HPV: Everything You Want to Know: Part 1. Natural History, Screening Guidelines, Pap and HPV Co-Testing, and Vaccines

Transcription

1 HPV: Everything You Want to Know: Part 1. Natural History, Screening Guidelines, Pap and HPV Co-Testing, and Vaccines Nancy R. Berman MSN, ANP-BC, NCMP, FAANP Adult Nurse Practitioner/Colposcopist Certified Menopause Practitioner (NAMS) Millennium Affiliated Physicians Division of Michigan Healthcare Professionals Farmington Hills, Michigan Clinical Instructor Department of Obstetrics and Gynecology Wayne State University School of Medicine Detroit, Michigan

2 Objectives At the end of this session, the attendee will: 1. Describe the role of persistent oncogenic HPV in the development of pre-cancer and cancer of the cervix 2. Describe the use of HPV testing as co-testing along with the Pap in cervical cancer screening in women 30 and older 3. Describe the use of HPV primary screening in women 25 and older 4. Describe 3 important messages that NP's will teach women regarding HPV infection

3 Disclosures Consultant and Speaker: Hologic

4 Global Perspective on Cervical Cancer 5 th most common cancer in humans 2 nd most common cancer in women Most common cancer in many developing countries Relatively early age of death (median of 57 yrs versus 72 yrs for all cancers)

5 Cumulative Progression of Disease Among Women with HPV Persistence Cumulative incidence of clinical progression Yr 2Yr 3Yr 4Yr 5Yr 6Yr Nobbenhuis MAE et al Lancet 1999;354:20-25

6 Goal of Cervical Cancer Screening Prevent morbidity and mortality from cervical cancer by: Identifying and treating high-grade cervical cancer precursors Avoiding unnecessary and potentially hazardous evaluations and treatment Minimizing costs to healthcare system Increase benefit and decrease harm! Saslow D, et al. CA Cancer J Clin

7 Being rarely or never screened is the major contributing factor to most cervical cancer deaths today.

8 Who are the Rarely and Never Screened? Descriptions Minorities Low SES* Foreign born Living in the US < 10 years No usual source of health care Where are the data? US Census NCHS Cervical cancer mortality BRFSS µ NHIS** * Socio-economic status National Center for Health Statistics, CDC µ Behavioral Risk Factor Surveillance System, CDC ** National Health Interview Survey, CDC

9 What s to Know, What s New and What s Changed HPV Natural History

10 HPV and Cervical Cancer Virtually all cervical cancers are associated with persistent infection with high-risk HPV types Data from a variety of studies have confirmed that certain HPV types are associated with cervical cancer: 16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59 Others are probably associated, including: 26, 53, 66, 68, 73, 82 IARC. Monographs on the Evaluation of Carcinogenic Risks to Humans.; Munoz N. Vaccine

11 HPV Impact: Cervical Cancer In the US (2014 estimate): 12,340 cases per year 4,030 deaths per year Worldwide (2008 estimate): 530,000 cases per year 275,000 deaths per year 85% of deaths occur in developing countries Cervical cancer screening: costs $3.4 billion annually American Cancer Society. Cancer Facts and Figures. 2012; GLOBOCAN 2008 (IARC). Insinga RP. AJOG

12 Human Papillomavirus (HPV) Nonenveloped double-stranded DNA virus 1 1. Howley PM. In: Fields BN, Knipe DM, Howley PM, eds. Fields Virology. 4 th ed. Philadelphia, Pa: Lippincott-Raven; 2001: Reprinted with the permission of Lippincott-Raven. 2. Schiffman M, Castle PE. Arch Pathol Lab Med. 2003;127: Wiley DJ, Douglas J, Beutner K, et al. Clin Infect Dis. 2002;35(suppl 2):S210 S Muñoz N, Bosch FX, de Sanjosé S, et al. N Engl J Med. 2003;348: Clifford GM, Smith JS, Aguado T, Franceschi S. Br J Cancer. 2003:89; >100 types identified anogenital 2, oncogenic* types, 2,3 including 16, 18, 31, 33, 35, 39, 45, 51, 52, 58 4 HPV 16 (54%) and HPV 18 (13%) account for the majority of worldwide cervical cancers. 5 Nononcogenic types include: 6, 11, 40, 42, 43, 44, 54 4 HPV 6 and 11 are most often associated with external anogenital warts. 3

