HPV: Everything You Want to Know: Part 2. Primary (Stand alone) HPV Testing, Anal Cancer Screening and Counseling Tips

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1 HPV: Everything You Want to Know: Part 2. Primary (Stand alone) HPV Testing, Anal Cancer Screening and Counseling Tips 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 What s to Know, What s New and What s Changed Management of Abnormal Cervical Cancer Screening Results

3 Managing Abnormal Cervical Cancer Precursors Guidelines cannot be developed for all situations Clinical judgment should always be applied when applying guidelines to individual patients Massad LS, et al. J Low Genit Tract Dis

4 Potential Harms From Cervical Cancer Screening Anxiety from an abnormal test that the patient might fear to be a sign of cancer Stigma from diagnosis of a ubiquitous sexually transmitted infection (HPV) Time and patient expense related to screening and management Pain and injury from the procedures and treatment Increased risk of premature delivery and pregnancy loss Einstein, M, Cox, J.T., Cervical Disease, OBG Management, Vol.25, May 2013

5 Guidelines Are Meant to Increase Benefits and Decrease Harms! Complicated? HELP IS AVAILABLE!

6 2013 American Society for Colposcopy and Cervical Pathology (ASCCP) Guidelines Download Algorithms Mobile App: iphone and Android

7 What s to Know, What s New and What s Changed 2013 Algorithms: Essential to Know Introduction to guidelines for some of the most common cytologic abnormalities

8 2013 Algorithms: Essential to Know Cytology Cytology: negative, but lacking endocervical cells an be managed WITHOUT a repeat earlier than when the next cytology is due Cytology: Unsatisfactory requires repeat even if HPV if negative

9 2013 Algorithms: Essential to Know Reflex genotyping or immediate genotyping when available, is used in the triage of the Pap/negative, HPV/positive woman Genotype positive for HPV 16 or 18 leads to immediate colposcopy Genotype HPV 16/18 negative leads to repeat co-testing in 12 months

10 Management of Young Women Annual incidence of cervical cancer in US women ages 21 to 24 = 1.4/100,000 Almost 55,000 cytology tests run for every cervical cancer diagnosis in this age group Justifies need for screening, but suggests observation for minor abnormalities If an adolescent is screened inappropriately and has an abnormal Pap test, refer to guidelines for women ages 21 to 24. Benard VB, et al. Obstet Gynecol Massad LS, et al. J Low Genit Tract Dis

11 2013 Algorithms: Essential to Know 21 to 24 years old women have a separate algorithm for abnormal results Similar management for similar risk strategies ASC-US, LSIL: no longer go straight to colposcopy Pap follow-up in 12 months, even if there is a triage to HPV and it is positive!

12 2013 Algorithms: Essential to Know ASC-US Cytology Age 25 to 65 ASC-US/HPV negative: co-testing at 3 years (routine follow-up after Pap and HPV negative is 5 years)

13 Management of Postmenopausal/Aged 65 and older Women with ASC-US Postmenopausal women should be managed in the same manner as women in the general population For women 65 and older exiting from screening, HPV-negative/ASC-US results should be considered abnormal. Additional surveillance with cotesting in 12 months is recommended. Massad LS, et al. J Low Genit Tract Dis

14 Primary HPV Testing for Cervical Cancer Screening Stand-alone HPV test

15

16 FDA approves first human papillomavirus test for primary cervical cancer screening The U.S. Food and Drug Administration today approved the first FDA-approved HPV DNA test for women 25 and older that can be used alone to help a health care professional assess the need for a woman to undergo additional diagnostic testing for cervical cancer. The test also can provide information about the patient s risk for developing cervical cancer in the future.

