Presentation on theme: "Cervical Cancer DR KHALID H. WALI SAIT (FRCSC)"— Presentation transcript:
1Cervical Cancer DR KHALID H. WALI SAIT (FRCSC) 1920 colposcopy1930 was used in EuropeUSAACCSPSHORT FOCAL LENGTH CAN NOT DO BIOPSYLONG FOCAL LENGTH NOT COMFORTABLE PERFORM BIOPSY5 % UNSATSF COLPOSCOPYDR KHALID H. WALI SAIT (FRCSC)ASSOCIATE PROFESSOR OF GYNECOLOGICAL ONCOLOGYKing Abdulaziz University Hospital, Jeddah, Saudi Arabia
2Worldwide cervical cancer rates are high, particularly in developing countries. According to information published by WHO in 2003:1Cervical cancer is the second most common cancer (after breast cancer) among women worldwide.Approximately 80% of new cases are reported from developing countries.Worldwide prevalence is estimated at 2,274,000 cases, with approximately 510,000 new cases reported each year. Canada, in contrast, had an estimated incidence of 14,845 cases inWithout screening programs (i.e., routine Pap smears), cervical cancer is detected too late and leads to death in almost all cases.1ReferencesWorld Health Organization. State of the art of new vaccines research and development: Initiative for vaccine research. Geneva, Switzerland: World Health Organization; 2003:1–74.Bosch FX, de Sanjose S. Chapter 1: Human papillomavirus and cervical cancer—burden and assessment of causality. J Natl Cancer Inst Monogr. 2003;(31):3-13.
3Cancer in WomenWorld Wide Breast Colo-rectal Cervix and Uterus Lung Leukemia-Lymphoma OvarySaudi Breast Thyroid Leukemia–Lymphoma Colo-rectal Ovary Liver Cervix Uterus
5Pathogenesis HPV are etiological agent for cancer cervix HPV DNA can be found in 99.7 % of all cervical carcinomaType 16, 18, 45 and 31 most frequent.Several epidemiological and molecular studies over two decays
6HPV Nonenveloped double-stranded DNA virus1 >100 types identified2 ~30–40 anogenital2,3~15–20 oncogenic*,2,3 types, including 16, 18, 31, 33, 35, 39, 45, 51, 52, 584HPV 16 (54%) and HPV 18 (13%) accounted for the majority of worldwide cervical cancers.5Nononcogenic** types include: 6, 11, 40, 42, 43, 44, 544HPV 6 and 11 are most often associated with external genital warts.3Key PointThere are many different types of HPV; of the ~15–20 oncogenic types, HPV 16 and HPV 18 account for the majority of cervical cancers.BackgroundPapillomaviruses such as HPV are nonenveloped, double-stranded DNA viruses.1 More than 100 HPV types have been detected,2 with >80 types sequenced and classified.3 Approximately 30–40 types of HPV are anogenital, of which ~15–20 types are oncogenic.2,3 In an international meta-analysis (n = 10,058 invasive cervical cancer cases from 85 studies), HPV Types 16 and 18 are oncogenic and account for about two thirds of all cervical cancers—the next 5 most prevalent types (31, 33, 45, 52, 58) account for an additional 18% of cases.4 Other oncogenic HPV types include 35, 39, 51, and 56.5 HPV Types 6 and 11 are nononcogenic and are associated with external genital warts.3References1. Howley PM. Papillomavirinae: The viruses and their replication. In: Fields BN, Knipe DM, Howley PM, eds. Fields Virology. 3rd ed. Philadelphia, Pa: Lippincott-Raven; 1996:2045–2076.2. Schiffman M, Castle PE. Human papillomavirus: Epidemiology and public health. Arch Pathol Lab Med. 2003;127:930–934.3. Wiley DJ, Douglas J, Beutner K, et al. External genital warts: Diagnosis, treatment, and prevention. Clin Infect Dis. 2002;35(suppl 2):S210–S224.4. Clifford GM, Smith JS, Aguado T, Franceschi S. Comparison of HPV type distribution in high-grade cervical lesions and cervical cancer: A meta-analysis. Br J Cancer. 2003:89;101–105.5. Muñoz N, Bosch FX, de Sanjosé S, et al. Epidemiologic classification of human papillomavirus types associated with cervical cancer. N Engl J Med. 2003;348: 518–527.*High risk; **low risk1. Howley PM. In: Fields Virology. Philadelphia, Pa: Lippincott-Raven; 1996:2045– Schiffman M, Castle PE. Arch Pathol Lab Med. 2003;127:930– 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;348:518– Clifford GM, Smith JS, Aguado T, Franceschi S. Br J Cancer. 2003:89;101–105.