13 HPV and Cervical Cancer Virtually all cervical cancers are associated with persistent infection with high-risk HPV types Data from a variety of studies have confirmed that certain HPV types are associated with cervical cancer: 16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59 Others are probably associated: 26,53, 66, 68,73, 82 Oncogenic HPV is a necessary cause of cervical cancer! IARC. Monographs on the Evaluation of Carcinogenic Risks to Humans. (in press); Munoz N. Vaccine

14 HPV Types Associated with Cervical Cancer Clifford GM. Br Med J Africa Asia Europe North America

15 HPV Associated with Cancer and External Genital Warts Selected types Associated abnormalities = 0.5 High-Risk Types 16,18,31,33,35,39, 45,51,52,56,58,59, 68,82 Low-grade cervical lesions High-grade cervical lesions Low-Risk Types 6,11,40,42,43, 44,54,61,72,81 Low-grade cervical lesions External genital warts Anogenital cancers Soper D. Inf Dis Obstet Gynecol. 2006; Munoz N. N Engl J Med. 2003; Munoz N. Vaccine. 2006; Wallboomers JM. J Pathol.1999; De Villiers EM. Int J Cancer. 2004; zur Hausen H. J Nat Cancer Inst

16 HPV and Non-Cervical Cancers HPV 16 Evidence of causal role in cancer of vagina, vulva, penis, anus, oral cavity, oropharynx; limited evidence for carcinogenicity in the larynx HPV 18 Limited evidence of carcinogenicity in vagina, vulva, penis, anus, oral cavity, larynx HPV 6 and 11 Limited evidence of carcinogenicity in vulva, penis, anus, larynx Munoz N. Vaccine IARC. Monographs on the Evaluation of Carcinogenic Risks to Humans

17 High Lifetime Risk of HPV Infection 6.2 million new infections Approximately 20 million people in US currently are infected with HPV By age 50, 80% of sexually active women will have acquired genital HPV infection Weinstock H. Perspect Sex Reprod Health. 2004; CDC. Self-Study STD Module HPV Infection.

18 HPV Cumulative Incidence: Ho Study Three-year study of 608 college students Cumulative 36-month incidence of high-risk HPV in women negative at baseline: 43% By 12 months after infection,70% had cleared the infection By 24 months, over 90% had cleared the infection Most HPV infection will go away in a short period of time. Ho GYF. N Engl J Med

19 HPV Transmission Virus primarily transmitted via genital contact Primarily through sexual intercourse, including receptive anal intercourse Can also be transmitted by: Non-penetrating sexual activities Oral-genital contact Burchell AN. Vaccine

20 Risk Factors for Persistent HPV Infection and/or Neoplastic Progression Smoking HPV type Increasing age Lack of condom use Immunodeficiency (eg, HIV) Possibly OC use Possibly other STIs, such as chlamydia Moscicki A-B. Vaccine. 2006; Moscicki A-B. J Infect Dis. 2004; Hogewoning CJ. Int J Cancer

21 Role of Persistent Infection Persistent infection with high-risk types of HPV is necessary for the progression of high-grade lesions to invasive cancer Trottier H. Vaccine more

22 Role of Persistent Infection (Continued) Average episode lasts 4-20 months <50% of women have same type 1 year later Type 16 has a greater risk of persistence The longer oncogenic HPV infection persists, the greater the risk of neoplasia and progression to invasive cancer! Trottier H. Vaccine