17 2014 FDA Approval for Primary HPV Testing for Cervical Cancer Screening Rationale More sensitive and reproducible than cytology Assesses current and future risk More cost-effective for large-volume screening May be more useful in women vaccinated against HPV Educate the Educator: ASCCP 2016

18 Why HPV Primary Screening? Co-testing (Pap and HPV testing) is only marginally better than HPV testing alone!

19 FDA Approved Tests for Primary HPV Screening (Stand Alone Testing) cobas HPV Test Provides genotyping for HPV 16 and18 concurrently with testing for the presence of 12 other high-risk HPV types Onclarity Test Provides genotyping for HPV 16, 18, 45 and concurrently with testing for the presence of 11 other high risk types

20 Issues to Consider With Cytology Highly subjective test: substantial inter- and intralaboratory variability and limited reproducibility Misses quite a few cervical cancers Unable to identify those women who are at future risk of developing cervical cancer precursors Unclear how cytology will perform as HPV vaccine uptake rates increase in the US

21 Performance of Cervical Cytology Sensitivity for >CIN2 Author Year Number Method Sensitivity 95% CI Petry ,466 Conv 44% (30-58%) Coste ,080 Conv 65% (50-80%) Taylor ,114 LBC 71% (58-81%) Ronco ,760 LBC 74% (62-84%) Mayrand ,153 Conv 57% (34-78%) 2012 US Preventative Task Force Review

22 Variability of Cervical Cytology Cytology for the ATHENA study Educate the Educator: ASCCP 2016

23 Importance of Genotyping for HPV 16 &18 Over two thirds of cervical cancers in the United States are caused by HPV 16 &18 Other individual high-risk HPV genotypes are associated with far fewer cancers Persistent HPV 16 infection confers a very high risk for CIN 3+, as shown in multiple long-term studies Educate the Educators, ASCCP 2016

24 Predictive Value of HPV Genotyping National Cancer Institute-Kaiser Northwest Study 20,817 women with satisfactory cytology at enrollment ( ) Archived samples tested with PCR for HPV Follow-up with cytology, standard workup for abnormal findings Case-control design (women with/without CIN) Women followed for up to 15 y (median = 10.5 y) Educate the Educators, ASCCP 2016

25 Predictive Value of HPV Genotyping 15-y risk of CIN 3+ in Kaiser Northwest cohort Educate the Educator: ASCCP 2016

26 What Study Led to FDA Approval for Primary HPV Testing? ATHENA Addressing the Need for Advanced HPV Diagnostics

27 ATHENA: Addressing the Need for Advanced HPV Diagnostics Prospective, multicenter, US-based study of 47,208 women aged 21 and older Recruited at time of routine screening 2.6% had been vaccinated against HPV Screened by liquid based cytology and HPV test

28 ATHENA Designed to assess the medical utility of pooled high-risk HPV DNA in addition to genotyping for HPV 16 and 18 in 3 populations Women 21 and older with a cytologic finding of ASC-US Women 30 and older with normal cytology Women aged 25 and older in the overall screening population with any cytologic finding

29 Absolute Risk of CIN in Cytology- Women Women 30 years, Athena Study Wright TC, Stoler MH, Behrens CM, et al. Primary cervical cancer screening with human papillomavirus: End of study results from the ATHENA study using HPV as the first-line screening test. Gynecol Oncol. 2015;136(2): Educate the Educator ASCCP 2016

30 Proportion of CIN3 by Age Group Athena Trial: Why Start Primary Screening at Age 25 Wright TC, Stoler MH, Behrens CM, et al. Primary cervical cancer screening with human papillomavirus: End of study results from the ATHENA study using HPV as the first-line screening test. Gynecol Oncol. 2015;136(2): Educate the Educator ASCCP 2016

31 Primary High Risk Human Papillomavirus Testing for Cervical Cancer Screening Interim Clinical Guidance 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:

32 Interim Clinical Guidance Published Obstetrics & Gynecology, February 2015 Rationale: A negative hrhpv test provides grater reassurance of low CIN3+ risk than a negative cytology result Because of equivalent or superior effectiveness, primary hrhpv screening can be considered as an alternative to current U.S> cytology-based cervical cancer screening methods. Cytology alone and cotesting remain the screening options specifically recommended in major guidelines 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:

33 Interim Clinical Guidance Based on limited data: Triage of hrhpv positive women using a combination of genotyping for HPV 16 and 18 And reflex cytology for women positive for the 12 other hrhpv genotypes appears to be a reasonable approach to managing hrhpv-positive women 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:

