Pre-invasive Lesions of the Lower Genital Tract.pptx

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1. Pre-invasive Lesions of the Lower Genital Tract By dr. chaltu

2. Most follow HPV infection( High risk) Precursor to invasive cancer=>doesn’t develop De novo Arise from the transformation zone of the cervix Detected early by screening, before cancer develops Introduction

3. In the LGT, the term intraepithelial neoplasia refers to epithelial lesions that are potential precursors of invasive cancer. These lesions demonstrate a range of histologic abnormality from mild to severe based on cytoplasmic , nuclear, and histologic changes. LOWER GENITAL TRACT NEOPLASIA

4. The severity of squamous intraepithelial lesions is graded by the proportion of epithelium with abnormal cells. Cervical intraepithelial neoplasia (CIN1) or mild dysplasia :- abnormal cells solely confined to the lower third of the squamous epithdium . CIN 2 or moderate dysplasia:- Those that extend into the middle third.

5. CIN 3 or severe dysplasia :- into the upper third Carcinoma in situ (CIS):- full-thickness involvement Pre-invasive squamous lesions of the vagina, vulva, perianal , and anal squamous epithelia are graded similarly to CIN.

6. Currently the Bethesda System cytologic nomenclature replaced CIN with squamous intraepithelial lesion (SIL). Because cytologic and histologic changes of HPV infection and CIN 1 are not distinguished reliably. they are categorized together as low-grade squamous intraepithelial lesions (LSIL).

7. CIN 2, CIN 3, and CIS are difficult to distinguish, are truer cancer precursors, and are designated together as high-grade squamous intraepithelial lesion (HSIL).

8. Vagina- lined by nonkeratinized squamous epithelium. Cervix Squamocolumnar Junction during embryogenesis, upward migration of stratified squamous epithelium from the urogenital sinus is thought to replace miillerian epithelium. ANATOMIC CONSIDERATIONS

9. This process usually terminates near the external cervical os , forming the original squamocolumnar junction (SCJ). The location of the SCJ varies with age and hormonal status. During the reproductive years, it everts outward onto the ectocervix in response to estrogen ( during adolescence, pregnancy, and COC use).

10. It regresses into the endocervical canal with the process of squamous metaplasia and Iow -estrogen states like menopause, lactation,& progestin-only contraceptive use. Squamous Metaplasia At puberty →↑estrogen →↑ glycogen → vaginal flora to be dominated by lactobacilli → acidic vaginal pH → squamus metaplasia (r eplacement of columnar by squamous epithelium on the cervix).

11. 5/29/2023 11 Squamous meta….

12. squamous metaplasia is most active during adolescence and pregnancy. Nearly all cervical neoplasia , both squamous and columnar, develops within the TZ, usually adjacent to the new or current SCJ. Cervical reserve and immature metaplastic cells are most vulnerable to the oncogenic effects of HPV and co-carcinogens.

13. Human papillomavirus infection (HPV) – Primary factor Sexual behavior, Smoking HIV infection, Chlamydia infection Oral contraceptive Multiple pregnancies Sexual activity and first pregnancy at earlier age Low socioeconomic status Diethylstilbestrol (DES) Source: Amer lmmunosuppression 5/29/2023 13 Risk Factors

14. HPV causes nearly all cervical cancers and approximately 90% of anal cancers, 70% of vaginal, and 40% of vulvar cancers. HPV primarily infects human squamous or metaplastic epithelial cells. Non-enveloped, double-stranded DNA virus. There are more than 150 types of HPV. HUMAN PAPILLOMAVIRUS INFECTION

15. Clinically, HPV types are classified as high-risk ( hrHPV ) or low-risk { lrHPV ) LrHPV types 6 and 11 cause nearly all genital warts & laryngeal papillomaa Fifteen of the 150 variants are considered as high risk. Out of these eight ( HPV-16,18,31,33,35,45,52 & 58) are commonly identified in cervical cancer.