7Infectious Virus Particle of HPV1,2 1/Baker/p. 1449/Figure 3; p. 1453/col 2/¶ 22/Chen/p. 563/col 2/¶ 2Capsid proteins:L1L2Key PointHPV is a nonenveloped, double-stranded DNA virus; its shell is composed of L1 (major) and L2 (minor) proteins.BackgroundHPV is a nonenveloped, double-stranded DNA virus encapsulated with an icosahedral shell.1,2 The virion is made up of 2 late capsid proteins — major (L1) and minor (L2).1,3The virus shell consists of 72 pentamers, with each pentamer consisting of 5 molecules of L1 that stud the surface of the particle, and 1 molecule of L2 that sits in the conical hollow in the center of the rosette that faces inward.2,4Virus neutralizing antibodies made in response to natural infections recognize conformational epitopes of L1 on the outer surface of the intact virus particle.5References1. Shah KV. Papovaviruses. In: Rose NR, de Macario EC, Folds JD, Lane HC, Nakamura RM, eds. Manual of Clinical Laboratory Immunology. 5th ed. Washington, DC: ASM Press; 1997:655–660.2. Baker TS, Newcomb WW, Olson NH, Cowsert LM, Olson C, Brown JC. Structures of bovine and human papillomaviruses: Analysis by cryoelectron microscopy and three-dimensional image reconstruction. Biophys J. 1991;60:1445–1456.3. Kirnbauer R, Booy F, Cheng N, Lowy DR, Schiller JT. Papillomavirus L1 major capsid protein self-assembles into virus-like particles that are highly immunogenic. Proc Natl Acad Sci USA. 1992;89:12180–12184.4. Chen XS, Garcea RL, Goldberg I, Casini G, Harrison SC. Structure of small virus-like particles assembled from the L1 protein of human papillomavirus 16. Mol Cell. 2000;5:557–567.5. Stanley M. Immune responses to human papillomavirus. Vaccine. 2006;24(Suppl 1):S16–S22.1/Shah/p. 655/col 1/¶ 3Viral DNA2/Baker/p. 1448/col 1/¶ 23/Kirnbauer/p /col 1/¶ 3/p /col 2/¶ 1Viral exteriorViral interior4/Chen/p. 563/col 2/¶ 2/p. 557/col 1/¶21. Baker TS, et al. Biophys J. 1991;60:1445–1456.2. Chen XS, et al. Mol Cell. 2000;5:557–567.5/Stanley/p. 5/col 1/¶ 1
10Invasive Cervical Cancer Natural History of HPV Infection and Potential Progression to Cervical Cancer10–1 Year0–5 Years1–20 YearsInitial HPV InfectionContinuing InfectionCIN 2/3Invasive Cervical CancerCIN 1Key PointInfection with HPV will typically clear, but some infections with high-risk HPV types may ultimately lead to cervical cancer via a number of intermediate steps.BackgroundFollowing initial HPV infection, the course of progression to cervical cancer depends on the type of HPV. Low-risk HPV types (such as HPV 6 or 11) have a negligible risk of progressing but may persist.1 Overall, the majority of HPV infections spontaneously clear within the first 24 months.2 High-risk types (such as types HPV 16 and 18) are often associated with CIN 2 or higher lesions. The strong association of HPV 16 with CIN 2 or greater suggests that lesions caused by this infection evolve to CIN 2 without a prolonged period as CIN 1.1 Approximately 57% of low-grade lesions (CIN 1) will regress, 32% will persist, and 11% will progress. The risk of developing invasive cancer is estimated to be 1% in patients with CIN 1. Approximately 43% of CIN 2 lesions will regress, 35% will persist, 22% will progress to CIN 3, and 5% will progress to invasive cancer. The likelihood of CIN 3 regressing is about 32%, persistence is <56%, and rate of progression to invasive cancer is >12%.3 In studies of women with HPV infection who developed CIN 2 or 3, the initial abnormal smear was interpreted as CIN 2 or 3 