Review Topic
  • 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. 
  • 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
  • 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
  • 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
  • Cervicitis
    • differentiating factors
      • inflammation of the cervix, most commonly secondary to sexually transmitted infections (e.g., chlamydia and gonorrhea)
  • 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
  • Lymphedema of the lower extremities
  • Sexual dysfunction
  • Metastasis
  • May invade rectum, bladder, ureters, and vagina

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