Description of Evidence
A study using data from a population-based randomized trial of cervical screening among women aged 32 to 38 years compared 11 different screening strategies using HPV DNA testing and cytology. The strategy of initial screening with an HPV DNA test and a triage of HPV-positive results with cytology, and subsequent repeat HPV DNA testing after 1 year for women who were HPV positive but cytology negative, increased the sensitivity for detection of CIN 3+ by 30% compared with cytology alone, and increased the total number of screening tests performed by only 12%.
Screening Benefit According to Age
Cervical cancer mortality, usually occurring among unscreened women, increases with age, with the maximum mortality for white women between age 45 years and 70 years, and for black women in their 70s.[57,70] (Also available online.) Mortality among women with negative Pap screening is low at all ages.
Screening by Pap testing with associated diagnostic testing and treatment is effective in reducing the incidence of all histologies and stages of invasive cervical cancer. The benefit increases with age. Whereas the odds ratio (OR) is 0.79 (95% CI, 0.57-1.1) among women screened at age 30 to 31 years for developing cancer at age 35 to 39 years, it improves to 0.26 (95% CI, 0.19-0.36) among women screened at age 52 to 54 years for developing cancer at age 55 to 59 years.
Women aged 20 to 24 years are those most likely to have Pap abnormalities leading to further testing and treatment (refer to the Evidence of Harm section of this summary for more information), so forgoing Pap testing in these women may improve the benefit-risk balance for this intervention.
HSIL are rare among women older than 65 years who have been previously screened. For women with a negative Pap test at age 60 years and older, the likelihood of having a new diagnosis of CIN 3+ on repeat screening is less than 1 in 1,000 (in some studies, as few as 2-6 in 10,000).
- American Cancer Society.: Cancer Facts and Figures 2011. Atlanta, Ga: American Cancer Society, 2011. Also available online. Last accessed July 27, 2011.
- Solomon D, Davey D, Kurman R, et al.: The 2001 Bethesda System: terminology for reporting results of cervical cytology. JAMA 287 (16): 2114-9, 2002.
- Holowaty P, Miller AB, Rohan T, et al.: Natural history of dysplasia of the uterine cervix. J Natl Cancer Inst 91 (3): 252-8, 1999.
- Nasiell K, Roger V, Nasiell M: Behavior of mild cervical dysplasia during long-term follow-up. Obstet Gynecol 67 (5): 665-9, 1986.
- Nash JD, Burke TW, Hoskins WJ: Biologic course of cervical human papillomavirus infection. Obstet Gynecol 69 (2): 160-2, 1987.
- Melnikow J, Nuovo J, Willan AR, et al.: Natural history of cervical squamous intraepithelial lesions: a meta-analysis. Obstet Gynecol 92 (4 Pt 2): 727-35, 1998.
- Berrington de Gonz�lez A, Green J; International Collaboration of Epidemiological Studies of Cervical Cancer.: Comparison of risk factors for invasive squamous cell carcinoma and adenocarcinoma of the cervix: collaborative reanalysis of individual data on 8,097 women with squamous cell carcinoma and 1,374 women with adenocarcinoma from 12 epidemiological studies. Int J Cancer 120 (4): 885-91, 2007.
- Bosch FX, Manos MM, Mu�oz N, et al.: Prevalence of human papillomavirus in cervical cancer: a worldwide perspective. International biological study on cervical cancer (IBSCC) Study Group. J Natl Cancer Inst 87 (11): 796-802, 1995.
- Wallin KL, Wiklund F, Angstr�m T, et al.: Type-specific persistence of human papillomavirus DNA before the development of invasive cervical cancer. N Engl J Med 341 (22): 1633-8, 1999.
- Alani RM, M�nger K: Human papillomaviruses and associated malignancies. J Clin Oncol 16 (1): 330-7, 1998.
- Walboomers JM, Jacobs MV, Manos MM, et al.: Human papillomavirus is a necessary cause of invasive cervical cancer worldwide. J Pathol 189 (1): 12-9, 1999.
- Ho GY, Bierman R, Beardsley L, et al.: Natural history of cervicovaginal papillomavirus infection in young women. N Engl J Med 338 (7): 423-8, 1998.
- Howlader N, Noone AM, Krapcho M, et al., eds.: SEER Cancer Statistics Review, 1975-2008. Bethesda, Md: National Cancer Institute, 2011. Also available online. Last accessed July 11, 2011.