34 Cumulative incidence rate of CIN3 (%) Women with HPV16 and HPV18 infections are more likely to develop high-grade disease HPV16+ HPV18+ Other high-risk HPV+ High-risk HPV % (11.5, 22.9) 13.6% (3.6, 23.7) Follow-up time (months) % (1.9, 4.2) 0.8% (0.6, 1.1) Khan MJ, et al. J Natl Cancer Inst 2005; 97:

35 Interim Clinical Guidance Rescreening after a negative primary hrhpv screen should occur NO SOONER than every 3 years 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:

36 Interim Clinical Guidance Primary hrhpv screening can be considered as an alternative to current U.S. cytology alone or cotesting HPV 16/18 genotyping and reflex cytology for women positive for the other 12 types: achieves a reasonable balance of disease detection with the number of screening tests and colposcopies required to achieve that detection 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:

37 The HPV primary screening algorithm cobas HPV Test other hrhpv+ HPV Cytology HPV16/18+ NILM ASC-US Routine screening Follow-up in 12 months Colposcopy

38 HPV Primary Screening New ACOG Guidelines Recommends following the SGO/ASCCP guidelines if HPV primary screening is used Additional recommendations: Stop screening women at 65 y who have a history of negative findings. Do not use HPV testing to screen women who have had a hysterectomy. Follow-up with cotesting at 12 months if HPV+ and cytology-negative and HPV 16/18 negative. Use only the FDA approved test. Educate the Educators: ASCCP 2016

39 NEW USPSTF RECOMMENDATIONS PUBLISHED 8/21/18 Women aged 21 to 29 years Cytology alone every 3 years Women aged 30 to 65 Cytology alone every 3 years High-risk HPV (hrhpv) testing alone every 5 years Co-testing with hrhpv in combination with cytology every 5 years Final Recommendation Statement: US Preventative Task Force JAMA. 2018;320(7): doi: /jama

40 The HPV FOCAL Randomized Clinical Trial Among women undergoing cervical cancer screening: Use of primary HPV testing compared with cytology testing Significantly lower likelihood of CIN3+ at 48 months Further research needed to understand the longterm clinical outcomes as well as costeffectiveness Ogilvie GS, van Niekerk D, Krajden M, et al.effect of screening with primary cervical HPV testing vs cytology testing on high-grade cervical intraepithelial neoplasia at 48 months: the HPV FOCAL randomized clinical trial. JAMA. doi: /jama

41 The HPV FOCAL Randomized Clinical Trial Implementation of HPV testing as a primary screen requires substantial patient education HPV infections are ubiquitous, may regress and can be followed without therapy, unless progressing towards cancer Declining prevalence of HPV disease following HPV vaccination will make the marginally better sensitivity of co-testing irrelevant Increased efforts of screening inadequately screened women will be necessary to make further progress against cervical cancer Massad,S, Replacing the Pap Test with Screening Based on Human Papillomavirus Assays, JAMA. Doi: /jama.2018

42 Countries Implementing HPV Primary Screening Netherlands: Minister of Health approved HPV primary screening beginning in 2016 Australia: National Health Service adopted screening with HV 16/18 genotyping starting at age 25 y at 5-yr intervals up to age United Kingdom: Evaluating in large national pilot study at 6 National Health Service screening sites including London, Liverpool, and Manchester. Italy: A number of regions have adopted primary screening Educate the Educators: ASCCP 2016

43 Age Appropriate Screening Must Continue in the Age of Vaccine!

44 Is Screening Needed After Vaccination? Yes!!! HPVv2 and HPVv4 vaccines protected against HPV 16 and 18 which cause 70 to 75% of all cervical cancers HPVv9 vaccine protects against HPV 16,18, and also types 31, 33, 45, 52, and 58 which cause 20% additional cancers Vaccination is for pre-exposure prophylaxis; most women will continue to rely on screening

45 Loss of Pap Screening Performance Due to Vaccination As successive cohorts of women are vaccinated: Reduction in prevalence of cytological abnormalities End result: decrease in positive predictive value of cytology Increase in false positive rates will lead to nonrigorous diagnostic work-up Impact on cytotechnician training and quality assurance Huh et al, Gyn Onc, 2010;Franco et al., Vaccine 2006