16. HPV-16 & 18 are the commonest ( involving 70 % of all cancer cases). HPV 16 is the most oncogenic and accounts for the largest percentage of CIN3 lesions (45%) and cervical cancers (55%). HPV -31,33,45,52,& 58 –accounts for 15% -20% of all cancer cases The rest seven (HPV-39, 51, 56, 59, 66, 68, &73) less certain on their contribution 5/29/2023 16 HPV…

17. High-risk HPV infection is most common in young women, with a peak prevalence as high as 25–30% in women under 25 years of age . They are differentiated by their viral genes ( Early-E,& late-L=> especially E6,E7 & L1;which are considered as basic genes for viral infection & cancer development).

18. Infection with high risk HPV Persistence of the infection Progression of infected epithelium to precancerous lesion If untreated, invasive lesion Steps of disease progression

19. 5/29/2023 19 HPV…

20. Most HPV infection and related lesions, whether clinical or subclinical, spontaneously resolve, especially in adolescents and young women.

21. 1.Behavior Sexual abstinence delaying coitarche and limiting the number of sexual partners Infection Prevention=(primary)

22. 2.HPV Vaccines HPV-vaccines are DNA-free capsids ( capsid protein –L1). They induce cellular & humoral ( Ab ) immune response. They prevent new HPV infection by blocking its entry into the host cells. Three HPV vaccines are currently available: bivalent , Quadravalent , and nonavalent

23. 1 . Cervarix ( HPV-16 & 18 ),prevents only the high grade lesions prevents cervical cancer in 70 % of cases 2.Gardacil 4 (HPV-6,11,16,&18) prevents both cervical cancer and low grade lesions ( warts ) in 90 % of cases. 3.Non-valent vaccine( Gardasil 9) , which includes 9 genotypes of HPV- 16, 18, 6, 11, 31, 33, 45, 52 and 58 with the cervical cancer preventive potential of 96%

24. FDA approved that HPV vaccine be administered routinely to all girls and boys aged 11 to 12 years (as early as age 9 years). Catch-up vaccination is also recommended for all 13- to 26-year-old persons. Three doses of vaccines ( at 0,1-2 mo,& 6 months) usually given.

25. HPV vaccination has the potential to prevent malignancy for at least six body sites that include cervix, vulva, vagina, penis, anal canal, and oropharynx .

26. Screening ( secondary prevention) for precancerous lesions New programs (WHO) should start by screening women aged 30 years or more. Age group 25–49 years, a three-year interval Over 50 years, a five-year screening interval If resources are limited, screening every 5–10 years – or Even just once between the ages of 35 and 45 years – will significantly reduce deaths from cervical cancer CERVICAL INTRAEPITHELIAL NEOPLASIA DIAGNOSIS

27. Women with prior treatment for CIN 2, CIN 3, AIS, or cervical cancer should continue screening for at least 20 years. With HIV infection, screening should commence within 1year of sexual activity onset and then annually.

28. Discontinue after the age of 65 years two negative results after three consecutive cytologies or co-tested with HPV-DNA in the last 10 years, at least one in the last 5 years There shouldn’t be any history of treated HSIL, AIS, or cancer. If she had total hysterectomy for other conditions other than high grade lesions.

29. 1.Cytology ( Pap smear) Famous after Zoologist George Papnicolaou (1883-1962). Conventional method (cytology) Vs Liquid –based cytology several studies have shown that LBC is more sensitive than CM and has almost the same specificity. Screening modalities

30. It is associated with high false negative result ( low specificity,50-60 %),so it needs frequent tests not to miss abnormal changes Unsatisfactory cytology needs to be repeated after 2-4 months The abnormal cytologies are classified (according to the Bethesda system) :

