HUMAN PAPILLOMAVIRUS (HPV) TESTING

Transcription

1 MEDICAL POLICY HUMAN PAPILLOMAVIRUS (HPV) TESTING Policy Number: CDP Effective Date: October 1, 2014 Table of Contents Page BACKGROUND 1 POLICY 3 REFERENCES 5 POLICY HISTORY/REVISION HISTORY 7 INSTRUCTIONS FOR USE This Medical Policy provides assistance in interpreting UnitedHealthcare benefit plans. When deciding coverage, the enrollee specific document must be referenced. The terms of an enrollee's document (e.g., Certificate of Coverage (COC) or Summary Plan Description (SPD)) may differ greatly. In the event of a conflict, the enrollee's specific benefit document supersedes this Medical Policy. All reviewers must first identify enrollee eligibility, any federal or state regulatory requirements and the plan benefit coverage prior to use of this Medical Policy. Other Policies and Coverage Determination Guidelines may apply. UnitedHealthcare reserves the right, in its sole discretion, to modify its Policies and Guidelines as necessary. This Medical Policy is provided for informational purposes. It does not constitute medical advice. UnitedHealthcare may also use tools developed by third parties, such as the MCG Care Guidelines, to assist us in administering health benefits. The MCG Care Guidelines are intended to be used in connection with the independent professional medical judgment of a qualified health care provider and do not constitute the practice of medicine or medical advice. BACKGROUND Cervical cancer slowly progresses as the normal cervical cells gradually develop precancerous changes, defined as cervical intraepithelial neoplasia (CIN), squamous intraepithelial lesion (SIL), or dysplasia. These precancerous changes have the potential to turn into cancer if left untreated. 1 There are two main types of cervical cancer including squamous cell carcinoma (80-90%) and adenocarcinoma (10-20%). 1 Human Papillomavirus (HPV), a sexually transmitted infection, has been strongly linked to cervical cancer. Infection with HPV is common and in most women the body is able to clear the infection on its own. At young ages and at the most sexually active ages, the great majority of infected women (more than 90%) have transient infections that resolve spontaneously without producing symptoms or cellular changes. 2-5 Sometimes, however, in a small fraction of women the infection persists and becomes chronic. 3 It is this small group of women, chronic carriers of certain HPV types, who have a high risk of disease progression and development of neoplastic lesions of the anogenital tract. 6 Overall, there are more than 100 different HPV that infect the surfaces of the skin, genitals, anus, mouth and throat. 1 Many of these viruses are low risk and cause papillomas (warts), like HPV 6 or HPV 11 that cause genital warts. Some HPV genotypes are considered high-risk as they are linked to certain cancers including Proprietary Information of UnitedHealthcare. Copyright 2014 United HealthCare Services, Inc. Page 1

