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cervical cancer

Also see Pap smear Etiology: Risk factors: 1) infection with human papillomavirus types 16*, 18*, 31, 33, 35, 45, 51, 52, 56 2) early age of 1st sexual intercourse 3) multiple sexual partners 4) male partner in a high risk group 5) low socioeconomic status 6) smoking 7) parity (number of pregnancies) [5] 8) oral contraceptive use [5]; risk declines with cessation, returns to baseline in 10 years [9] 9) HIV1 infection, including women taking antiretroviral therapy [31] * 50% associated with HPV-16 [6], 70% with types 16 or 18 Protective factors: 1) barrier methods of contraception 2) use of spermicides Epidemiology: 1) 3rd most common form of gynecologic cancer 2) 2nd most common cause of death from gynecologic cancer 3) annual incidence increases after age 35 50% of cases occur in women age 35-55 years 4) 57% of invasive cervical cancer occur in women > 50 years of age [8] 5) 25% of cases & 40% of deaths occur in women > 65 years of age 6) carcinoma in situ shows bimodal distribution a) 20-30 years of age b) 60-70 years of age 7) cervical cancer in women > 65 years of age may be underestimated due to prevalence of hysterectomy in elderly women [15] (23% of black women & 21% of white women) [22] 9) excluding women with hysterectomy, cervical cancer mortality among black women is 10.1 per 100,000 & 4.7 per 100,000 for white women [22] Pathology: - squamous cell carcinoma - most cervical cancers begin in the squamous cells of the transformation zone - metastases a) bone (21%) b) brain (9%) c) skin (3%) d) adrenal (31%) e) kidney (26%) Genetics: - associated with defects in FGFR3 - coexpression of KRT16 & KRT17 - other implicated genes NANOGP8, IGF2BP3, HES2, WAPAL, LETMD1, GUSB, PHF19, c-MYC, ST20, TP63, SLC39A6 Clinical manifestations: - early cervical cancer is frquently asymptomatic [2] - post-coital bleeding & other vaginal bleeding between menstrual periods - postmenopausal vaginal bleeding - ulcerative lesion arising from the transformation zone of the cervix (pelvic exam) - exophytic lesion arising from the transformation zone of the cervix - abnormal vaginal discharge, pelvic pain, low back pain, bowel & bladder dysfunction are symptoms of advanced cervical cancer [2] Laboratory: 1) HPV DNA 2) Pap smear - punch biopsy of obvious lesions (see below) 3) see ARUP consult [10] Special laboratory: 1) cervical biopsy - diagnosis of cervical cancer is made by cervical biopsy [31] - coloposcopy with cervical biopsy for tissue diagnosis 2) cystoscopy to examine bladder for local metastasis 3) proctoscopy to examine sigmoid colon for local metastasis Radiology: - PET/CT positron-emission tomography/computed tomography for staging - surveillance imaging for cervical cancer survivors only if signs or symptoms of recurrence [2] Complications: - recurrence of gynecologic cancer most often detected by symptoms or physical examination [1] - transmission of cancer to fetus during vaginal delivery [29] - 2 cases, both cases, infants developed lung cancer, - same type of malignancy as mother, 23 months & 6 years later - aspiration of meconium during vaginal delivery thought to be mechanism Staging: 0) stage 0: carcinoma in situ 1) stage 1: confined to uterus 2) stage 2: invades beyond uterus, but not to pelvic wall 3) stage 3: extend to pelvic wall &/or lower 3rd of vagina, or hydronephrosis 4) stage 4: invades mucosa of bladder or rectum or extends beyond pelvis Management: 1) stage 1A1 microscopic cancer in fertile younger women a) loop electrical excision procedure (LEEP) b) cervical cold-knife conization c) observation [2] d) preservation of fertility 2) total hysterectomy for carcinoma in situ & early invasive carcinoma (stage 1 or non-bulky stage 2A) - prophylaxis for venous thromboembolism for 5 weeks after hysterectomy [2,11] - ovarian conservation associated with favorable prognosis [21] - estrogen replacement therapy if radical hysterectomy [21] - sentinel lymph node biopsy vs para-aortic lymph node dissection up to inferior mesenteric artery if negative imaging [24] - laparoscopic or robot-assisted radical hysterectomy associated with lower survival than open surgery [25] 3) radiation therapy for more advanced disease, stages 1 & 2 - intensity-modulated radiotherapy [24] - more conformal dose distribution maximizes sparing of organs at risk [24] - 45-50 Gy (1.8 Gy per fraction) - should not exceed 5-6 weeks 4) chemotherapy with concurrent radiation therapy for stage 2, 3 & 4 [2] a) cisplatin + paclitaxel for stages 2-4 [2] b) topotecan for recurrent & stage IVB cervical cancer in combination with cisplatin ONLY if patient has NOT previously received cisplatin (NGC NICE) c) bevacizumab in combination with cisplatin + paclitaxel may improve survival in advanced cervical cancer [14] d) chemotherapy with concurrent radiation therapy improves survival over either alone e) hysterectomy is not done for stage 3 [2] 5) follow-up - pelvic examination & Pap smear every 3-6 months for 2 years, then every 6 months for the next 3 years, then annually - annual cervical or vaginal cytology (MKSAP19) [2] - more advanced disease, stages 1 & 2 may require periodic chest X-rays, CT of the abdomen & pelvis or both (may be outdated recommendation) [2] - additional imaging & laboratory testing only if signs of recurrence [2] 7) prognosis: 5 year survival by stage at presentation 0) stage 0: 100% 1) stage 1: 85% 2) stage 2: 60% 3) stage 3: 33% 4) stage 4: 7% 8) storing of embryos is an option prior to therapy in women of reproductive age 9) see screening for cervical cancer

Related

cervical intraepithelial neoplasia (CIN) papillomavirus screening for cervical cancer ulcerative lesion arising from the transformation zone of the cervix

General

cervical neoplasm urogenital malignancy (urogenital cancer)

Database Correlations

OMIM 603956

References

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  14. Tewari KS et al. Improved survival with bevacizumab in advanced cervical cancer. N Engl J Med 2014 Feb 20; 370:734 PMID: 24552320 http://www.nejm.org/doi/full/10.1056/NEJMoa1309748
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  32. National Cancer Institute Cervical Cancer - Helath Professional version https://www.cancer.gov/types/cervical/hp