5. Cervical cancer for nurse student .pptx

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1. Cervical Cancer Abinet Abebe (B.Pharm, M.Sc. in Clinical Pharmacy) Department of Clinical Pharmacy and Pharmacy Practice School of Pharmacy, CHMS, Mizan Tepi University 3/3/2021 1

2. Contents Introduction Etiology Risk factors Pathophysiology Clinical presentation and diagnosis Treatment 3/3/2021 2

3. Introduction Cervical cancer is a malignant neoplasm arising from cells originating in the cervix uteri It is the third most common gynecologic cancer Average age at diagnosis is 45 years & cure with early treatment is >95%. 3/3/2021 3

4. Intro…….. Anatomy & transformation of the cervix Cervix is composed of columnar epithelium , which lines endocervical canal, & squamous epithelium , which covers the ectocervix. The point at w/c they meet is called squamocolumnar junction (SCJ) SCJ is a dynamic point that it changes in response to puberty, pregnancy, menopause, & hormonal stimulation. CIN is believed to originate as a single focus in the transformation zone at the advancing SCJ. 3/3/2021 4

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7. Epidemiology Globally, cervical cancer accounted for an estimated 528,000 new cancer cases worldwide and for 266,000 deaths in 2012 Global incidence and mortality rates depend upon the presence of screening programs for cervical precancer and cancer and of human papillomavirus (HPV) vaccination Cervical cancer is most common type of cancer and the third most common cause of cancer mortality in women in developing countries 3/3/2021 7

8. Risk Factors The two major histologic types of cervical cancer, adenocarcinoma and squamous cell carcinoma share many of the same risk factors . These include: Early onset of sexual activity Multiple sexual partners A high-risk sexual partner ( eg , a partner with multiple sexual partners ) History of sexually transmitted infections ( eg , Genital herpes) History of vulvar or vaginal cancer Long term OCP use Immunosuppression ( eg , human immunodeficiency virus infection ) 3/3/2021 8

9. Etiology and Pathophysiology Human papillomavirus (HPV) is central to the development of cervical neoplasia and detected in 99.7% of cervical cancers. M ajority of women infected with HPV not develop CIN or cervical ca. Other cofactors are important in development of CIN or cervical ca- such as cigarette smoking, immunosuppressant, contraceptive use, infection with other STDs & nutrition. 3/3/2021 9

10. There are four major steps in cervical cancer development: Oncogenic HPV infection of the metaplastic epithelium at the cervical transformation zone ( SCJ ) Persistence of the HPV infection Progression of a clone of epithelial cells from persistent viral infection to precancer Development of carcinoma and invasion through the basement membrane 3/3/2021 10

11. Cervical intraepithelial Neoplasia/CIN Preinvasive disease of the cervix Formerly called dysplasia: disordered growth & development of epithelial lining of cervix. Dysplasia =CIN Mild dysplasia (CIN 1) – disordered growth of one third of epithelial lining. Moderate dysplasia(CIN 2)-abnormal maturation of lower two third of lining Sever dysplasia ( CIN 3 ) – encompasses > two third of the epithelial thickness 3/3/2021 11

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13. Herpes simplex virus-2 infection as a cofactor in cervical cancer pathogenesis has been reported in some patients The distribution of histopathologic types of cervical cancer are Squamous cell carcinoma – 69 % Adenocarcinoma (including adenosquamous) – 25 % Other histologies – 6 % 3/3/2021 13

14. Cervical cancer can spread by direct extension or by lymphatic or hematogenous dissemination. Direct extension may involve the uterine corpus, vagina, parametria, peritoneal cavity, bladder, or rectum. The most common sites for hematogenous spread are the lungs, liver, and bone ; where as the bowel, adrenal glands, spleen, and brain are less frequent sites 3/3/2021 14

15. Screening Screening aims to detect precancerous changes , which if not treated may lead to cancer Screening techniques Cytology screening Visual inspection HPV testing 3/3/2021 15

16. Prevention Gardasil and Cervarix Are prophylactic vaccines for the primary prevention of HPV types 16 and 18 (implicated in 70% of cervical cancers) A three dose intramuscular administration at 0, 1–2 and 6 months is required Initial recommendations for use included: 9–13 year old females prior to coitarche and 14–26 year old females, even if already sexually active , with a history of cervical abnormalities or prior HPV exposure. The vaccine not recommended for pregnant females or less than 9 years of age. For women older than 26 years, immunization could be considered 3/3/2021 16

17. CLINICAL MANIFESTATIONS Early cervical cancer is frequently asymptomatic , most common symptoms at presentation are: Irregular or heavy vaginal bleeding Postcoital bleeding Some women present with a vaginal discharge that may be watery, mucoid, or purulent and malodorous, this is a nonspecific finding and may be mistaken for vaginitis or cervicitis . 3/3/2021 17

18. Advanced disease may present with pelvic or lower back pain, which may radiate along the posterior side of the lower extremities. Bowel or urinary symptoms, such as pressure-related complaints, hematuria, hematochezia are uncommon and suggest advanced disease. In asymptomatic women, cervical cancer may be discovered as a result of cervical cancer screening or incidentally, if a visible lesion is discovered upon pelvic examination 3/3/2021 18