2 cancer of the cervix, vulva, and vagina in women, penile cancer in men and anal and oral cancer in both men and women. 1 The most common high risk types include HPV 16, 18, 31, 33, and 45. Between % of squamous cell carcinomas contain DNA from high risk types of HPV and HPV 16 and 18 are implicated in twothirds of all cervical cancers. 1,2,7,8 HPV DNA testing is performed on residual exfoliated cervical cells from a liquid-based cytology or specimen transport medium. If the sample is not in conjunction with a Pap cytology specimen, it is collected similarly. Based on the central role of persistent, high risk HPV in cervical cancer, HPV testing has recently been introduced into cervical cancer screening algorithms. High-risk HPV testing has proven greater reproducibility and greater sensitivity for detection of cervical pre-cancer and cancer than cytology Furthermore, high sensitivity has been repeatedly demonstrated While the Pap test detects cellular changes in cervical cells caused by HPV infection; the newer molecular based tests look for the infections themselves by finding DNA and RNA from HPV in the cells. According to a risk stratification article by Castle et al, the addition of more accurate methods of screening and diagnosis such as HPV testing could increase both the sensitivity and efficiency of the cervical cancer screening process. 20 HPV testing has the ability to detect 25-50% of lesions missed by a single cytology screen. 21 HPV Testing Currently in the US, the use of HPV testing as a primary screening method for cervical cancer is not approved by the FDA. However, there is interest in using the HPV test as a triage test to stratify risk of women age 21 and older with atypical squamous cells of undetermined significance (ASC-US) cytology and post-menopausal women with low grade squamous intraepithelial lesion (LSIL) cytology. 17,18,19b Additionally, HPV testing has also become an adjunct to cytology for primary screening for certain age groups. HPV DNA testing in women over the age of 21 is an effective way to triage ASC-US cytology. 10,21-26 Arbyn et al completed a 20 study meta-analysis to determine the efficacy of HPV DNA testing for use in ASC-US triage. 10 The overall results demonstrated a sensitivity of 92.5% to detect CIN2+ (high-grade CIN) with a specificity of 62.5%. Likewise, for detecting CIN3+, the sensitivity was 95.6% with a specificity of 59.2%. Concurrent testing for HPV and cervical cytology (co-testing) is an acceptable alternative to cytology alone in women 30+ years. 21 In routine clinical practice for women 30+ years of age who are negative by co-testing, Katki et al, demonstrated that 3 year screening intervals are safe because a single negative test for HPV was sufficient to reassure against cervical cancer over 5 years. 27 In screening studies in North American and Europe, the pooled sensitivity and specificity of HPV testing for the detection of CIN2+ in women 35 years and older is 95% and 93%, respectively. 9 For comparison, pooled sensitivity and specificity of cytology at a threshold of ASC-US are 60% and 97%, respectively. Sensitivity using a combination of HPV and cytology is significantly higher than that of either test alone with NPVs of %. 9,17 Recently, the ATHENA (Addressing THE Need for Advanced HPV Diagnostics) HPV study evaluated the clinical usefulness of the cobas HPV test (Roche Molecular Systems, Pleasanton, CA) for high-risk HPV testing (14 highrisk types) and individual HPV-16/HPV-18 genotyping in women undergoing routine cervical cytology screening the US. 28 In over 30,000 women age 30 years or older with NILM cytology, the prevalence of high-risk HPV overall was 6.7% and this study demonstrated that high-risk HPV status is an important predictor of the current and future detection of CIN2+ in women with NILM cytology. Proprietary Information of UnitedHealthcare. Copyright 2014 United HealthCare Services, Inc. Page 2

3 It has also been demonstrated in several studies that women with negative HPV and cytology results have a lower risk of developing CIN 2+ than women with only a negative cytology test. 10,16-18,26 In a study of Danish women age years of age with 10 years of follow up, less than 2% of cytology negative and HPV negative women developed CIN Similar results have been reported in women aged 30 years or older in Portland, OR. 30 Society Guidelines American Society for Colposcopy and Cervical Pathology(ASCCP), American Cancer Society (ACS), American Society of Clinical Pathology (ASCP) 19 These following are current 2012 evidence-based guidelines from the American Society for Colposcopy and Cervical Pathology (ASCCP), American Cancer Society (ACS), American Society of Clinical Pathology (ASCP), and Preventive Services Task Force (USPSTF), and are supported by the American College of Obstetrics and Gynecologists (ACOG). Screening Co-testing with cytology is the preferred screening strategy for women aged years For women aged years, with negative cytology results but with absent or insufficient transformation zone component and no or unknown HPV test results, HPV testing is preferred Management For women aged 25 and above with ASC-US cytology, reflex HPV testing is preferred For women aged years with ASC-US, reflex HPV testing is acceptable) Acceptable options for the management of postmenopausal women with LSIL and no HPV test include obtaining HPV testing POLICY For the following CPT code(s) in Table 1, the patient should have a diagnosis (ICD- 9-CM) code(s) listed in Table 2. Table 1. HCPCS Codes (Alphanumeric, CPT AMA) HCPCS Code Description Papillomavirus, human, amplified probe technique Table 2. ICD-9-CM Codes Covered ICD-9 Code Description 42 Human immunodeficiency virus [HIV] disease Proprietary Information of UnitedHealthcare. Copyright 2014 United HealthCare Services, Inc. Page 3