46 What is a Possible Paradigm Change in Screening Following Vaccination? Pap cytology will not be the same if left as primary test Potential solution: HR-HPV DNA testing as primary screening test followed by cytologic triage: HPV testing more upstream than cytology longer latency safety window HPV testing more sensitive and reproducible HPV testing less likely to vary in sensitivity and specificity Cytology will perform better in the artificially high lesion prevalence when triaging HPV+ women Huh et al, Gyn Onc, 2010;Franco et al., Vaccine 2006

47 Case Study Your 42-year old patient with no previous HPV screening was screened by you, using HPV testing alone. The patient is HPV (+) for HPV 16 and the panel of 12 other types How do you interpret this result? What is the next step in her management? Does she need a reflex to a Pap?

48 Case Study You are a colposcopist and bring her in for immediate colposcopy or refer her out for colposcopy. The colposcopy is adequate, as the squamocolumnar junction is seen 360 degrees around. There are no lesions to biopsy and an ECC is performed, which is reported as negative. What will you do next? How will you determine what you do next?

49 Case Study According to the consensus guidelines for managing abnormal cervical cancer screening tests and cancer precursors. 1. Women 25 to 65: Algorithm: Management of Women with No Lesion or Biopsy-confirmed Cervical Intraepithelial Neoplasia Grade 1 (CIN1) Preceded by Lesser Abnormalities FOLLOWUP WITHOUT TREATMENT Lesser Abnormalities Includes HPV 16+ or 18+ The management is cotesting in 12 months 1. Massad LS, et al updated consensus guidelines for the management of abnormal cervical cancer screening tests and cancer precursors. Obstet Gynecol. 2013;121(4):

50 Case Study The patient is cotested in 12 months. The results are NILM/HPV 16+. What will you do next? Massad LS, et al updated consensus guidelines for the management of abnormal cervical cancer screening tests and cancer precursors. Obstet Gynecol. 2013;121(4):

51 Case Study The patient will return to colposcopy. At the 12 month follow-up: if the Pap is ASC-US or HPV (+): Colposcopy is indicated. Massad LS, et al updated consensus guidelines for the management of abnormal cervical cancer screening tests and cancer precursors. Obstet Gynecol. 2013;121(4):

52 Cervical Cancer Screening Options for 2018 Attributes Cytology Cotesting HPV Primary Interval 3 years 5 years 3 years Age to start 21 years 30 years 25 years Complexity High Highest Low Level of Protection Moderate High High* Referrals to Colposcopy Lowest Higher Higher *Greater than cotesting if done q3 years vs q5 years for cotesting Wright, TC, Omnia, Webinar, 12/15

53 Future Goals Incorporate patient preferences regarding benefits and harms of alternate screening strategies Identifying a range of reasonable options Addressing variations in screening settings Patient preferences Cost analyses Sawaya, GF, Kuppermann M, Editorial, Identifying a Range of Reasonable Options for Cervical Cancer Screening. Obstet Gynecol 2015:125:

54 Potential Harms From Cervical Cancer Screening Anxiety from an abnormal test that the patient might fear to be a sign of cancer Stigma from diagnosis of a ubiquitous sexually transmitted infection (HPV) Time and patient expense related to screening and management Pain and injury from the procedures and treatment Increased risk of premature delivery and pregnancy loss Einstein, M, Cox, J.T., Cervical Disease, OBG Management, Vol.25, May 2013

55 What s to Know, What s New and What s Changed HPV Counseling

56 Counseling Women with HPV Remind your patient that: Most women will have HPV at some point. There is no way of knowing how long HPV has been present. Having HPV is not a sign of infidelity or promiscuity. more

57 Counseling Women with HPV (Continued) Most women who have HPV do not develop abnormal cells or cancer. Women who have HPV in their cells a long time are at greater risk for developing abnormal cells or cancer.