31. Squamous cell 1. Atypical squamous cells of undetermined significance (ASC-US) => High grade HPV test is recommended or repeat test after a year . 2. Atypical squamous cells cannot exclude HSL (ASC-H )=> colposcopic examination regardless of HPV test. It is a rare finding (only 10 % )of ASC, High number of cases ( 30-50 % ) have found to harbor CIN-II & III in subsequent follow up biopsy. The 2014 Bethesda System: Epithelial Cell Abnormalities

32. 3. Low-grade squamous intraepithelial lesion( LSIL)=> mild dysplasia, & cellular infection with HPV ( Koilocytosis ). <2 % of cases progress to invasive cervical ca 15-20 % of HSIL on subsequent biopsy ,if left untreated, Colposcopic examination with/without HPV test. If HPV negative, co-test after a year

33. 4. High-grade squamous intraepithelial lesion ( HSIL) => moderate dysplasia, sever dysplasia, & squamous cell carcinoma in situ. colposcopic examination regardless of HPV test. It needs immediate treatment 5.Squamous cell carcinoma=> malignant cells in a background of necrotic derbies, blood ,& inflammatory cells.

34. Glandular cell 1.Atypical: Endocervical cells, endometrial cells, glandular cells (AGC) 2.Atypical, favor neoplastic : Endocervical , glandular (AGC) 3.Endocervical adenocarcinoma in situ {AIS) 4.Adenocarcinoma Endocervical , endometrial, extrauterine , not otherwise specified

35. In all (endometrial sampling can be considered if she is >35 years old or younger with high risk of endometrial cancer) needs colposcopy & endocervical sampling .

36. 2.HPV testing It is more sensitive & reproducible than cytology. Started at the age of 30 years & repeated Q 5 years. It can be used for different purposes As a test of cure, following treatment of high grade lesions Triage of test( ASCU, &LSIL) Primary HPV screening Co-test with cytology

37. 3.Visual inspection ( VI ) Have better specificity & sensitivity compared to cytology Better suits in the recourse limited settings Biopsy can be taken on the abnormal areas=> directed biopsy Doesn’t need frequent visits-once/twice in life time, at age range of 30-39 years

38. VI with acetic acid (VIA)= 3-5 % Dehydrates cells with large nucleus=>reflects light=> acetowhite epithelium Abnormal vascularities are also seen

39. VI with lugol’s iodine ( VILI) =4-5 % normal cell has high glycogen=> Deep brown Abnormal cells => Yellow due to low glycogen Better used to evaluate the vaginal wall

40. 4.Colposcopy is a device that uses illumination (through light source) & magnification ( early days 3.5x-30x) ,that can identifies smaller lesions with better characterization than the naked eyes. There are two major types of colposcopes : traditional optical (uses binocular optics) colposcope ,& the newer video colposcope

41. Identifies transformation zone & the lesion with guided biopsy Costly & needs trained personnel 5. BIOPSY Cervical biopsy Endocervical brushing/Curettage

42. The natural history of cervical HPV infection , cervical cancer precursors &Future pregnancy implication of treatment ASC-US, & LSIL=>Q 6-12 months following HPV-DNA test & colposcopic examination. Biopsy can be considered CERVICAL INTRAEPITHELIAL NEOPLASIA MANAGEMENT

43. ASC-H-make colposcopic examination. If CIN –II/ III,treat accordingly. HSIL- colposcopy with directed biopsy. If biopsy shows CIN-II/III- treat ,even if she is an adolescent . Treatment can be delayed if she is pregnant

44. CIN 1 The spontaneous regression rate of biopsy-proven CIN 1 is 60% to 85%. The regressions typically occur within a 2-year follow-up with cytology and colposcopy .

45. Generally => Ablative & Exicisional procedures. After treatment she has to be followed till 20 years, even if she passed age of 65 years 1.Ablation therapy - Cryotherapy , electrocoagulation diathermy,& CO2 laser ablation Modes of treatment

46. Cryotherapy :- is destruction by cryonecrosis of the lesion through hypothermia. It uses liquid N2O, which creates ice ball on the lesion. 2.Excisional procedures: - Loop Electrosurgical Excision Procedure(LEEP), Excisional conization (cold-knife conization ), CO2 laser excision, & total hysterectomy.