- Arends MJ, Buckley CH, Wells M: Aetiology, pathogenesis, and pathology of cervical neoplasia. J Clin Pathol 51 (2): 96-103, 1998.
- Ries LA, Eisner MP, Kosary CL, et al.: SEER Cancer Statistics Review, 1973-1999. Bethesda, Md: National Cancer Institute, 2002. Also available online. Last accessed April 21, 2011.
- L??r? E, Day NE, Hakama M: Trends in mortality from cervical cancer in the Nordic countries: association with organised screening programmes. Lancet 1 (8544): 1247-9, 1987.
- Christopherson WM, Lundin FE Jr, Mendez WM, et al.: Cervical cancer control: a study of morbidity and mortality trends over a twenty-one-year period. Cancer 38 (3): 1357-66, 1976.
- Miller AB, Lindsay J, Hill GB: Mortality from cancer of the uterus in Canada and its relationship to screening for cancer of the cervix. Int J Cancer 17 (5): 602-12, 1976.
- Johannesson G, Geirsson G, Day N: The effect of mass screening in Iceland, 1965-74, on the incidence and mortality of cervical carcinoma. Int J Cancer 21 (4): 418-25, 1978.
- Sigurdsson K: Effect of organized screening on the risk of cervical cancer. Evaluation of screening activity in Iceland, 1964-1991. Int J Cancer 54 (4): 563-70, 1993.
- Benedet JL, Anderson GH, Matisic JP: A comprehensive program for cervical cancer detection and management. Am J Obstet Gynecol 166 (4): 1254-9, 1992.
- Aristizabal N, Cuello C, Correa P, et al.: The impact of vaginal cytology on cervical cancer risks in Cali, Colombia. Int J Cancer 34 (1): 5-9, 1984.
- Clarke EA, Anderson TW: Does screening by "Pap" smears help prevent cervical cancer? A case-control study. Lancet 2 (8132): 1-4, 1979.
- La Vecchia C, Franceschi S, Decarli A, et al.: "Pap" smear and the risk of cervical neoplasia: quantitative estimates from a case-control study. Lancet 2 (8406): 779-82, 1984.
- Herrero R, Brinton LA, Reeves WC, et al.: Screening for cervical cancer in Latin America: a case-control study. Int J Epidemiol 21 (6): 1050-6, 1992.
- Celentano DD, Klassen AC, Weisman CS, et al.: Duration of relative protection of screening for cervical cancer. Prev Med 18 (4): 411-22, 1989.
- Screening for squamous cervical cancer: duration of low risk after negative results of cervical cytology and its implication for screening policies. IARC Working Group on evaluation of cervical cancer screening programmes. Br Med J (Clin Res Ed) 293 (6548): 659-64, 1986.
- Kleinman JC, Kopstein A: Who is being screened for cervical cancer? Am J Public Health 71 (1): 73-6, 1981.
- Sankaranarayanan R, Esmy PO, Rajkumar R, et al.: Effect of visual screening on cervical cancer incidence and mortality in Tamil Nadu, India: a cluster-randomised trial. Lancet 370 (9585): 398-406, 2007.
- Sankaranarayanan R, Nene BM, Shastri SS, et al.: HPV screening for cervical cancer in rural India. N Engl J Med 360 (14): 1385-94, 2009.
- Szarewski A: Cervical screening by visual inspection with acetic acid. Lancet 370 (9585): 365-6, 2007.
- Brewster WR, Hubbell FA, Largent J, et al.: Feasibility of management of high-grade cervical lesions in a single visit: a randomized controlled trial. JAMA 294 (17): 2182-7, 2005.
- Denny L, Kuhn L, De Souza M, et al.: Screen-and-treat approaches for cervical cancer prevention in low-resource settings: a randomized controlled trial. JAMA 294 (17): 2173-81, 2005.
- Soost HJ, Lange HJ, Lehmacher W, et al.: The validation of cervical cytology. Sensitivity, specificity and predictive values. Acta Cytol 35 (1): 8-14, 1991 Jan-Feb.
- Benoit AG, Krepart GV, Lotocki RJ: Results of prior cytologic screening in patients with a diagnosis of Stage I carcinoma of the cervix. Am J Obstet Gynecol 148 (5): 690-4, 1984.