in two thirds of cases,1,4 indicating that most CIN 3 lesions do not evolve from CIN 1.1 In a large, prospective study, mean times of progression from mild, moderate, or severe dysplasia to development of carcinoma in situ (CIS) were 58, 38, and 12 months, respectively.5In general, CIN occurs at least a decade earlier than invasive cancer, supporting a concept of the temporal evolution of cervical cancer.3 Based on a Markov model that approximated age-specific incidence of cervical cancer and HPV infection-associated events, the peak prevalence of low-grade squamous intraepithelial lesions (LSIL) is at 28 years of age, at 42 years of age for HSIL, and at 48 years of age for cervical cancer.6References1. Pinto AP, Crum CP. Natural history of cervical neoplasia: Defining progression and its consequence. Clin Obstet Gynecol. 2000;43:352–362.2. Ho GYF, Bierman R, Beardsley L, Chang CJ, Burk RD. Natural history of cervicovaginal papillomavirus infection in young women. N Engl J Med. 1998;338:423–428.3. Ostor AG. Natural history of cervical intraepithelial neoplasia: A critical review. Int J Gynecol Pathol. 1993;12:186–192.4. Koutsky LA, Holmes KK, Critchlow CW, Stevens CE, Paavonen J, et al. A cohort study of the risk of cervical intraepithelial neoplasia grade 2 or 3 in relation to papillomavirus infection. N Engl J Med. 1992;327:1272–1278.5. Richart RM, Barron BA. A follow-up study of patients with cervical dysplasia. Am J Obstet Gynecol. 1969;105:386–393.6. Myers ER, McCrory DC, Nanda K, Bastian L, Matchar DB. Mathematical model for the natural history of human papillomavirus infection and cervical carcinogenesis. Am J Epidemiol. 2000;151:1158–1171.Cleared HPV Infection1. Pinto AP, Crum CP. Clin Obstet Gynecol. 2000;43:352–362.
11HPV ClearanceIn women years of age ~80% of HPV infections are transientGradual development of cell-mediated immune response presumed mechanismIn a study of 608 college women, 443 infected, 70% of new infections cleared within 1 year and 91% within 2 yearsMean duration of infection - 8 monthsHPV 16 and 18 infections persist longerKey PointSeveral studies have confirmed that HPV 16 is more likely to persist than other HPV types.1BackgroundSeveral studies have evaluated the duration of HPV infection. In the study by Ho and colleagues, 608 college women in the United States were followed (mean age, 20 years) for an average of 2.2 years.2 The investigators reported median durations of infections of 11 months (95% CI, 7–12 months) and 12 months (95% CI, 6–17 months) with HPV types and 18, respectively. In contrast, the median duration of HPV 6 infection was 6 months (95% CI, 6–7 months).2In a study of 1610 Colombian women 15–85 years of age (median age, 32 years), the median duration of high-risk HPV infection was 15 months (95% CI, 13–17 months), whereas the median duration of low-risk HPV infection was 11 months (95% CI, 8–17 months). Duration of infection with HPV types 16 and 18 were 14 months (95% CI, 8–19 months) and 12 months (95% CI, 9–17 months), respectively.3Among university students 17–42 years of age (mean, 23 years) in Canada, Richardson and colleagues reported a slightly longer median time to loss of HPV infection in individuals infected with high-risk HPV types (17 months; 95% CI, 15–19 months) compared with individuals infected with low-risk HPV types (15 months; 95% CI, 11–18 months). Duration of infection for HPV types 16, 18, and 6 were 19 months (95% CI, 11–28 months), 9 months (95% CI, 5–14 