47. Post-treatment surveillance with cytology, HPV testing, and/or colposcopy is required to confirm treatment success. After treatment for HSL or invasive cancer, screening continues for at least 20 years, even if screening extends beyond age 65. Surveillance after Treatment or Regression

48. Primary vaginal carcinoma is rare and makes up <5% of all gynecologic malignancies. 90% of vaginal cancers are squamous cell carcinomas. These appear to develop slowly from precancerous epithelial changes, called vaginal intraepithelial neoplasia ( ValN ), in a fashion similar to cervical cancer from CIN. VAGINAL INTRAEPITHELIAL NEOPLASIA

49. V aIN demonstrates histopathology similar to CIN. It is rarely found as a primary lesion and most often develops as an extension of CIN, mainly in the upper third of the vagina. Unlike the cervix, the vagina lacks a TZ that is susceptible to HPV-induced neoplasia . HPV DNA was found in up to 98% of VaIN lesions.

50. VaIN is asymptomatic and abnormal cytology results are often the first indication. Diagnosis is similar to CIN. Diagnosis

51. Low-Grade ValN LSIL often represent atrophy or transient HPV infection. Spontaneous regression is common. No treatment Management

52. High-Grade ValN Options of mgt - Wide local excision -C02 laser ablation Topical therapy- 5% fluorouracil (5-FU) cream Radiation therapy

53. Vulvar cancer is rare and 6% of all gynecologic cancers. Of vulvar cancers, 90% are squamous cell and in some cases may develop slowly from VIN. The vulva, unlike the cervix, has no TZ, and the effect of HPV infection on the vulva's keratinized epithelium is not biologically comparable to that on the cervix. VULVAR INTRAEPITHELIAL NEOPLASIA

54. Compared with CIN, VIN less often progresses to high grade disease and cancer. VIN now has three categories of squamous intraepithelial lesions (SIL): 1. Vulvar LSIL FormerlyVIN 1, HPV effect, Flat lesions with basal atypia and koilocytic changes such as condyloma Self-limited lesions, not precancerous

55. 2. Vulvar HSIL Formerly VIN usual type (VIN 2, VIN 3,vulvar CIS) Younger women Multicentric and multifocal disease Oncogenic HPV infection common Cigarette smoking, other STDs, immunosuppression

56. 3. Differentiated VIN Unproven but likely precursor to most vulva squamous cell carcinoma Older, postmenopausal women Unicentric and unifocal disease Oncogenic HPV infection uncommon Associated with vulvar dermatologic conditions such as lichen sclerosus .

57. Clinical Findings VIN may be asymptomatic and discovered with routine gynecologic examinations or during evaluation of abnormal cervical or vaginal cytology results. No screening strategies are available for vulvar HSIL detection. signs and symptoms: itching, burning, and pain. Diagnosis

58. clinically significant vulvar HSIL lesions are often visible without the aid of special techniques. They may be white, hyperkeratotic plaques; hyperpigmented lesions; or erythematous areas. most suspicious focal vulvar lesion are biopsied.

59. Selection of the best location to biopsy is aided by magnification of the vulva, perineum, and perianal skin, usually with a colposcope ( vulvoscopy ) . Vulvar epithelial changes are enhanced by applying a 3- 5% acetio -acid-soaked gauze pad to the vulva for 5 minutes prior to vulvoscopy .

60. Vulvar LSIL self-limited and not precancerous and is not tteated unless symptomatic, such as with a gross condylomatous lesion. Vulvar HSIL is a premalignant condition that can progress to vulvar cancer. Standard options are local destruction or excision. Management

61. wide local excision (WLE) Laser ablation Topical therapy

62. Thank U!