence was 26.5%. The most common type was HPV-16 (3.6% of the population). HPV prevalence showed a U-shaped age-specific curve. Sexual behaviors were the main determinants of oncogenic and nononcogenic infections; age at first sexual intercourse was not independently associated with infection. Barrier contraceptive use was somewhat protective against infection. Oncogenic infections were strongly associated with risk of all grades of CIN and of cancer. Types 16, 18, and 58 were the most common in women diagnosed with CIN3 and cancer. Except for those that included HPV-16, multiple-type infections were associated with an increased risk (compared with that for single-type infections) of all grades of CIN and of cancer. CONCLUSIONS We confirmed the bimodal age pattern of HPV infection in Guanacaste and the sexually transmitted nature of both oncogenic and nononcogenic HPV types.
The Journal of Infectious Diseases | 2005
Philip E. Castle; Mark Schiffman; Rolando Herrero; Allan Hildesheim; Ana Cecilia Rodriguez; M. Concepcion Bratti; Mark E. Sherman; Sholom Wacholder; Robert E. Tarone; Robert D. Burk
BACKGROUND Cross-sectional human papillomavirus (HPV) DNA prevalence peaks at young ages, reflecting sexual acquisition and typically rapid clearance. In some populations, HPV prevalence demonstrates a second peak in older women. Longitudinal data may help to explain this second peak. METHODS We followed a population-based cohort of 7237 women in Guanacaste, Costa Rica, in which we had previously observed a second peak in the baseline HPV prevalence in older women. We tested for >40 HPV types by polymerase chain reaction. We analyzed age-specific patterns of acquisition and persistence 5-7 years after enrollment for individual HPV types. RESULTS At enrollment and follow-up, cross-sectional data revealed U-shaped age-specific HPV prevalence curves for virtually every type, with higher prevalences in the younger and older women than in the middle-aged women. Prospectively, acquisition of types decreased significantly as women aged (PTrend<.05, for both), with the highest peak in young women and a secondary minor peak in older women. Type-specific persistence of HPV increased with age (PTrend<.0001). Overall, HPV acquisition predominated at younger ages, whereas persistent infections gradually became more prominent with age (PTrend<.0001). CONCLUSIONS Newly apparent infections decreased, whereas persistence increased, with age; this latter tendency supports the utility of HPV screening in older women.