19. Symptoms/Signs Usually asymptomatic AUB ( menorrhagia, postcoital bleeding, or postmenopausal bleeding) Profuse and often malodorus discharge Low back pain Obstructive uropathy Lymphadenopathy Weight loss Anemia 3/3/2021 19

20. Diagnosis H istologic evaluation of a cervical biopsy Physical examination A pelvic examination :any woman with symptoms suggestive of cervical cancer Any lesion that is raised, friable should be biopsied R ectovaginal examination with assessment of tumor size and vaginal or parametrial involvement is required for staging Other findings : palpable groin , supraclavicular lymph nodes. 3/3/2021 20

21. Cervical cytology  Principal method for cervical cancer screening. Performed for women with suspected cervical cancer Cervical biopsy and colposcopy Cervical conization 3/3/2021 21

22. FIGO Clinical Staging of Cervical ca Stage 0 - Carcinoma in situ Stage I : Cervical carcinoma confined to the cervix/ uterine corpus    Stage IA - Invasive cervical cancer diagnosed by microscopy only      Stage IA1- Stromal invasion no deeper than 3 mm, no wider than 7 mm     Stage IA2- Stromal invasion greater than 3, but less than 5 mm and no wider than 7 mm in horizontal spread    3/3/2021 22

23. Stage IB : Clinically visible lesion confined to the cervix or microscopic disease greater than stage IA      Stage IB1 : Lesion not greater than 4 cm      Stage IB2: Lesion greater than 4 cm 3/3/2021 23

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25. Stage II- Tumor extends beyond uterus but not to pelvic sidewall or lower third of vagina    Stage IIA :Vaginal involvement without parametrial involvement    Stage IIB : Parametrial involvement 3/3/2021 25

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27. Stage III-Tumor extends to pelvic sidewall and/or causes hydronephrosis and/or extends to lower third of vagina    Stage IIIA: Involvement of lower third of vagina    Stage IIIB : Extension to pelvic sidewall and/or hydronephrosis 3/3/2021 27

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29. Stage IV-Extension beyond the true pelvis or into mucosa of rectum or bladder    Stage IVA - Extension into adjacent organs    Stage IVB- Distant metastases 3/3/2021 29

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31. Five Year Survival of Cervix Cancer by Stage of Disease 3/3/2021 31

32. Treatment of Cervical Cancer Management of early-stage cervical cancer Early-stage cervical cancer refers to FIGO stage IA or IB1 disease Treatment options for these women include M odified radical hysterectomy, F ertility-sparing surgery, or P rimary radiation therapy (RT) with or without chemotherapy. The choice of therapy depends on tumor and patient factors 3/3/2021 32

33. For women with early-stage cervical cancer, a modified radical hysterectomy is suggested than radiation therapy (RT) Modified radical hysterectomy includes removal of the uterus, cervix, upper one-fourth of the vagina, and parametria . 3/3/2021 33

34. For some patients, an alternative to modified radical hysterectomy is reasonable . These are women with/at M icroscopic disease (stage IA1) with no evidence of high-risk features may treated with cone biopsy or extrafascial hysterectomy R eproductive age with early-stage disease who wish to preserve fertility Who are not surgical candidates; should receive primary RT. 3/3/2021 34

35. For women with high-risk factors ( ie , pathologically involved lymph nodes, parametrial invasion, or positive surgical margins), chemoradiation is recommended rather than observation or adjuvant RT alone. For women with high-risk factors, the recurrence risk is 40 % and risk of death is up to 50 % following surgery alone Chemoradiation is associated with an improvement in both PFS and OS 3/3/2021 35

36. For chemoradiation in high-risk, early-stage cervical cancer, F our cycles of cisplatin 70 mg/m2 on day 1, plus FU 1000 mg/m2 per day for four days, every three weeks is given in combination with RT. Single-agent weekly cisplatin (40 mg/m2) during RT is recommended. Because, single-agent cisplatin administered with RT achieves similar outcomes to cisplatin plus FU and has a better toxicity profile and associated with less morbidity than cisplatin plus FU. 3/3/2021 36

37. Management of locally advanced cervical cancer L ocally advanced cervical cancer (stage IB2 to IVA) have a higher rate of recurrence and worse survival than early-stage disease After surgery alone, the rate of relapse is at least 30% Primary Chemoradiation P rimary chemoradiation is suggested, although the benefits of treatment are greater with earlier (stage IB2 to IIB) versus more advanced stage (stage III to IVA) 3/3/2021 37

38. The benefit of chemoradiation for women with locally advanced cervical cancer rather than RT alone: chemoradiation A reduction in the risk of death A reduction in the risk of recurrence and A reduction in distant metastases But, there is higher rates of serious (grade 3/4) adverse events, including gastrointestinal toxicity 3/3/2021 38

39. Chemotherapy regimen Chemotherapy, either single-agent cisplatin or cisplatin plus fluorouracil (FU) for treatment of cervical cancer Single-agent cisplatin with RT achieves similar outcomes to cisplatin plus FU and has a better toxicity profile, treatment with cisplatin resulted in: H igher rate of completion of chemoradiation, Less serious (grade 3/4) hematologic toxicity and Similar complete response rate and overall survival rate 3/3/2021 39

