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