cervical cancer

Introduction

Also see Pap smear

Etiology

Risk factors:

• infection with human papillomavirus types 16*, 18*, 31, 33, 35, 45, 51, 52, 56
• early age of 1st sexual intercourse
• multiple sexual partners
• male partner in a high risk group
• low socioeconomic status
• smoking
• parity (number of pregnancies)
• oral contraceptive use; risk declines with cessation, returns to baseline in 10 years
• HIV1 infection, including women taking antiretroviral therapy

* 50% associated with HPV-16, 70% with types 16 or 18

Protective factors:

• barrier methods of contraception
• use of spermicides

Epidemiology

• 3rd most common form of gynecologic cancer
• 2nd most common cause of death from gynecologic cancer
• annual incidence increases after age 35 50% of cases occur in women age 35-55 years
• 57% of invasive cervical cancer occur in women > 50 years of age
• 25% of cases & 40% of deaths occur in women > 65 years of age
• carcinoma in situ shows bimodal distribution
  • 20-30 years of age
  • 60-70 years of age
• cervical cancer in women > 65 years of age may be underestimated due to prevalence of hysterectomy in elderly women (23% of black women & 21% of white women)
• excluding women with hysterectomy, cervical cancer mortality among black women is 10.1 per 100,000 & 4.7 per 100,000 for white women

Pathology

• squamous cell carcinoma
  • most cervical cancers begin in the squamous cells of the transformation zone
• metastases
  • bone (21%)
  • brain (9%)
  • skin (3%)
  • adrenal (31%)
  • 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
• 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

Laboratory

• HPV DNA
• Pap smear
  • punch biopsy of obvious lesions (see below)
• see ARUP consult

Diagnostic procedures

• cervical biopsy
  • diagnosis of cervical cancer is made by cervical biopsy
  • coloposcopy with cervical biopsy for tissue diagnosis
• cystoscopy to examine bladder for local metastasis
• 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

Staging

0) stage 0: carcinoma in situ

• stage 1: confined to uterus
• stage 2: invades beyond uterus, but not to pelvic wall
• stage 3: extend to pelvic wall &/or lower 3rd of vagina, or hydronephrosis
• stage 4: invades mucosa of bladder or rectum or extends beyond pelvis

Complications

• recurrence of gynecologic cancer most often detected by symptoms or physical examination
• transmission of cancer to fetus during vaginal delivery
  • 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

Management

• stage 1A1 microscopic cancer in fertile younger women
  • loop electrical excision procedure (LEEP)
  • cervical cold-knife conization
  • observation
  • preservation of fertility
• 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
  • ovarian conservation associated with favorable prognosis
  • estrogen replacement therapy if radical hysterectomy
  • sentinel lymph node biopsy vs para-aortic lymph node dissection up to inferior mesenteric artery if negative imaging
  • laparoscopic or robot-assisted radical hysterectomy associated with lower survival than open surgery
• radiation therapy for more advanced disease, stages 1 & 2
  • intensity-modulated radiotherapy
    • more conformal dose distribution maximizes sparing of organs at risk
  • 45-50 Gy (1.8 Gy per fraction)
  • should not exceed 5-6 weeks
• chemotherapy with concurrent radiation therapy for stage 2, 3 & 4
  • cisplatin + paclitaxel for stages 2-4
  • topotecan for recurrent & stage IVB cervical cancer in combination with cisplatin ONLY if patient has NOT previously received cisplatin (NGC NICE)
  • bevacizumab in combination with cisplatin + paclitaxel may improve survival in advanced cervical cancer
  • chemotherapy with concurrent radiation therapy improves survival over either alone
  • hysterectomy is not done for stage 3
• 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)
  • more advanced disease, stages 1 & 2 may require periodic chest X-rays, CT of the abdomen & pelvis or both (may be outdated recommendation)
    • additional imaging & laboratory testing only if signs of recurrence
• prognosis: 5 year survival by stage at presentation 0) stage 0: 100%
• stage 1: 85%
• stage 2: 60%
• stage 3: 33%
• stage 4: 7%
• storing of embryos is an option prior to therapy in women of reproductive age
• see screening for cervical cancer

More general terms

• cervical neoplasm
• urogenital malignancy (urogenital cancer)

Additional terms

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

Patient information

cervical cancer patient information

Database

• OMIM: https://mirror.omim.org/entry/603956