58 Messaging Educate women when they are being screened, about the role of HPV infection in cervical cancer You need an HPV test to determine if you have the virus Your son or daughter may be vaccinated to be protected from being infected by the types in the vaccine

59 Utilize Written Materials Helpful in supporting patient education Patients can use for later reference Many are available in additional languages including Spanish Unbranded materials: Center for Disease Control American Cancer Society American Society for Colposcopy and Cervical Pathology Association of Reproductive Health Professionals

60 Summary The 2012 Guidelines for cervical cancer prevention More benefit with least harm (over screening) Identifies low risk women (HPV and Pap negative) and reassures them about safety of longer screening interval Identifies truly at-risk women with persistent HPV Follow them diligently FDA approval of HPV testing as a primary screen, April 2014 Never has education of patients and practitioners been more important!

61 Summary HPV Testing in Primary Screening Interim Guidance has been published Are you ready? Will you perform stand alone HPV testing as primary screening?

62 Summary Majority of cervical cancer in U.S. occurs in women who have not been screened or infrequently screened Improving access to screening for these women will have a great impact on the prevention of cervical cancer!

63 Anal Cancer Screening

64 Anal Cancer Incidence relatively low compared with cervical cancer Incidence is increasing in both men and women by about 2% a year Reason for the increase is not well understood Men who have sex with men (MSM) shown to be one the populations at highest risk Anal receptive intercourse is a risk factor but is not necessary for anal cancer to develop Ferris DG, Cox JT, O Connor DM, Wright VC, Forester J. The anal canal and perianus: HPV-Related Disease. In Modern Colposcopy, Textbook and Atlas, 3 rd ed., 2012, Wolters Kluwer, Lippincott Williams & Wilkins. pg

65 Anal Cancer History of HPV associated lesions at genital sites other than the anus are associated with anal cancer Immunosuppression is an important risk factor for anal cancer Solid organ transplant recipients of heart, kidney and lungs HIV- associated immunosuppression Ferris DG, Cox JT, O Connor DM, Wright VC, Forester J. The anal canal and perianus: HPV-Related Disease. In Modern

66 HPV-Associated Anal Lesions High-grade precursor lesions called anal intraepithelial neoplasia (AIN) High prevalence of anal HPV infections and AIN in selected populations including MSM and HIV-infected individuals In one study 95% of 357 gay males had anal HPV and 50% had high-grade AIN Palefsky JM. AIDS

67 Anal Cancer Screening No national guidelines No randomized clinical trials Not yet a standard of care Ferris DG, Cox JT, O Connor DM, Wright VC, Forester J. The anal canal and perianus: HPV-Related Disease. In Modern Colposcopy, Textbook and Atlas, 3 rd ed., 2012, Wolters Kluwer, Lippincott Williams & Wilkins, pg

68 Anal Cancer Screening Anal screening Cytologic screening High resolution anoscopy (HRA) HRA directed biopsy Treatment of high grade anal intraepithelial neoplasia (HGAIN) aims to prevent invasive anal squamous cell cancer Ferris DG, Cox JT, O Connor DM, Wright VC, Forester J. The anal canal and perianus: HPV-Related Disease. In Modern Colposcopy, Textbook and Atlas, 3 rd ed., 2012, Wolters Kluwer, Lippincott Williams & Wilkins, pg

69 Screening for AIN and Anal Cancer Role of routine screening for AIN and anal cancer is controversial Advocates for screening note: Cytology is as effective for detecting anal disease as for cervical disease Cost-effective studies suggest anal screening is an attractive option Opponents note: Treatments for AIN often fail and there is no data that treatment prevents cancer CDC. MMWR (RR-8)

70 Current Status of Screening Recommendations Routine anal cytology screening is NOT recommended by CDC, USPSTF, ACS, or ISDA National Guidelines Clearinghouse has no guidelines for anal cytology screening However New York State Department of Health now recommends anal cytology for HIV-infected individuals who: 1) are MSM, 2) have had genital warts or 3) have had CIN New York State Dept of Health.