23 Risk Factors for Persistent HPV Infection and/or Neoplastic Progression Smoking HPV type Increasing age Lack of condom use Immunodeficiency (eg, HIV) Possibly OC use Possibly other STIs, such as chlamydia Moscicki A-B. Vaccine. 2006; Moscicki A-B. J Infect Dis. 2004; Hogewoning CJ. Int J Cancer

24 HPV and Cervical Cancer Putting Risk Into Perspective Risk (odds) of cervical cancer with HPV 16 compared with HPV ( ) is 455. Risk of lung cancer in U.S. white male smoker compared with nonsmoker is only 8. Risk of breast cancer with hormone replacement therapy is only 1.8. Educate the Educator: ASCCP 2016

25 Natural History of HPV & Cervical Cancer Persistence Normal Cervix Infection Progression Invasion Clearance HPV Infection Regression Pre-cancer Cancer Courtesy of M. Schiffman, National Cancer Institute.

26 HPV Malignant Transformation Extrachromosomal HPV DNA Integrated HPV genes Host chromosome Deregulated expression of HPV E6 and E7 Interactions with cellular regulatory proteins Benign growth or wart Malignant tumour Beutner, Am J Med, 1997

27 Why Is the Cervix At Risk Understanding Transformation Zones

28 Transformation Zones and HPV Infection Area where one type of epithelium contacts and gradually replaces another through process of metaplasia Present in cervix, anus, tonsils Areas of HPV-related carcinogenesis Moscicki AB. Vaccine

29 Cervical Transformation Zone Source:

30 Cervical Cancer Is preventable Does not develop in the absence of high risk HPV Is usually asymptomatic May cause bleeding with intercourse, discharge or odor ANY CERVIX WITH AN APPEARANCE THAT IS GROSSLY ABNORMAL SHOULD PROMPT REFERRAL!

31 Warning Signs of Early Cervical Cancer Mimics of cervical cancer Severe cervicitis e.g. herpes, syphilis Benign ulceration e.g. trauma Foreign body reaction Granulomatous cervical conditions Granulom/inguinale Lymphogranloma venereum Schistosomiasis Cervical condylomata Colposcopy aids differentiation. Histology is the final arbiter

32 HPV Prevention

33 Prevention of HPV-Related Disease Primary prevention Preventing HPV infection Secondary prevention Identifying and treating high-grade precancerous lesions Tertiary prevention Treatment of cervical and other anogenital cancers.

34 HPV Primary Prevention

35 Risk Factors for HPV Infection Sexual Activity Multiple Partners Younger age at sexual debut Lack of condom use Ley C. J Natl Cancer Inst. 1991; Winer RL. N Engl J Med. 2006; Ho GYF. N Engl J Med

36 Condom Use and HPV Prevention Rate of HPV infection per 100 patient-years at risk Winer RL. N Engl J Med

37 HPV Vaccines

38 HPV Vaccination Before HPV exposure Boys and girls age 11 to 12 Catchup vaccination to age 26 Garland SM. N Engl J Med. 2007; Winer RL. J Infect Dis. 2005; CDC 2013; CDC 2014.

39 Previous and Current HPV Vaccines Licensed in U.S. *Bivalent and Quadrivalent no longer available in US: as of late 2016 Bivalent 2vHPV* (Cervarix) Quadrivalent 4vHPV (Gardasil) 9-Valent 9vHPV (Gardasil 9) Manufacturer GlaxoSmithKline Merck Merck HPV Types Included 16, 18 6, 11, 16, 18 6, 11, 16, 18, 31, 33, 45, 52, 58 Contraindications Hypersensitivity to latex* Hypersensitivity to yeast Hypersensitivity to yeast Dose Schedule 3 dose series: 0, 1, 6 months 3 dose series: 0, 2, 6 months 3 dose series: 0, 2, 6 months You Are the Key to HPV Cancer Prevention, CDC