- Nanda K, McCrory DC, Myers ER, et al.: Accuracy of the Papanicolaou test in screening for and follow-up of cervical cytologic abnormalities: a systematic review. Ann Intern Med 132 (10): 810-9, 2000.
- Martin-Hirsch P, Lilford R, Jarvis G, et al.: Efficacy of cervical-smear collection devices: a systematic review and meta-analysis. Lancet 354 (9192): 1763-70, 1999.
- Hartmann KE, Hall SA, Nanda K, et al.: Screening for Cervical Cancer. Rockville, Md: Agency for Health Research and Quality, 2002. Available online. Last accessed April 21, 2011.
- McCrory DC, Matchar DB, Bastian L, et al.: Evaluation of Cervical Cytology. Rockville, Md: Agency for Health Research and Quality, 1999. Evidence Report/Technology Assessment No. 5. AHCPR Publication No. 99-E010. Also available online. Last accessed April 21, 2011.
- Coste J, Cochand-Priollet B, de Cremoux P, et al.: Cross sectional study of conventional cervical smear, monolayer cytology, and human papillomavirus DNA testing for cervical cancer screening. BMJ 326 (7392): 733, 2003.
- Fox J, Remington P, Layde P, et al.: The effect of hysterectomy on the risk of an abnormal screening Papanicolaou test result. Am J Obstet Gynecol 180 (5): 1104-9, 1999.
- Pearce KF, Haefner HK, Sarwar SF, et al.: Cytopathological findings on vaginal Papanicolaou smears after hysterectomy for benign gynecologic disease. N Engl J Med 335 (21): 1559-62, 1996.
- Sawaya GF, Grady D, Kerlikowske K, et al.: The positive predictive value of cervical smears in previously screened postmenopausal women: the Heart and Estrogen/progestin Replacement Study (HERS). Ann Intern Med 133 (12): 942-50, 2000.
- Sawaya GF, McConnell KJ, Kulasingam SL, et al.: Risk of cervical cancer associated with extending the interval between cervical-cancer screenings. N Engl J Med 349 (16): 1501-9, 2003.
- Creighton P, Lew JB, Clements M, et al.: Cervical cancer screening in Australia: modelled evaluation of the impact of changing the recommended interval from two to three years. BMC Public Health 10: 734, 2010.
- McCredie MR, Sharples KJ, Paul C, et al.: Natural history of cervical neoplasia and risk of invasive cancer in women with cervical intraepithelial neoplasia 3: a retrospective cohort study. Lancet Oncol 9 (5): 425-34, 2008.
- Stoler MH, Schiffman M; Atypical Squamous Cells of Undetermined Significance-Low-grade Squamous Intraepithelial Lesion Triage Study (ALTS) Group.: Interobserver reproducibility of cervical cytologic and histologic interpretations: realistic estimates from the ASCUS-LSIL Triage Study. JAMA 285 (11): 1500-5, 2001.
- Castle PE, Schiffman M, Wheeler CM, et al.: Evidence for frequent regression of cervical intraepithelial neoplasia-grade 2. Obstet Gynecol 113 (1): 18-25, 2009.
- Carozzi FM, Del Mistro A, Confortini M, et al.: Reproducibility of HPV DNA Testing by Hybrid Capture 2 in a Screening Setting. Am J Clin Pathol 124 (5): 716-21, 2005.
- New Device Approval: Digene Hybrid Capture 2 High-Risk HPV DNA Test - P890064 S009 A004 . Rockville, Md: U.S. Food and Drug Administration, Center for Devices and Radiological Health, 2003. Available Online. Last accessed April 21, 2011.
- Kulasingam SL, Kim JJ, Lawrence WF, et al.: Cost-effectiveness analysis based on the atypical squamous cells of undetermined significance/low-grade squamous intraepithelial lesion Triage Study (ALTS). J Natl Cancer Inst 98 (2): 92-100, 2006.
- ASCUS-LSIL Traige Study (ALTS) Group.: Results of a randomized trial on the management of cytology interpretations of atypical squamous cells of undetermined significance. Am J Obstet Gynecol 188 (6): 1383-92, 2003.
- Wright TC Jr, Massad LS, Dunton CJ, et al.: 2006 consensus guidelines for the management of women with abnormal cervical cancer screening tests. Am J Obstet Gynecol 197 (4): 346-55, 2007.