4 ICD-9 Code Description Human papillomavirus in conditions classified elsewhere and of 79.4 unspecified site Malignant neoplasm of lip, oral cavity, and pharynx Dysplasia of cervix, unspecified Mild dysplasia of cervix Other specified noninflammatory disorders of cervix 623 Dysplasia of vagina 795 Abnormal glandular papanicolaou smear of cervix Papanicolaou smear of cervix with atypical squamous cells of undetermined significance (ASC-US) Papanicolaou smear of cervix with atypical squamous cells cannot exclude high grade squamous intraepithelial lesion (ASC-H) Papanicolaou smear of cervix with low grade squamous intraepithelial lesion (LGSIL) Cervical high risk human papillomavirus (HPV) DNA test positive Other abnormal Papanicolaou smear of cervix and cervical HPV Papanicolaou smear of vagina with atypical squamous cells of undetermined significance (ASC-US) Papanicolaou smear of vagina with low grade squamous intraepithelial lesion (LGSIL) Vaginal high risk human papillomavirus (HPV) DNA test positive V01.6 Contact with or exposure to venereal diseases V23.9 Supervision of unspecified high-risk pregnancy V24.2 Routine postpartum follow-up V69.2 High-risk sexual behavior V70.0 Routine general medical examination at a health care facility V72.3 Gynecological examination V72.31 Routine gynecological examination Encounter for Papanicolaou cervical smear to confirm findings of V72.32 recent normal smear following initial abnormal smear V73.81 Special screening examination for Human papillomavirus (HPV) V76.2 Screening for malignant neoplasms of cervix V76.41 Screening for malignant neoplasms of rectum V76.47 Special screening for malignant neoplasms of vagina Proprietary Information of UnitedHealthcare. Copyright 2014 United HealthCare Services, Inc. Page 4

5 REFERENCES 1. American Cancer Society. Detailed Guide to Cervical Cancer. Atlanta: American Cancer Society; Available at: (Accessed: September 23, 2011). 2. Saslow D, Runowicz CD, Solomon D, Mosicki AB, Smith RA, Eyre HJ, Cohen C. American Cancer Society guideline for the early detection of cervical neoplasia and cancer. CA Cancer J Clin. 2002;52(6): Elfgren K, Kalantari M, Moberger B, Hagmar B, Dillner J. A population-based five-year follow-up study of cervical human papillomavirus infection. Am J Obstet Gynecol. 2000;183: Moscicki AB, Shiboski S, Broering J, et al. The natural history of human papillomavirus infection as measured by repeated DNA testing in adolescent and young women. J Pediatr. 1998;132: Ho GY, Bierman R, Beardsley L, et al. Natural history of cervicovaginal papillomavirus infection in young women. N Engl J Med. 1998;338: Schlecht NF, Kulag S, Robitaille J, et al. Persistent human papillomavirus infection as a predictor of cervical intraepithelial neoplasia. J Am Med Assoc. 2001;286: Bosch FX, Manos MM, Munoz N, et al. Prevalence of human papillomavirus in cervical cancer: a worldwide perspective. J Natl Cancer Inst. 1995;87: Walboomers JM, Jacobs MV, Manos MM, et al. Human papillomavirus is a necessary cause of invasive cervical cancer worldwide. J Pathol. 1999;189: 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. 2006;119: Arbyn M, Sasieni P, Meijer CJ, Clavel C, Koliopoulos G, Dillner J. Chapter 9: clinical applications of HPV testing: a summary of meta-analyses. Vaccine. 2006;24(suppl 3): S3/ Mayrand MH, Duarte-Franco E, Rodrigues I, et al. Human papillomavirus DNA versus Papanicolaou screening tests for cervical cancer. Canadian Cervical Cancer Screening Trial Study Group. N Engl J Med. 2007;357: Naucler P, Ryd W, Tornberg S, et al. Human papillomavirus and Papanicolaou tests to screen for cervical cancer [published erratum appears in N Engl J Med 2008;359:1637]. N Engl J Med. 2007;357: 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.2007;370: Castle PE, Fetterman B, Poitras N, Lorey T, Shaber R, Kinney W. Five-year experience of human papillomavirus DNA and Papanicolaou test cotesting. Obstet Gynecol. 2009;113(3): Ronco G, Giorgi-Rossi P, Carozzi F, et al. Results at recruitment from a randomized controlled trial comparing human papillomavirus testing alone with conventional cytology as the primary cervical cancer screening test. New Technologies for Cervical Cancer Screening Working Group. J Natl Cancer Inst. 2008;100: Proprietary Information of UnitedHealthcare. Copyright 2014 United HealthCare Services, Inc. Page 5