40 HPV Vaccine Comparison These Genital warts ~66% of ~15% of HPV Types Cervical Cervical Cause: Cancers Cancers

41 Advisory Committee on Immunization Practice (ACIP) Guidelines

42 Current Recommendations: Advisory Committee on Immunization Practice (ACIP) Updated Recommendations of the Advisory Committee on Immunization Practices Routine and catch-up age groups Can be started at age 9 Females through age 26 Males through age 21 who were not adequately vaccinated previous Males age 22 through 26 may be vaccinated Meites E, Kempe A, Markowitz LE. Use of a 2- Dose Schedule for Human Papillomavirus Vaccination Updated Recommendations of the Advisory Committee on Immunization Practice. MMWR Morb Mortal Wkly Rep 2016;65:

43 Current Recommendations: Advisory Committee on Immunization Practice (ACIP) Use of 2 Dose Schedule for HPV Vaccination For persons initiating vaccination before their 15 th birthday: 2 doses of HPV vaccine 2 nd dose should be administered 6-12 months after the first dose (0, 6-12 month) schedule Meites E, Kempe A, Markowitz LE. Use of a 2- Dose Schedule for Human Papillomavirus Vaccination Updated Recommendations of the Advisory Committee on Immunization Practice. MMWR Morb Mortal Wkly Rep 2016;65:

44 Current Recommendations: Advisory Committee on Immunization Practice (ACIP) Use of 2 Dose Schedule for HPV Vaccination For persons initiating vaccination after their 15 th birthday, the recommended immunization is 3 doses of HPV vaccine Second dose should be administered 1-2 months after the first dose, and the third dose should be administered 6 months after the first dose (0, 1-2, 6 month schedule) Meites E, Kempe A, Markowitz LE. Use of a 2- Dose Schedule for Human Papillomavirus Vaccination Updated Recommendations of the Advisory Committee on Immunization Practice. MMWR Morb Mortal Wkly Rep 2016;65:

45 Current Recommendations: Advisory Committee on Immunization Practice (ACIP) Persons vaccinated previously: Any HPV vaccine before 15 th birthday and received 2 doses at dosing schedule (0, 1-2, 6 months) are considered adequately vaccinated Person who initiated any HPV vaccine on or after 15 th birthday, and received 3 doses are considered adequately vaccinated 9vHPV may be used to continue or complete a series started with 4vHPV or 2vHPV For person adequately vaccinated with 2vHPV or 4vHPV, no recommendation regarding additional vaccination with 9vHPV Meites E, Kempe A, Markowitz LE. Use of a 2- Dose Schedule for Human Papillomavirus Vaccination Updated Recommendations of the Advisory Committee on Immunization Practice. MMWR Morb Mortal Wkly Rep 2016;65:

46 Current Recommendations: Advisory Committee on Immunization Practice (ACIP) Interrupted schedules If the vaccination is interrupted, the series does not need to be restarted The number of recommend doses is based on age at administration of the first dose Meites E, Kempe A, Markowitz LE. Use of a 2- Dose Schedule for Human Papillomavirus Vaccination Updated Recommendations of the Advisory Committee on Immunization Practice. MMWR Morb Mortal Wkly Rep 2016;65:

47 Current Recommendations: Advisory Committee on Immunization Practice (ACIP) Special populations: For children with a history of sexual abuse or assault Routine HPV vaccination beginning at age 9 years For men who have sex with men, routine vaccination through age 26 years For transgender persons, routine vaccination as for all adolescents and vaccination through age 26 for those not previously adequately vaccinated Immunocompromised: 3 doses (0, 1-2, 6) for female and males age 9 though 26 Meites E, Kempe A, Markowitz LE. Use of a 2- Dose Schedule for Human Papillomavirus Vaccination Updated Recommendations of the Advisory Committee on Immunization Practice. MMWR Morb Mortal Wkly Rep 2016;65:

48 HPV Vaccination is Routinely Recommended Routine immunization for 11- and 12-yearolds includes HPV vaccination. Clinicians should recommend HPV vaccine on the same day and in the same way as the other vaccines for preteens. MMWR, August 29, 2014, Vo1 63, #RR05 You Are the Key to HPV Cancer Prevention, CDC

49 #1 Reason That a Parent Doesn t Vaccinate Their Child My Healthcare provider didn t recommend it. I didn t know it was so important. Newitt V, HPV Vaccination, Advance for Nurse Practitioners, July/August, 2015

50 What s to Know, What s New and What s Changed Secondary Prevention Identifying and treating high-grade precancerous lesions

51 Current Approach to Cervical Cancer Prevention Requires four separate but linked components: HPV vaccination Screening Cytology with or without HPV testing Stand alone HPV testing: HPV Primary Screening Evaluation of screen-positive women using colposcopy and cervical biopsy Treatment of women with biopsy-confirmed highgrade cervical cancer precursors Wright T. Obst Gynecol Huh WK, Ault KA, Chelmow D, Davey D, Goulart FA, Garcia FA, Kinney WK, et al. Use of primary high-risk human papillomavirus testing for cervical cancer screening: interim clinical guidance. Obstet Gynecol 2015:125:

52 2012 ACS/ASCCP/ASCP Cervical Cancer Screening Guidelines Saslow, Solomon, Lawson, et al. JLGTD, March 14, 2012 (online) Saslow, Solomon, Lawson, et al. CA: A Cancer J for Clinicians, March 14, 2012 (online)

53 Factors Indicating Need for More Frequent Screening HIV infection Immunosuppression DES exposure in utero Previous treatment for CIN 2, CIN 3, or cancer ACOG Practice Bulletin #

54 Age to Start Cervical Cancer Screening Factors to consider HPV infections are common in young women Cervical cancer is rare in adolescents/young women Evaluation of minor cytological abnormalities: Is expensive Causes anxiety Can lead to unnecessary treatments ACOG Committee on Gynecologic Practice. Obstet Gynecol

55 Guidelines: Age to Start Cervical Cancer Screening ACS/ASCCP/ASCP, ACOG, USPSTF agree: Start at age 21 regardless of age of sexual debut Moscicki AB, Cox JT. J Low Genit Tract Dis Saslow D. et al. CA Cancer J Clin. 2012; ACOG Committee on Practice Bulletins. Obstet Gynecol. 2012; USPSTF. Moyer VA on behalf of the USPSTF. Ann Intern Med

56 Cervical Cancer Incidence by Age Group, USCS*, Age Rate per 100, All ages 9.4 *United States Cancer Statistics includes data from CDC s National Program of Cancer Registries and NCI s Surveillance, Epidemiology and End Results Program.Saraiya M et al. Obstet Gynecol 2007;109:

57 Guidelines: Cervical Cancer Screening Interval ACS/ASCCP/ASCP and ACOG Pap testing every 3 years for women ages Preferred for women 30 and older: Cotesting with Pap and HPV test every 5 years Acceptable for women 30 and older: Pap testing alone every 3 years Saslow D. et al. CA Cancer J Clin ACOG. Obstet Gynecol more

58 Guidelines: Cervical Cancer Screening Interval (Continued) USPSTF Pap testing every 3 years for women ages For women ages 30-65, may have Pap test plus HPV test every 5 years to extend screening interval Moyer VA on behalf of the USPSTF. Ann Intern Med

59 Guidelines: Age to Stop Cervical Cancer Screening ACS, ASCCP, ASCP, and ACOG Can stop screening in women older than age 65 with no history of CIN2 within the past 20 years and with evidence of adequate negative screening* USPSTF Can stop at age 65 if adequate recent screening with normal Pap tests and are not at high risk for cervical cancer * defined as 3 consecutive normal Pap tests or 2 consecutive negative cotests within preceding 10 years, with the most recent test occurring within the past 5 years. Saslow D. et al. CA Cancer J Clin. 2012; ACOG Committee on Practice Bulletins. Obstet Gynecol ; USPSTF. Moyer VA on behalf of the USPSTF. Ann Intern Med. 2012