- Sherman ME, Schiffman M, Cox JT, et al.: Effects of age and human papilloma viral load on colposcopy triage: data from the randomized Atypical Squamous Cells of Undetermined Significance/Low-Grade Squamous Intraepithelial Lesion Triage Study (ALTS). J Natl Cancer Inst 94 (2): 102-7, 2002.
- ASCUS-LSIL Traige Study (ALTS) Group.: A randomized trial on the management of low-grade squamous intraepithelial lesion cytology interpretations. Am J Obstet Gynecol 188 (6): 1393-400, 2003.
- Zuna RE, Wang SS, Rosenthal DL, et al.: Determinants of human papillomavirus-negative, low-grade squamous intraepithelial lesions in the atypical squamous cells of undetermined significance/low-grade squamous intraepithelial lesions triage study (ALTS). Cancer 105 (5): 253-62, 2005.
- Saslow D, Runowicz CD, Solomon D, et al.: American Cancer Society guideline for the early detection of cervical neoplasia and cancer. CA Cancer J Clin 52 (6): 342-62, 2002 Nov-Dec.
- Goldie SJ, Kim JJ, Wright TC: Cost-effectiveness of human papillomavirus DNA testing for cervical cancer screening in women aged 30 years or more. Obstet Gynecol 103 (4): 619-31, 2004.
- Arbyn M, Sasieni P, Meijer CJ, et al.: Chapter 9: Clinical applications of HPV testing: a summary of meta-analyses. Vaccine 24 (Suppl 3): S3/78-89, 2006.
- Mayrand MH, Duarte-Franco E, Rodrigues I, et al.: Human papillomavirus DNA versus Papanicolaou screening tests for cervical cancer. N Engl J Med 357 (16): 1579-88, 2007.
- Naucler P, Ryd W, T�rnberg S, et al.: Human papillomavirus and Papanicolaou tests to screen for cervical cancer. N Engl J Med 357 (16): 1589-97, 2007.
- Bulkmans NW, Berkhof J, Rozendaal L, et al.: Human papillomavirus DNA testing for the detection of cervical intraepithelial neoplasia grade 3 and cancer: 5-year follow-up of a randomised controlled implementation trial. Lancet 370 (9601): 1764-72, 2007.
- Cuzick J, Szarewski A, Cubie H, et al.: Management of women who test positive for high-risk types of human papillomavirus: the HART study. Lancet 362 (9399): 1871-6, 2003.
- Cuzick J, Clavel C, Petry KU, et al.: Overview of the European and North American studies on HPV testing in primary cervical cancer screening. Int J Cancer 119 (5): 1095-101, 2006.
- Carozzi F, Confortini M, Dalla Palma P, et al.: Use of p16-INK4A overexpression to increase the specificity of human papillomavirus testing: a nested substudy of the NTCC randomised controlled trial. Lancet Oncol 9 (10): 937-45, 2008.
- Koshiol J, Lindsay L, Pimenta JM, et al.: Persistent human papillomavirus infection and cervical neoplasia: a systematic review and meta-analysis. Am J Epidemiol 168 (2): 123-37, 2008.
- Castle PE: Invited commentary: is monitoring of human papillomavirus infection for viral persistence ready for use in cervical cancer screening? Am J Epidemiol 168 (2): 138-44; discussion 145-8, 2008.
- Ronco G, Giorgi-Rossi P, Carozzi F, et al.: Efficacy of human papillomavirus testing for the detection of invasive cervical cancers and cervical intraepithelial neoplasia: a randomised controlled trial. Lancet Oncol 11 (3): 249-57, 2010.
- Naucler P, Ryd W, T�rnberg S, et al.: Efficacy of HPV DNA testing with cytology triage and/or repeat HPV DNA testing in primary cervical cancer screening. J Natl Cancer Inst 101 (2): 88-99, 2009.
- National Institutes of Health Consensus Development Conference Statement: cervical cancer, April 1-3, 1996. National Institutes of Health Consensus Development Panel. J Natl Cancer Inst Monogr (21): vii-xix, 1996.
- Sasieni P, Castanon A, Cuzick J: Effectiveness of cervical screening with age: population based case-control study of prospectively recorded data. BMJ 339: b2968, 2009.