71 Anal Cytology Goal is to sample the surface epithelium of the entire anal canal Distal rectal vault to the anal sphincter Need to sample surfaces hidden inside the folds and invaginations of the canal Pathologists reading anal cytology require special training Ferris DG, Cox JT, O Connor DM, Wright VC, Forester J. The anal canal and perianus: HPV-Related Disease. In Modern Colposcopy, Textbook and Atlas, 3 rd ed., 2012, Wolters Kluwer, Lippincott Williams & Wilkins, pg

72 Anal Cytology: Technique Pt should refrain from anything into the anus for 24 hours before the procedure Use tap water moistened Dacron swab (not cotton) Do not use pre-scored swabs as they may snap at the score line Insert into canal until resistance is not met Above anal verge to distal rectum (3-4 cm) Rotate/apply pressure to walls of canal while removing sampling device (bends) slowly (count to 10) Ferris DG, Cox JT, O Connor DM, Wright VC, Forester J. The anal canal and perianus: HPV- Related Disease. In Modern Colposcopy, Textbook and Atlas, 3 rd ed., 2012, Wolters Kluwer, Lippincott Williams & Wilkins, pg

73 High Resolution Anoscopy (HRA) HRA is colposcopy of the anal canal and perianus Specific HRA/colposcopic criteria for low-grade and high-grade lesions based on biopsy of 385 lesions from 152 subjects first published by Naomi Jay in 1997 HRA-targeted biopsy is the gold standard for finding HGAIN occasionally SCCA HGAIN are potentially pre-cancerous lesions and identification and eradication may prevent anal cancer J. Michael Berry MD ASCCP Biennial Meeting 3/12

74 AIN Courtesy ARHP

75 Digital Anal Rectal Exam (DARE) Performed after the collection of the anal cytology and before HRA Goal is to detect any palpable abnormalities May guide further evaluation including the anoscopic examination and biopsies Ferris DG, Cox JT, O Connor DM, Wright VC, Forester J. The anal canal and perianus: HPV-Related Disease. In Modern Colposcopy, Textbook and Atlas, 3 rd ed., 2012, Wolters Kluwer, Lippincott Williams & Wilkins, pg

76 What Can Be Done to Manage Patients at Risk For Anal Cancer? Screening and treatment of cervical cancer precursors has effectively decreasing the incidence of cervical cancer by over 70% since screening began 50 years ago. The anus and cervix are similar tissues and are infected by the same cancer causing types of HPV and have the same types of lesions HGAIN is the precursor to anal cancer and can be identified and treated using HIGH-RESOLUTION ANOSCOPY or HRA J. Michael Berry MD ASCCP Biennial Meeting 3/12

77 IANS, International Anal Neoplasia Society, the world's first professional society devoted to prevention and treatment of AIN and anal cancer. IANS Mission IANS mission is to provide a forum for exchange of ideas and dissemination of knowledge regarding the pathogenesis, diagnosis, treatment and prevention of anal neoplasia among individuals with a broad spectrum of background, viewpoints and geographic origin.

78 Head and Neck Cancer HPV

79 Incidence in United States Women Men Total Oral cavity and pharynx 11,710 28,540 40,250 Larynx 2,520 9,840 12,360 Total 14,230 38,380 52,610 American Cancer Society. Facts & Figures

80 Differences HPV positive HPV negative Site Tonsil, base of tongue Various sites Age Younger Older Risk Sexual behavior Tobacco, alcohol Incidence Increasing Decreasing Survival Better Worse Vidal L. Hematol Oncol Clin N Am

81 Oropharyngeal Cancer Located in middle of the throat: base of the tongue, tonsils, soft palate, walls of the pharynx. No precursor lesions or biomarkers Data does not support the role of saliva tests Often presents as lymphadenopathy with the cancer deep in the tonsillar crypts Oral HPV or cancer in monogamous couples: no current recommendation to change behavior Oral Presentation: D Souza, G., ASCCP Annual Meeting. April 20, 2018.

82 Presentation Neville BW. CA Cancer J Clin.2002.

83 American Cancer Society Guidelines the cancer-related check-up should include examination for cancers of the thyroid, testicles, ovaries, lymph nodes, oral cavity, and skin, as well as health counseling... Smith RA. CA Cancer J Clin

