HPV-related papillomatous-condylomatous lesions in female anogenital area

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1 HPV-related papillomatous-condylomatous lesions in female anogenital area Theo Panoskaltsis MD, FRCOG, CCST (UK)

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3 Epidemiology Anal cancer is increasing in both men and women Groups at risk: - HIV (+) men and women - HIV (-) MSM - HIV (-) women at high risk of aquiring HIV - patients with immunosuppression Frisch M et al N Engl J Med 1997

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5 History of receptive anal intercourse Risk factors External genital warts Number of sexual partners, Smoking History of cervical cancer, CIN, Vulvar Ca, VIN

6 Primary aetiologic factor that cervical and anal cancer share is HPV Anal intercourse is NOT an absolute requirement to aquire anal HPV infection

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9 27% Anal HPV prevalence in HIV(-) women The Hawaii study Hernandez et al, 2005

10 HPV 16, the most common type

11 Who should be screened? Men and women HIV (+) MSM Patients with immunosuppression, (organ transplant) Women with lower genital tract HPV disease (VIN, CIN) Men and women with perianal condylomata Edgren G et al Lancet Oncol 2007

12 Anal Cytology Anal synthetic brush (Dacron swab), inserted to, at least, 4 cm inside canal Glass-fixed slides or Liquid-based Cytology Standard Papanicolaou technique Haematoxylin-Eosin staining

13 Conventional cytology Specimen contaminated by bacteria

14 Anal liquid-based cytology LSIL AIN HSIL AIN

15 Bethesda criteria

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17 Better performed with a colposcope (magnify > 20 times) High-resolution Anoscopy Landmark the transformation Zone (Rectal columnar epithelium meets Anal squamous epithelium)

18 Anoscopic technique Biopsy of suspicious areas Gauze pad soaked in 3% acetic acid in anal canal, left for 3 min Terminology as in colposcopy (aceticwhite, mosaic, abnormal vessels etc)

19 Magnifying lenses are inadequate for anoscopy

20 Plastic disposable anoscopes

21 Anoscopic technique

22 Dorsal Position Standard colposcope

23 Anoscopic technique Biopsy of suspicious areas

24 Peri-anal and Intra-anal Warts should, always, be biopsied before treatment External AIN 3

25 Paget s Disease

26 Normal anal TZ

27 A/W1 Condyloma

28 Diffuse A/W1 Condyloma at 7 o clock

29 AIN 1, staining with lugol s solution

30 Various degrees of AIN

31 Keratinised AIN (may harbour HSIL)

32 Distinct margins AIN 2

33 HSIL (mosaic-punctation) at 4 o clock

34 Vascular punctation

35 Mosaic pattern

36 Atypical vessels

37 Neo-vascularisation Suspicion of invasive cancer

38 AIN 3

39 Punctation and mosaic AIN 3

40 Coarse punctation and mosaic early invasive Ca

41 Superficially invasive Ca

42 Denuded epithelium invasive Ca

43 Friable, palpable mass invasive Ca

44 baby Tischler Forceps

45 AIN1 Haematoxylin-Eosin Immunohistochemistry (P16 HPV E7 oncogene expression)

46 AIN 2-3 Haematoxylin-Eosin Immunohistochemistry (P16 HPV E7 oncogene expression)

47 AIN3 (in-situ) Haematoxylin-Eosin Immunohistochemistry (P16 HPV E7 oncogene expression)

48 Risk of cancer with AIN3 in healthy individuals Approximately 1:10 Scholefield et al, Br J Surg, 2005

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50 Chemical ablation TCA (trichloroacetic acid) Podophyllin Imiquimod

51 Electrocautery Physical ablation Infrared coagulation (IRC) - heat from light source directed through a probe - coagulates instead of burning - office procedure Cryotherapy - used for external disease - more than one session Laser therapy

52 Surgical treatment In suspicion of invasion Anal TZ CANNOT be completely excised Usually combined treatment (excision + ablation) Stenosis and incontinence most serious complications Most recurrences in HIV (+) pts

53 AIN Treatment 1. Therapeutic Vaccine

54 AIN Treatment 2. Ablative treatments

55 AIN Treatment 3. Surgical excision

56 AIN Treatment 4. Immunostimulants (ALDARA)

57 ALDARA Complete resolution after 16 weeks

58 AIN recurrence after treatment

59 AIN recurrence after Treatment Trichloroacetic Acid 75% Surgical excision 79% Infrared Coagulation 65% 5-FU 50%

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61 Probability of recurrence is related to immunocompetence (HIV) status

62 Future for HPV-related cancers?

63 A variety of doctors see HPV patients

64 Future? Certification for Diagnosis and Treatment of HPV related anal conditions Gynaecologists, Gastroenterologists, Colorectal surgeons could run specialist clinics Collaboration with medical and radiation oncologists Work with an expert pathologist

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68 Is Vaccination the answer to all HPV-related cancers?

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70 Anal Cytology should be followed by Anoscopic biopsy Compared to Histology, Cytology has a 60% sensitivity and specificity for detecting AIN and, specifically, for HSIL (AIN 2,3) sensitivity of only 16%

71 Anal cancer risk in HIV (+) Pre - HAART 11-19/100,000 Post - HAART 40-78/100,000 VIN3 AIN3

72 50% long-term recurrence

73 With 5-FU, reduction in viral load, irrespective of response to tx

74 USA