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Updated: Apr 2 2022

Cervical Cancer

  • Snapshot
    • A 50-year-old woman presents to her gynecologist due to abnormal vaginal bleeding. She notices bleeding after intercourse and in between her menstrual cycles. On pelvic examination, there is 3 cm exophytic mass originating in the cervix. Cervical biopsy demonstrates squamous cell carcinoma.
  • Introduction
    • Overview
      • cancer that typically arises from the transformation zone of the cervix
    • Epidemiology
      • incidence
        • 3rd most common cause of malignancy in women
          • first is endometrial and second is ovarian
        • average age of presentation is 45 years of age
      • risk factors
        • human papillomavirus (HPV) infection
          • double-stranded DNA oncovirus
          • especially HPV-16 and HPV-18
        • multiple sexual partners
        • current smoking
        • immunosuppression
    • Pathophysiology
      • HPV infects the immature basal layer of the cervical epithelium in areas of epithelial breaks, leading to basal cell replication through the synthesis of oncogenic proteins
        • E6 and E7
          • believed to be responsible for HPV's oncogenic properties
          • E6 inhibits p53, a tumor suppressor protein
          • E7 inhibits retinoblastoma protein (Rb), a tumor suppressor protein
      • persistent HPV leads to squamous intraepithelial lesions
        • graded as
          • atypical squamous cells of undetermined significance (ASC-US)
            • abnormal cells that are not adequate enough to label low-grade squamous intraepithelial lesion (LSIL)
          • low-grade squamous intraepithelial lesion (LSIL)
            • previously termed cervical intraepithelial neoplasia (CIN) 1
            • mild dysplasia
            • most cases regress spontaneously
              • a small number of cases progress to high-grade squamous intraepithelial lesions (HSIL)
          • atypical squamous cells, cannot rule out HSIL (ASC-H)
            • abnormal cells that likely consist of high-grade squamous intraepithelial lesions (HSIL)
          • high-grade squamous intraepithelial lesion (HSIL)
            • previously termed CIN 2 and CIN 3
            • moderate-to-severe dysplasia
            • carcinoma in situ
            • considered high risk for progressing to carcinoma
      • cervical carcinoma
        • squamous cell carcinoma is the most common (~80% of cases)
          • invades the underlying cervical stroma through the basement membrane
        • adenocarcinoma is the second most common (~15% of cases)
    • Associated conditions
      • HIV
      • HPV
    • Preventive
      • HPV vaccine
        • indication
          • females and males ages 11-12 years (routinely given) up to the 26 years of age
        • not recommended during pregnancy
  • Presentation
    • Symptoms
      • asymptomatic in early stages
      • vaginal bleeding
        • can be post-coital, intermenstrual, postmenopausal, or spontaneous
      • bladder outlet obstruction in advanced lesions
        • pelvic pain
        • hematuria
        • renal failure
    • Physical exam
      • pelvic exam
        • superficial ulceration
        • exophytic tumor in some cases
        • indurated cervix may be found
  • Studies
    • Invasive studies
      • pap smear
        • cells from the transformation zone of the cervix are collected and placed on a slide
          • determines if the cells are normal, ASC-US, LSIL, ASC-H, HSIL, or cervical cancer
        • indications
          • women between the ages of 21-65 every 3 years
          • women between the ages of 30-65 every 5 years with HPV testing
          • special circumstance
            • immunocompromised patients should be screen 1 year after the onset of sexual activity or by 21 years of age, which ever comes first
        • management
          • ASC-US
            • any age
              • repeat pap smear in 1 year
              • HPV DNA testing (preferred)
          • LSIL
            • 21-24 years of age
              • repeat pap smear in 1 year
            • ≥ 25 years of age
              • HPV DNA testing
          • ASC-H
            • any age
              • colposcopy with biopsy
          • HSIL
            • any age
              • colposcopy with biopsy
            • ≥ 25 years of age
              • immediate loop electrosurgical excision procedure (LEEP)
                • not if the patient is pregnant
          • cancer
            • imaging should be performed for clinical staging and risk assessment
      • colposcopy
        • allows for a magnified view of the cervix
          • helps identify precancerous and cancerous lesions with the use of acetic acid
        • indication
          • as a follow-up test in patients with abnormal pap smears, HPV testing, or gross abnormalities of the cervix, vagina, or vulva
            • can perform a directed cervical biopsy or excision with colposcopy
            • adequate colposcopy requires that the whole squamocolumnar junction and all lesions be completely visualized
      • cervical conization
        • indication
          • when cervical malignancy is suspected by cannot be determined with cervical biopsies
  • Differential
    • Cervicitis
      • differentiating factors
        • inflammation of the cervix, most commonly secondary to sexually transmitted infections (e.g., chlamydia and gonorrhea)
  • Treatment
    • Cervical cancer
      • treatment is based on the staging, nodal status, and pathology
        • e.g., ≤ 4 cm tumor confined to the cervix is managed with surgical resection or radiation
  • Complications
    • Lymphedema of the lower extremities
    • Sexual dysfunction
    • Metastasis
    • May invade rectum, bladder, ureters, and vagina
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