HPV Infection in Fe-male Patients: Methods of Detection. Topics. West Coast Pathology Laboratories WEST COAST PATHOLOGY LABORATORIES

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1 WEST COAST PATHOLOGY LABORATORIES HPV Infection in Fe-male Patients: Methods of Detection John Compagno, MD, Medical Director Topics Pap cytology still an excellent test made better Value of HPV Genotyping Specific HPV types associated with CIS 3q26 gain HPV induced somatic mutation associated with Cervical Carcinoma Anal and Oral carcinoma relationship to cervical HPV infection Collection Methods West Coast Pathology Laboratories 1

2 WCPL LIQUID BASED CYTOLOGY 2

3 27 Routine Pap 27 Routine Pap 3

4 HPV 66, 17 yo 4

5 Co-Testing: HPV, Pap 5

6 Topics Pap cytology still an excellent test made better Value of HPV Genotyping Specific HPV types associated with CIS Anal and Oral carcinoma relationship to cervical HPV infection 3q26 gain association with Cervical Carcinoma Polymerase Chain Reaction HPV DETECT 6

7 WCPL HPV VIRUS ID (GENOTYPING) 7

8 HPV 16 HPV 31 HPV 52 HPV 58 HPV 33 HIGH GRADE DYSPLASIA 545 Patients: % of High Grade Dysplasia (82,59,35,66) (note: 253 were <30 years of age) 307 cases of CIN III in 2010! 24/307 (7.8 %) under age /307 (48.2%) under age 30 33/307 (10.7%) HPV negative 37% HPV-16 48% 11% HPV-31 8% HPV-58 68% 8% HPV-52 4% HPV-18 30% HPV- Other Increased accuracy!! WCPL: TOTAL # OF HPVS: 144,456 POS: 29,414 = 20% NEG: 115,456 = 80% POS 2: 5500 = 20% 8

9 HIGH GRADE DYSPLASIA 1381 Patients: HPV 16 HPV 31 HPV 52 HPV 58 70% of High Grade Dysplasias (53,66,18,33,59) (note: 656 were <30 years of age) HPV Family Tree Specific Oncogenic Region 9

10 1381 Cases of CIN III by 2012! 92/1381 (6.7 %) under age /1381 (48 %) under age 30 35/1381 ( 2.5 %) low-risk viruses only 139/1381 (10 %) HPV negative 44% HPV-16 11% HPV-31 70% 10% HPV % HPV-58 * HPV 18 = 3.8% Low Risk Viruses: Who cares?? The presence of identifiable low risk viruses is a marker for infection by HPV viruses and may reflect the presence of high risk viruses that are not replicating at the time of sampling. Report or do not report?? 10

11 Sokolova et al., Journal of Molecular Diagnostics, Vol. 9, No. 5, November

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13 3 q 26: What is in this Mutation/Gene? Contains sequences for the RNA component of the Human telomerase (TERC) gene which serves as a template for telomere addition, the basis of telomerase-based cell mitotic activity and immortalization. 3q 26 Gain: Somatic HPV Induced Mutation HPV Determines Risk of Disease 3q 26 Gain Detects the Disease 3 q 26 GAIN - BIOMARKER HPV induced Somatic Mutation that predicts disease progression, i.e. CIN I CIN III 3q gain represents a pivotal genetic change that precedes invasive carcinoma. FISH technology allows detection NPV = >99% 13

14 Chromosomal Instability OncoFish Cervical testing detects chromosomal instability at a numerical or structural level, which is the hallmark of malignancy. 14

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17 Topics Pap cytology still an excellent test made better Value of HPV Genotyping Specific HPV types associated with CIS Anal and Oral carcinoma relationship to cervical HPV infection. Collection 3q26 gain association with Cervical Carcinoma 17

18 ANAL CYTOLOGY ANAL DENTATE LINE 18

19 Anal Cytology Collection Rotate swab in a circular fashion like a cone (use sphincter as fulcrum) as it is withdrawn in order to sample cells from all aspects of anal canal Anal Carcinoma Unlike cervical cancer, ANAL cancer is on the rise. Incidence rates.have jumped by 78 percent in women.probably because more people now have more sexual partners and more people have anal sex....says Lisa Johnson, a cancer epidemiologist at the Fred Hutchinson Cancer Research Center in Seattle who led the 2004 study. 19

20 Recent studies..results suggest that analhpv infection is a common infection among healthy, sexually active females with prevalence comparablewith cervical infection anal and cervical HPV strongly correlated..those with cervical infection have >3-fold risk of anal infection and 13% of healthy women are infected in both anatomic sites. [ Anal HPV Infection in Women Relation to Cervical Infection. Cancer Epidemiol Biomarkers Prev 2005;14(11), November 2005 MALIGNANT ANAL TUMORS Serotype HPV-16appear to have the most frequent associationwith high-grade anal intraepithelial neoplasia (AIN) and anal cancer. Increased risk: history of cervical or vulvar CIS Increased risk: history of cigarette smoking Increased risk: Anal receptive intercourse No increased risk with hemorrhoids, fissures, fistulas, or inflammatory bowel disease 20

21 Oropharyngeal Carcinoma 21

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23 HPV Detection in Oral Cavity HR-HPV in the Oral Cavity of Women with Cervical Cancer, and Their Children. Saini et al. Virology Journal 2010, 7:131 Low if any risk of HR-HPV Oral infection Asymptomatic Oral HPV Infection in Women with a Histopathologic Diagnosis of Genital HPV. Journal of Oral Science, Vol.53, No. 4, 2011.at high risk for subclinical oral HPV infection. Oral/Oropharyngeal HPV Prevalence: 7% ( : 10%, : 3%) lower than reported prevalence of anogenital Associations: Sexual contact (8X), Smoking Bimodal age distribution in but not Prevalence of HPV 16 ( 5X in ) 1% (~2M) Effects of smoking: immunosuppression, Efficiency of transmission: Casual contact unlikely to transmit HPV Topics Pap cytology still an excellent test made better Value of HPV Genotyping Specific HPV types associated with CIS 3q26 gain HPV induced somatic mutation associated with Cervical Carcinoma Anal and Oral carcinoma relationship to cervical HPV infection 23

24 SciTranslMed 9 January 2013: Vol. 5, Issue 167, p. 167ra4 Sci. Transl. Med. DOI: /scitranslmed Research Article Ovarian Cancer Evaluation of DNA from the Papanicolaou Test to Detect Ovarian and Endometrial Cancers Isaac Kinde1,*, ChetanBettegowda1,2,*, YuxuanWang1,*, JianWu1,3,, HPV & CT/NG TESTING IN MALES NOW AVAILABLE!! (PCR) TESTING IN MALES SENSITIVITY DEPENDENT ON NUMBER OF CELLS. SPECIFICITY VERY HIGH. REQUIRES SAMPLE OF SHAFT/GLANS/CORONA USE RED SWAB Suggestions Give serious consideration to baseline HPV in sexually active women irrespective of age Give some thought to the potential risk of anal infection with HPV in sexually active patients. Higher risk in those with cervical infection. Realize that specific viruses can add substantial risk of HSIL/CIS and that the Pap smear is a good way to follow patients. 24

25 Milton Friedman: Capitalism & Freedom 1962 Subject matter for discussion, consider the issues, turn them over in your mind.at leisure... circumstances make change necessary. There is enormous inertia, i.e The Tyranny of the Status Quo. When the unthinkable becomes inevitable. THE END Time for Questions?? Thank You!! 25