HUMAN PAPILLOMAVIRUS TESTING

Transcription

1 CLINICAL GUIDELINES For use with the UnitedHealthcare Laboratory Benefit Management Program, administered by BeaconLBS HUMAN PAPILLOMAVIRUS TESTING Policy Number: PDS Effective Date: October 1, 2018 Table of Contents Page GUIDELINES 1 BACKGROUND 2 CLINICAL EVIDENCE 2 GUIDELINES AND RECOMMENDATIONS 4 US FOOD AND DRUG ADMINISTRATION (US FDA) 5 CENTERS FOR MEDICARE AND MEDICAID SERVICES (CMS) 5 APPLICABLE CODING 5 REFERENCES 6 POLICY HISTORY/REVISION HISTORY 9 INSTRUCTIONS FOR USE Physician Decision Support (PDS) is a lab ordering tool operated by BeaconLBS. This Clinical Guideline supports the Questions and Answers that appear in PDS for tests referenced in this document. UnitedHealthcare reserves the right, in its sole discretion, to modify its Clinical Guidelines as necessary. This Clinical Guideline is provided for informational purposes. It does not constitute a Medical Policy or medical advice GUIDELINES BeaconLBS recommends Human Papillomavirus (HPV) testing for the following screening and management purposes: Screening Recommendations: HPV testing may be used as co-testing with cytology in women between the ages of 30 to 64. A negative HPV test with normal cytology results may allow for a decreased frequency of surveillance. Management Recommendations: HPV testing in women > 21 years of age can be used to stratify risk in conjunction with a cytology result of ASCUS. It may also be used in women > 65 years of age in conjunction with a cytology result of LSIL. BeaconLBS does not recommend that Human Papillomavirus (HPV) testing be undertaken in women < 21 years of age. Proprietary Information of UnitedHealthcare. Copyright 2018 United HealthCare Services, Inc. Page 1

2 These recommendations are consistent with current evidence-based guidelines from the American Society for Colposcopy and Cervical Pathology(ASCCP), American Cancer Society (ACS), American Society of Clinical Pathology (ASCP), and U.S. Preventive Services Task Force (USPSTF), and are supported by the American College of Obstetrics and Gynecologists (ACOG). BACKGROUND *Note: For additional background on cervical cancer and the Gynecologic Pap Test see Clinical Policy number PDS 015. 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 HPV, a sexually transmitted infection, has been strongly linked to cervical cancer. It has been stated that the demonstration that cervical cancer is caused by the persistent infection by certain genotypes of HPV is one of the most important discoveries in the investigation of cancer etiology over the past 25 years. 2 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. 3-6 Sometimes, however, in a small fraction of women the infection persists and becomes chronic. 4 It is this small group of women, chronic carriers of certain HPV genotypes, who have a high risk of disease progression and development of neoplastic lesions of the anogenital tract. 2, 7 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 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 1, 3, 8, 9 contain DNA from high risk types of HPV and HPV 16 and 18 are implicated in two-thirds of all cervical cancers. HPV DNA testing 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. The Food and Drug Administration (FDA) approved the first test for HPV in Since then, there are multiple tests available for use with cervical samples. These HPV tests are molecular based and detect HPV DNA or RNA. CLINICAL EVIDENCE Proprietary Information of UnitedHealthcare. Copyright 2018 United HealthCare Services, Inc. Page 2