6 16. Dillner J, Rebolj M, Birembaut P, et al. Long term predictive values of cytology and human papillomavirus testing in cervical cancer screening: joint European cohort study. Joint European Cohort Study. BMJ. 2008;337:a Human papillomavirus. ACOG practice bulletin No.61. American College of Obstetricians and Gynecologists. Obstet Gynecol. 2005;105: Cervical Cytology Screening. ACOG practice bulletin No.109. American College of Obstetricians and Gynecologists. Obstet Gynecol 2009;114: Screening for cervical cancer. ACOG practice bulletin No.131. American College of Obstetricians and Gynecologists. Obstet Gynecol. 2012;120: Castle PE, Sideri M, Jeronimo J, Solomon D, Schiffman M. Risk assessment to guide the prevention of cervical cancer. Am J Obstet Gynecol Oct;197(4):356.e Wright TC, Massad LS, Dunton CJ, Spitzer M, Wilkinson EJ, Solomon D, for the 2006 American Society for Colposcopy and Cervical Pathology sponsored Consensus Conference consensus guidelines for the management of women with abnormal cervical cancer screening tests. Am J Obstet Gynecol. 2007;197: Manos MM, Kinney WK, Hurley LB, Sherman ME, Shieh-Ngai J, Kurman RJ, et al. Identifying women with cervical neoplasia: using human papillomavirus DNA testing for equivocal Papanicolaou results. JAMA. 1999; 281: Wright TC Jr, Lorincz A, Ferris DG, Richart RM, Ferenczy A, Mielzynska I, et al. Reflex human papillomavirus deoxyribonucleic acid testing in women with abnormal Papanicolaou smears. Am J Obstet Gynecol. 1998; 178: Shlay JC, Dunn T, Byers T, Baron AE, Douglas JM Jr. Prediction of cervical intraepithelial neoplasia grade 2-3 using risk assessment and human papillomavirus testing in women with atypia on papanicolaou smears. Obstet Gynecol. 2000;96: Bergeron C, Jeannel D, Poveda J, Cassonnet P, Orth G. Human papillomavirus testing in women with mild cytologic atypia. Obstet Gynecol. 2000;95: Results of a randomized trial on the management of cytology interpretations of atypical squamous cells of undetermined significance. ASCUS-LSIL Triage Study (ALTS) Group. Am J Obstet Gynecol. 2003;188: Katki HA, Kinney WK, Fetterman B, et al. Cervical cancer risk for women undergoing concurrent testing for human papillomavirus and cervical cytology: a population-based study in routine clinical practice. Lancet Oncol Jul;12(7): Wright TC Jr, Stoler MH, Sharma A, Zhang G, Behrens C, Wright TL; the ATHENA (Addressing THE Need for Advanced HPV Diagnostics) Study Group. Evaluation of HPV-16 and HPV-18 Genotyping for the Triage of Women With High-Risk HPV+ Cytology-Negative Results. Am J Clin Pathol Oct;136(4): Kjaer S, Hogdall E, Frederiksen K, et al. The absolute risk of cervical abnormalities in highrisk human papillomavirus-positive, cytologically normal women over a 10-year period. Cancer Res. 2006;66: Khan MJ, Castle PE, Lorincz AT, et al. The elevated 10-year risk of cervical precancer and cancer in women with human papillomavirus (HPV) type 16 or 18 and the possible utility of type-specific HPV testing in clinical practice. J Natl Cancer Inst. 2005;97: Proprietary Information of UnitedHealthcare. Copyright 2014 United HealthCare Services, Inc. Page 6

7 POLICY HISTORY/REVISION HISTORY Policy Effective Date Action/Description Proprietary Information of UnitedHealthcare. Copyright 2014 United HealthCare Services, Inc. Page 7