84 So In Closing..

85 NOBODY WANTS WARTS.. Courtesy Richard Reid MD

86 NOBODY WANTS CANCER. Courtesy Richard Reid MD

87 SO LET S GET BUSY!!!!

88 Courtesy Richard Reid MD

89 THANK YOU! QUESTIONS?

90 References 1. Saslow D, et al. American Cancer Society, American Society for Colposcopy and Cervical Pathology, and American Society for Clinical Pathology screening guidelines for the prevention and early detection of cervical cancer. J Low Genit Tract Dis. 2012;16(3): Walboomers JM, et al. Human papillomavirus is a necessary cause of invasive cervical cancer worldwide. J Pathol. 1999;189(1): Huh WK, et al. Use of primary high-risk human papillomavirus testing for cervical cancer screening: interim clinical guidance. Obstet Gynecol. 2015;125(2): Massad LS, et al updated consensus guidelines for the management of abnormal cervical cancer screening tests and cancer precursors. Obstet Gynecol. 2013;121(4): Hamborsky J KA, Wolfe S, eds. Epidemiology and Prevention of Vaccine-Preventable Diseases. 13 th ed. Washington, DC: Public Health Foundation; Ho GY, et al. Natural history of cervicovaginal papillomavirus infection in young women. N Engl J Med. 1998;338(7): Ho GY, et al. Persistent genital human papillomavirus infection as a risk factor for persistent cervical dysplasia. J Nat Cancer Inst. 1995;87(18):

91 References 8. Moscicki AB, et al. Chapter 5: Updating the natural history of HPV and anogenital cancer. Vaccine. 2006;24(Suppl 3):S3/ Schiffman M, Kjaer SK. Chapter 2: Natural history of anogenital human papillomavirus infection and neoplasia. J Natl Cancer Inst Monogr. 2003(31): Jemal A, et al. Annual Report to the Nation on the Status of Cancer, , featuring the burden and trends in human papillomavirus(hpv)-associated cancers and HPV vaccination coverage levels. J Nat Cancer Inst. 2013;105(3): Wright TC Jr., et al. Interlaboratory variation in the performance of liquid-based cytology: insights from the ATHENA trial. Int J Cancer. 2014;134(8): Ciavattini A, et al. Loop electrosurgical excision procedure and risk of miscarriage. Fertil Steril. 2015;103(4): Jin G, et al. Pregnancy outcome following loop electrosurgical excision procedure (LEEP) a systematic review and meta-analysis. Arch Gyn Obstet. 2014;289(1): Ronco G, et al. Efficacy of HPV-based screening for prevention of invasive cervical cancer: follow-up of four European randomised controlled trials. Lancet. 2014;383(9916): Wright TC Jr., et al. Evaluation of HPV-16 and HPV-18 genotyping for the triage of women with highrisk HPV+ cytology-negative results. Am J Clin Pathol. 2011;136(4): Ronco G, et al. HPV16 and HPV18 genotyping in cervical cancer screening. Lancet Oncol. 2011;12(9):

92 References 19. Wright TC, et al. Primary cervical cancer screening with human papillomavirus: end of study results from the ATHENA study using HPV as the first-line screening test. Gynecol Oncol. 2015;136(2): Wright TC, Jr., et al. The ATHENA human papillomavirus study: design, methods, and baseline results. Am J Obstet Gynecol. 2012;206(1):46.e41-46.e Cox JT, et al. Comparison of cervical cancer screening strategies incorporating different combinations of cytology, HPV testing, and genotyping for HPV 16/18: results from the ATHENA HPV study. Am J Obstet Gynecol. 2013;208(3):184 e e Stoler MH, et al. Point-Counterpoint: Cervical Cancer Screening Should Be Done by Primary Human Papillomavirus Testing with Genotyping and Reflex Cytology for Women over the Age of 25 Years. J Clin Microbiol. 2015;53(9): Blatt AJ, et al. Comparison of cervical cancer screening results among 256,648 women in multiple clinical practices. Cancer Cytopathol. 2015;123(5): Gage JC, et al. Reassurance against future risk of precancer and cancer conferred by a negative human papillomavirus test. J Nat Cancer Inst. 2014;106(8). 25. Qaseem A, et al. Screening pelvic examination in adult women: a clinical practice guideline from the American College of Physicians. Ann Intern Med. 2014;161(1): Practice Bulletin No. 157: Cervical Cancer Screening and Prevention. Obstetrics and gynecology. 2016;127(1):e1-e20.

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