60 Guidelines: Screening Post- Hysterectomy ACS/ASCCP/ASCP, ACOG, USPSTF Guidelines Recommend against routine screening if hysterectomy performed for benign disease and no history of high-grade pre-cancer or greater Saslow D. CA Cancer J Clin. 2012; ACOG Committee on Practice Bulletins. Obstet Gynecol. 2012; Moyer VA on behalf of USPSTF. Ann Intern Med

61 Role of All Professionals. Advocate for evidenced based guidelines!

62 Avoid OVERPAPULATION Follow Guidelines! Neil Lonky ASCCP Biennial Meeting 2008

63 Interval Extension and Well Woman Visit Pap is only one part of the annual well woman exam Unteach women about annual cervical screening Individualized: age, prior screening, HPV status Pap only part of visit, and not every year The annual exam should include Screening, evaluation, counseling, immunizations per age, risk factors Cervical Cytology Screening. ACOG Practice Bulletin No American College of Obstetricians and Gynecologists. Obstet Gynecol 2009; 114:

64 July 1, 2014

65 June 30, 2014

66 HPV Testing

67 Why Test for HPV? Persistent high risk HPV is necessary for the development of cervical cancer An obvious corollary is that the absence of HPV means that the risk of cervical cancer is negligible The negative predictive value for combined HPV Testing and the Pap has been shown to be 99.21% for CIN3. Sherman ME, et al. J Nat Cancer Inst. 2003;95:46-52.

68 HPV Testing for Screening: Stratifies Risk Allows for less frequent testing Identifies women who need increased surveillance Wright TC. Obstet Gynecol Katki HA et al. Lancet Oncol

69 ACS/ASCCP/ASCP health care providers can rely on the negative predictive value of the HPV test to assure women who cotest negative that they are at very low risk for CIN3 and cancer for at least 5 years after negative cotesting. Saslow D, et al. Ca J Clin

70 HPV Detection with FDA-Approved Tests Four tests are currently FDA approved and commercially available in the US One is approved for primary, stand-alone screening more

71 HPV Tests Available Tests HPV Types Detected Identifies HPV Type Hybrid Capture 2 High and low risk panels (request high risk only) Cervista HPV HR High risk No (add on test for 16 and 18) cobas HPV Test High risk Yes for 16 and 18 No APTIMA HPV mrna assay High risk No (add on test for 16, 18, and 45) ASCCP. Educate the Educators: HPV and the HPV Vaccines

72 Pap Classification System The Bethesda System

73 Pap Test Classification System Squamous cell abnormalities Atypical squamous cells of undetermined significance (ASC-US) Atypical squamous cells cannot exclude HSIL (ASC-H) Low-grade squamous intraepithelial lesion (LSIL) High-grade intraepithelial lesion (HSIL) Squamous cell carcinoma Solomon D. JAMA

74 Pap Test Classification System, cont d Glandular cell abnormalities Atypical glandular cells (AGC) endocervical origin, endometrial origin or NOS (not otherwise specified) Atypical glandular cells, favor neoplastic Adenocarcinoma in situ (AIS) Adenocarcinoma Solomon D. JAMA

75 Clinical Significance of ASC-US Most common cytology abnormality (mean rate in US 2003 was 4.7%) 2.5 million cases per year in US Prevalence of CIN 2/3 among women with ASC-US is 7-12% in the US Almost half of all CIN 2/3 cases are diagnosed in women with ASC-US Davey DD. Arch Pathol Lab Med. 2004; Wright T. AJOG in press; Solomon D. JAMA

76 Clinical Significance of ASC-H Uncommon cytology abnormality (mean rate in 2003 was 0.43%) Much higher risk of CIN 2/3 in women with ASC-H than those with ASC-US (40% vs 15%) Prevalence of CIN 2/3 among women with ASC-H ranges from 26% to 68% Wright T. AJOG in press; Davey DD. Arch Pathol Lab Med. 2004; Solomon D. JAMA