months), and 6 months (95% CI, 5–8 months), respectively.4In a study of the duration of HPV infection in 1075 women 15–19 years of age (median, 18 years) in the United Kingdom, Woodman and colleagues reported median durations of detectability of 10 months (95% CI, 7–17) for HPV 16, 8 months (95% CI, 6–13) for HPV 18, and 9 months (95% CI, 6–13) for HPV type 6 or 11.5References1. Molano M, van den Brule A, Plummer M, et al. Determinants of clearance of human papillomavirus infections in Colombian women with normal cytology: A population-based, 5-year follow-up study. Am J Epidemiol. 2003;158:486–494.2. Ho GY, Bierman R, Beardsley L, Chang CJ, Burk RD. Natural history of cervicovaginal papillomavirus infection in young women. N Engl J Med. 1998;338:423–428.3. Muñoz N, Méndez F, Posso H, et al. Incidence, duration, and determinants of cervical human papillomavirus infection in a cohort of Colombian women with normal cytological results. J Infect Dis. 2004;190:2077–2087.4. Richardson H, Kelsall G, Tellier P, et al. The natural history of type-specific human papillomavirus infections in female university students. Cancer Epidemiol Biomarkers Prev. 2003;12:485–490.5. Woodman CB, Collins S, Winter H, et al. Natural history of cervical human papillomavirus infection in young women: A longitudinal cohort study. Lancet. 2001;357:1831–1836.
12Cervical Cancer Prevention Education About early symptom of cancer cervixAvoid Risk FactorsScreening and Vaccine
13Risk Co Factor: HIV HPV 16,18 SMOKING MULTIPPLE SEXUAL PARTNER ? BCP
14Cancer CervixHas an easily identified pre-invasive disease and be diagnosed and treated before become an invasive diseaseScreening Test
22Ideal (not essential) Patient’s Conditions For Screening No vagina douching for 48 hoursAvoided use of contraceptive creams or jellies for 48 hoursNo intercourse for 24 hoursNot recommended during menstruation, mid cycle smear is optimumPatient should be required to provide her LMP
36Cancer of the Cervix Histological types Squamous cell caAdenocarcinomaOther
37Cancer of the Cervix Mode of spread DirectLymphaticHematogenous
38Cancer of the Cervix Investigations EUAComplete blood countLiver function testRenal function testsCXR/IVP or CTCystoscopySigmoidoscopy
39Cancer of the Cervix FIGO Staging ( clinical ) I - Tumour confined to the cervixII- Upper 2/3 vagina / parametrium.III- Lower 1/3 vagina / pelvic side wall or hydronephrosisIV- Adjacent organ / Distant metastasis
52Gardasil: Quadrivalent HPV Vaccine 0.5 ml IM, day 0, month 2, and month 6COST ~$130 each vaccine doseStorage: 2-8oC, should not be frozen, protect from light. *NEED TO PRESERVE THE “COLD CHAIN”*Contraindications: hypersensitivity to the active substances or componentsPrecautions:May not be effectiveNot for use in active warts, cervical cancer, CIN VIN, VAINDoes not provide protection against none vaccine HPV typesNot recommended for use in pregnancy, Category B
53Who? Women 9-26 Do not need to have pap smear before vaccination Testing for HPV is not recommended prior to vaccinationSexually active women can be vaccinated, may be less effective in women who have been previously exposed to HPV
54Cervical Cancer DR KHALID H. WALI SAIT (FRCSC) 1920 colposcopy1930 was used in EuropeUSAACCSPSHORT FOCAL LENGTH CAN NOT DO BIOPSYLONG FOCAL LENGTH NOT COMFORTABLE PERFORM BIOPSY5 % UNSATSF COLPOSCOPYDR KHALID H. WALI SAIT (FRCSC)ASSOCIATE PROFESSOR OF GYNECOLOGICAL ONCOLOGYKing Abdulaziz University Hospital, Jeddah, Saudi Arabia