40. Patients with potential contraindications to cisplatin Cisplatin is associated with significant toxicities, including risks of long-standing neuropathy and potentially chronic renal insufficiency P atients with chronic or persistent comorbidities ( eg , patients with chronic renal failure or severe baseline neuropathy) face a greater risk of experiencing these complications. It is prefer able to treat these patients with weekly carboplatin (100 mg/m2) concurrently with RT Weekly gemcitabine (300 mg/m2) is an option 3/3/2021 40

41. Radiation therapy For most women, RT (in conjunction with chemotherapy) is delivered to the pelvis using external-beam RT . Cervical brachytherapy is also administered to maximize local control Brachytherapy is the local application of radiation to cervix/vagina. It is an essential component of treatment for locally advanced cervical cancer and allows for a higher dose of RT to the cervix while sparing the surrounding normal tissue 3/3/2021 41

42. Importance of time to completion of chemoradiation For all women undergoing chemoradiation, treatment should be completed within eight weeks . Studies showed ; Time to completion of brachytherapy >56 days was associated with a higher rate of disease progression within the pelvis Treatment duration > 62 days may impact disease-free survival 3/3/2021 42

43. P oor candidates for primary chemoradiation include: Women with acute or chronic pelvic inflammatory disease Women with a coexistent pelvic mass ( dual malignancy) Women with anatomic alterations that make optimal RT difficult Women in whom compliance with RT would be difficult Primary modified radical hysterectomy is reasonable in these patients 3/3/2021 43

44. Stage IVB : Persistent and recurrent disease For women who present with a local relapse confined to the cervix or vagina, treatment directed to the site of recurrence can be performed with curative intent Options include hysterectomy in patients who have received prior radiation, or radiation therapy (RT) in those who have not received radiation or are not surgical candidates Patients who have previously been treated with RT and those who are not candidates for surgical resection should be offered chemotherapy . 3/3/2021 44

45. For the majority of patients with metastatic disease and those who are not candidates for a local treatment approach, administer chemotherapy . For women being treated in the first-line setting , administer chemotherapy plus bevacizumab rather than chemotherapy alone. Treatment incorporating bevacizumab was shown to improve overall survival in these patients For patients with metastatic, advanced, or recurrent cervical cancer who are candidates for chemotherapy, cisplatin is the most widely used agent 3/3/2021 45

46. Chemotherapy plus bevacizumab as first-line treatment For women with recurrent, metastatic, or advanced cervical cancer, treatment consisting of a platinum-based combination plus the angiogenesis inhibitor, bevacizumab. Chemotherapy plus bevacizumab resulted in: A significant improvement in OS compared with chemotherapy alone A significant improvement in PFS But treatment with bevacizumab resulted in a significantly increased rate of hypertension, defined as systolic BP 160/100 mmHg and above . Other serious (grade 3/4) toxicities included: gastrointestinal fistula; genitourinary fistula; neutropenia and thrombosis or embolism 3/3/2021 46

47. Combination chemotherapy In the first-line setting , a platinum-based combination is suggested, regardless of whether bevacizumab is administered. In addition, a platinum-based combination is supported rather than single-agent cisplatin. Preferred combination is cisplatin plus paclitaxel rather than other cisplatin-based regimens Cisplatin plus gemcitabine resulted in much less serious febrile neutropenia compared with cisplatin in combination with paclitaxel or topotecan, however, cisplatin plus paclitaxel resulted in less serious thrombocytopenia 3/3/2021 47

48. Alternate use of carboplatin Because of the toxicity seen with cisplatin-based combination chemotherapy, carboplatin is a reasonable substitute for cisplatin , particularly for patients with medical comorbidities , previously treated with cisplatin-based chemoradiation Second-line therapy For women who have progressed after first-line treatment and those patients who are not candidates for combination chemotherapy, single-agent second line chemotherapy is recommended. 3/3/2021 48

49. A choice among active agents must be tailored to the individual patient, with consideration to prior therapies received and residual toxicity The most active single agents are: Carboplatin Paclitaxel (175 mg/m2 IV every three weeks Ifosfamide (1.2 g/m2 IV daily for five days every 28 days) Topotecan (1.5 mg/m2 IV daily for five days every 21 days) Irinotecan (125 mg/m2 IV every three weeks) 3/3/2021 49

50. Cervical Cancer Treatment Regimens Chemoradiation as Primary Therapy, Adjuvant Therapy, or Therapy for Recurrent Disease 3/3/2021 50

51. Systemic Therapy for Recurrent or Metastatic Disease 3/3/2021 51

52. Systemic Therapy for Recurrent or Metastatic Disease 3/3/2021 52

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55. Cisplatin, Carboplatin, Docetaxel, and Paclitaxel may cause drug reaction …….. Hydration is required with supplemental electrolytes pre- and post-administration of Cisplatin Hydration is required pre- and post-administration of Ifosfamide. 3/3/2021 55

56. Thank you! 3/3/2021 56