3 Even though the Pap test has saved countless lives, it is not a perfect test. The Pap test sensitivity for the detection of high-grade CIN is in the range of 70-80%. 2 This has led to the development of additional tests aimed at increasing the sensitivity for detection of high grade cervical disease. 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 Another feature of HPV tests is the possibility to increase the time between screenings. The combination of cytology and high risk HPV testing may significantly improve the rate of detection of cervical cancer precursors and facilitate the safe lengthening of the screening interval. 21 HPV Testing Until recently in the US, the use of HPV testing as a primary screening method for cervical cancer was not approved by the FDA. 1-3 In April 2014, the FDA approved the first HPV DNA test for women 25 and older that can be used alone as primary screening for cervical cancer. 22 The test can be used to determine if women need to undergo additional diagnostic testing for cervical cancer or can be used to determine the woman's risk for future development of cervical cancer. The cobas HPV Test detects DNA from 14 high-risk HPV types (including HPV 16 and 18) using a sample of cervical cells. The FDA states in the press release that "Health care professionals should use the cobas HPV Test results together with other information, such as the patient screening history and risk factors, and current professional guidelines." 21 A task force appointed by the Society of Gynecologic Oncology (SGO) and the American Society of Colposcopy and Cervical Pathology (ASCCP) have prepared an interim clinical guidance document for HPV primary screening in the United States. 23 Currently, there is interest in using the HPV test as a triage test to stratify risk of women age 21 and older with ASC-US cytology and post-menopausal women with LSIL cytology. 18, 19 Additionally, concurrent testing for HPV 18, 19 and cervical cytology (co-testing) is an approved alternative to cytology alone in women 30+ years. Using HPV Testing for Triage of Abnormal Cytology Results HPV DNA testing in women over the age of 21 is an effective way to triage ASCUS cytology. 11, 21, HPV DNA testing should not be used for women under the age of 21 due to the high proportion of women with transient 18, 19 HPV infections and a positive result may lead to potentially harmful and costly overtreatment. Arbyn et al completed a 20 study meta-analysis to determine the efficacy of HPV DNA testing for use in ASCUS triage. 11 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%. Proprietary Information of UnitedHealthcare. Copyright 2018 United HealthCare Services, Inc. Page 3

4 Performing HPV DNA testing as a reflex for high grade squamous intraepithelial lesion (HSIL) has little clinical utility as more than likely the results will be positive. 18, 19 Additionally, HPV DNA results are often positive in women with LSIL, thereby making the use of HPV DNA testing as a triage for LSIL cytology difficult. 11 An exception 21, 29 to this is in post-menopausal women with LSIL cytology results where HPV DNA testing is recommended. Co-testing: Cervical Cytology and HPV Testing Concurrent testing for HPV and cervical cytology (co-testing) is an acceptable alternative to cytology alone in women 30+ years. 21, 30 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. 31 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. 10 For comparison, pooled sensitivity and specificity of cytology at a threshold of ASCUS are 60% and 97%, respectively. Sensitivity using a 10, 18 combination of HPV and cytology is significantly higher than that of either test alone with NPVs of %. 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. 32 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. 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. 11, 17-19, 28 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. 34 Guidelines and Recommendations American Society for Colposcopy and Cervical Pathology (ASCCP), American Cancer Society (ACS), American Society of Clinical Pathology (ASCP) 19 These following are current 2012 and 2013 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 (see Figure ) 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 (see Proprietary Information of UnitedHealthcare. Copyright 2018 United HealthCare Services, Inc. Page 4

5 Figure * In 2017, the USPSTF drafted new recommendation to exclude co-testing as a screening option for women aged Management For women aged 25 and above with ASC-US cytology, reflex HPV testing is preferred (see Figure ) For women aged years with ASC-US, reflex HPV testing is acceptable (see Figure ) Acceptable options for the management of postmenopausal women with LSIL and no HPV test include obtaining HPV testing US FOOD AND DRUG ADMINISTRATION (US FDA) The US FDA is involved in multiple aspects of the gynecologic Pap test including approval of new screening methods. CENTERS FOR MEDICARE AND MEDICAID SERVICES (CMS) For Medicare populations, CMS does not pay for screening procedures (tests) performed in the absence of signs or symptoms. (Section 1862(a)(7) of the Social Security Act) Medicare does not have a National Coverage Determination (NCD) for Human Papillomavirus (HPV) Testing. CPTs 87623, 87624, are addressed in the Local Coverage Determination (LCD) for Human Papillomavirus (HPV) Testing and compliance with these policies is required where applicable. (Accessed December 30, 2013) APPLICABLE CODING CPT Code Description Infectious agent detection by nucleic acid (DNA or RNA); human papillomavirus (HPV), low-risk types (eg, 6, 11, 42, 43, 44) Infectious agent detection by nucleic acid (DNA or RNA); human papillomavirus (HPV), high-risk types (eg, 16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 68) Infectious agent detection by nucleic acid (DNA or RNA); human papillomavirus (HPV), types 16 and 18 only, includes type 45, if performed Proprietary Information of UnitedHealthcare. Copyright 2018 United HealthCare Services, Inc. Page 5

6 REFERENCES 1. Lavanchy D. The global burden of hepatitis C. Liver international : official journal of the International Association for the Study of the Liver. 2009;29 Suppl 1: Castellsague X. Natural history and epidemiology of HPV infection and cervical cancer. Gyn Oncol. 2008:S4-S7. 3. Saslow D,Runowicz CD, et al. American Cancer Society guideline for the early detection of cervical neoplasia and cancer. CA: a cancer journal for clinicians. 2002;52(6): Elfgren K,Kalantari M, et al. A population-based five-year follow-up study of cervical human papillomavirus infection. American journal of obstetrics and gynecology. 2000;183(3): Moscicki AB,Shiboski S, et al. The natural history of human papillomavirus infection as measured by repeated DNA testing in adolescent and young women. The Journal of pediatrics. 1998;132(2): Ho GY,Bierman R, et al. Natural history of cervicovaginal papillomavirus infection in young women. The New England journal of medicine. 1998;338(7): Schlecht NF,Kulaga S, et al. Persistent human papillomavirus infection as a predictor of cervical intraepithelial neoplasia. JAMA. 2001;286(24): Bosch FX,Manos MM, et al. Prevalence of human papillomavirus in cervical cancer: a worldwide perspective. International biological study on cervical cancer (IBSCC) Study Group. Journal of the National Cancer Institute. 1995;87(11): Walboomers JM,Jacobs MV, et al. Human papillomavirus is a necessary cause of invasive cervical cancer worldwide. The Journal of pathology. 1999;189(1): Cuzick J,Clavel C, et al. Overview of the European and North American studies on HPV testing in primary cervical cancer screening. International journal of cancer. Journal international du cancer. 2006;119(5): Arbyn M,Sasieni P, et al., Chapter clinical applications of HPV testing: a summary of meta-analyses, in Vaccine 24suppl 3 S p Mayrand M-H,Duarte-Franco E, et al. Human papillomavirus DNA versus Papanicolaou screening tests for cervical cancer. The New England journal of medicine. 2007;357(16): 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 NWJ,Berkhof J, 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(9601): Castle PE,Fetterman B, et al. Five-year experience of human papillomavirus DNA and Papanicolaou test cotesting. Obstetrics and gynecology. 2009;113(3): Ronco G,Giorgi-Rossi P, 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. Journal of the National Cancer Institute. 2008;100(7): Proprietary Information of UnitedHealthcare. Copyright 2018 United HealthCare Services, Inc. Page 6

7 17. Dillner J,Rebolj M, et al. Long term predictive values of cytology and human papillomavirus testing in cervical cancer screening: joint European cohort study. BMJ (Clinical research ed.). 2008;337:a American College of OAG. ACOG Practice Bulletin. Clinical Management Guidelines for Obstetrician- Gynecologists. Number 61, April Human papillomavirus. Obstetrics and gynecology. 2005;105(4): American College of Obstetrics and Gynecologists. ACOG Practice Bulletin No. 157 Summary: Cervical Cancer Screening and Prevention. Obstet Gynecol. 2016;127(1): Castle PE,Sideri M, et al. Risk assessment to guide the prevention of cervical cancer. American journal of obstetrics and gynecology. 2007;197(4):356.e Wright TC,Massad LS, et al consensus guidelines for the management of women with abnormal cervical cancer screening tests. American journal of obstetrics and gynecology. 2007;197(4): Alter MJ. Epidemiology of hepatitis C virus infection. World Journal of Gastroenterology. 2007;13(17): Huh WK,Ault KA, et al. Use of primary high-risk human papillomavirus testing for cervical cancer screening: Interim clinical guidance. Gynecologic Oncology. 2015;136(2): Manos MM,Kinney WK, et al. Identifying women with cervical neoplasia: using human papillomavirus DNA testing for equivocal Papanicolaou results. JAMA. 1999;281(17): C. T,Lorincz A, et al. Wright Reflex human papillomavirus deoxyribonucleic acid testing in women with abnormal Papanicolaou smears. Am Gynecol. 1998: Shlay JC,Dunn T, et al. Prediction of cervical intraepithelial neoplasia grade 2-3 using risk assessment and human papillomavirus testing in women with atypia on papanicolaou smears. Obstetrics and gynecology. 2000;96(3): Bergeron C,Jeannel D, et al. Human papillomavirus testing in women with mild cytologic atypia. Obstetrics and gynecology. 2000;95(6 Pt 1): Aspinall R and Pockros P. The management of side effects during therapy for hepatitis C. Alimentary pharmacology & therapeutics. 2004;20(9): Mangia A,Santoro R, et al. Peginterferon alfa-2b and ribavirin for 12 vs. 24 weeks in HCV genotype 2 or 3. New England Journal of Medicine. 2005;352(25): HRSA, Health Resources & Services Administration. Women s Preventive Services 2016 Guidelines. Available at: Katki HA,Kinney WK, et al. Cervical cancer risk for women undergoing concurrent testing for human papillomavirus and cervical cytology: a population-based study in routine clinical practice. The Lancet. Oncology. 2011;12(7): Wright TC and Stoler MH. the ATHENA (Addressing for Advanced Study Group). Evaluation of HPV16 and HPV18 Genotyping for the Triage of Women With CytologyNegative Results Am Pathol Oct. 2011;136: Kjaer S,Høgdall E, et al. The absolute risk of cervical abnormalities in high-risk human papillomaviruspositive, cytologically normal women over a 10-year period. Cancer research. 2006;66(21): Proprietary Information of UnitedHealthcare. Copyright 2018 United HealthCare Services, Inc. Page 7

8 34. Khan MJ,Castle PE, 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. Journal of the National Cancer Institute. 2005;97(14): Le Guillou-Guillemette H and Lunel-Fabiani F, Detection and quantification of serum or plasma HCV RNA: mini review of commercially available assays. Methods Mol Biol,2009. p Proprietary Information of UnitedHealthcare. Copyright 2018 United HealthCare Services, Inc. Page 8

9 POLICY HISTORY/REVISION HISTORY Date Action/Description 11/08/2018 Annual Policy Review Completed changes made: Updated USPSTF 2017 recommendations under Screening paragraph and added USPSTF reference. 10/06/2016 Annual Policy Review Completed changes made: Clinical Evidence Section and HPV subsection: Modified the following statement to reflect that the clinical guidance has been published: "A task force appointed by the Society of Gynecologic Oncology (SGO) and the American Society of Colposcopy and Cervical Pathology (ASCCP) have prepared an interim clinical guidance document for HPV primary screening in the United States. References Section: Updated ACOG reference from practice bulletin No. 131 version 2012 to practice bulletin No. 157 version /03/2015 Annual Policy Review Completed changes made: Added reference: Huh, Added sentence in 'Recommendations' section, under 'Screening Recommendations': "Primary hrhpv screening may be undertaken.and Society for Gynecologist Oncologists (SGO)," based on the Huh, 2015 reference. Added paragraph in 'Clinical Evidence' section, under 'HPV Testing': "The SGO and the ASCCP...test that is positive for HPV types other than 16 or 18 should be followed with cytology testing." based on the Huh, 2015 reference. 10/01/2015 Deleted CPT and added CPTs 87623,87624,87625 as per AMA 2015 updates 10/23/2014 Reference added in reference section: FDA News Release. FDA approves first human papillomavirus test for primary cervical cancer screening. Available at: (Accessed: October 10, 2014). Within the body of the policy, in the "Clinical Evidence" - "HPV Testing", the following was added: "Until recently in the US, the use of HPV testing as a primary screening method for cervical cancer was not approved by the FDA.1-3 In April 2014, the FDA approved the first HPV DNA test for women 25 and older that can be used alone as primary screening for cervical cancer.21 The test can be used to determine if women need to undergo additional diagnostic testing for cervical cancer or can be used to determine the woman's risk for future development of cervical cancer. The cobas HPV Test detects DNA from 14 high-risk HPV types (including HPV 16 and 18) using a sample of cervical cells. The FDA states in the press release that "Health care professionals should use the cobas HPV Test results together with other information, such as the patient screening history and risk factors, and current professional guidelines."21 A task force appointed by the Society of Gynecologic Oncology (SGO) and the American Society of Colposcopy and Cervical Pathology (ASCCP) are preparing an interim clinical guidance document for HPV primary screening in the United States which is expected to be published in the next few months." "Currently, there is interest in using the HPV test as a triage test to stratify risk of women age 21 and older with ASC-US cytology and post-menopausal women with LSIL cytology Additionally, concurrent testing for HPV and cervical cytology (co-testing) is an approved alternative to cytology alone in women 30+ years.18-19" Proprietary Information of UnitedHealthcare. Copyright 2018 United HealthCare Services, Inc. Page 9