77 Clinical Significance of LSIL Common cytology abnormality Found more commonly in liquid-based cytology specimens (mean rate in 2003 was 2.6%) Good indicator of HPV infection Pooled estimate showed that 77% of women with LSIL are positive for high-risk HPV Prevalence of CIN 2/3 among women with LSIL ranges from 12% to 16% Wright T. AJOG in press; Davey DD. Arch Pathol Lab Med. 2004; Arbyn M. Vaccine. 2006; Solomon D. JAMA

78 Clinical Significance of HSIL Relatively uncommon cytology abnormality (mean rate in 2003 was 0.7%) Rate varies with age 0.6% in women yrs old versus 0.2% in women yrs old Prevalence of CIN 2/3 53% to 66% in women evaluated with colposcopy/biopsy 84% to 97% in women evaluated using a loop excision Approximately 2% of women with HSIL have invasive cancer Wright T. AJOG in press; Davey DD. Arch Pathol Lab Med. 2004; Solomon D. JAMA

79 Clinical Significance of AGC Relatively uncommon cytology abnormality (0.4% in 2003) AGC is more common in women 40 yrs and older Recent series have reported that 3-17% have invasive cancer - including adenocarcinomas of the cervix, endometrium, ovary, and fallopian tube Wright TC, Jr. AJOG. 2007; Davey DD. Arch Pathol Lab Med. 2004; Solomon D. JAMA

80 Co-testing Pap and HPV testing

81 Screening For Women Ages Preferred: Cytology + HPV testing (Cotesting) every 5 years Acceptable: Cytology alone every 3 years

82 Rationale for Cotesting Ages Increased detection of prevalent CIN3 Decreased CIN3 in subsequent screening rounds Achieves risk of CIN3 equal to cytology 1-3 year intervals Enhances detection of adenocarcinoma/ais Minimizes the increased number of colposcopies, thus it reduces harms.

83 Why Not Annual Cotesting? High negative predictive value of one cotest means most abnormal screens at 1-3 year intervals are transient HPV infection, not precancer Potential harms are amplified without benefit

84 Screening Interval for Combined Pap and HPV Testing in Women 30 and Older: Co-Testing HPV Result Cytology Recommended Management Negative Negative Cotest in 5 years Negative ASC-US Cotest in 3 years Positive ASC-US Colposcopy Negative LSIL Repeat cotesting in 1 year preferred; colposcopy acceptable Positive Pap > LSIL Colposcopy Any Positive HSIL Negative Colposcopy or immediate loop electrosurgical excision Option 1: Cotest in 12 months Option 2: Reflex to genotyping for HPV 16/18. If positive, colposcopy. If negative, cotest in 12 months Massad LS, et al. J Low Genit Tract Dis Saslow D. CA Cancer J Clin 2012.

85 Genotyping to Triage Women 30 with Pap-/HPV+ Results Genotyping Positive for 16 or 18 Negative for 16 and 18 Immediate colposcopy Co-testing in 12 months

86 Management of Repeat Testing After HPV +, Cytology - Results HPV Result Cytology Recommended Management Negative Negative Repeat cotesting in 3 years Positive Negative Perform colposcopy Any Pap > ASC-US Perform colposcopy Massad LS, et al. J Low Genit Tract Dis Saslow D. CA Cancer J Clin 2012.

87 High-risk HPV testing in the US Use of test % HR HPV testing Ever used 70 Not as recommended 54 At patient's request 60 ASC-US 81 ASC-H 77 LSIL 62 HSIL 60 Adjunct to cytology Ever used Women <30 Women Data from National breast and cervical cancer early detection program HR HPV testing has been used by 70% of providers but not always as advised in the ASCCP guidelines Saraiya M, et al. Cancer 2007; 110: