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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
      • 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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Questions (2)
Lab Values
Blood, Plasma, Serum Reference Range
ALT 8-20 U/L
Amylase, serum 25-125 U/L
AST 8-20 U/L
Bilirubin, serum (adult) Total // Direct 0.1-1.0 mg/dL // 0.0-0.3 mg/dL
Calcium, serum (Ca2+) 8.4-10.2 mg/dL
Cholesterol, serum Rec: < 200 mg/dL
Cortisol, serum 0800 h: 5-23 μg/dL //1600 h:
3-15 μg/dL
2000 h: ≤ 50% of 0800 h
Creatine kinase, serum Male: 25-90 U/L
Female: 10-70 U/L
Creatinine, serum 0.6-1.2 mg/dL
Electrolytes, serum  
Sodium (Na+) 136-145 mEq/L
Chloride (Cl-) 95-105 mEq/L
Potassium (K+) 3.5-5.0 mEq/L
Bicarbonate (HCO3-) 22-28 mEq/L
Magnesium (Mg2+) 1.5-2.0 mEq/L
Estriol, total, serum (in pregnancy)  
24-28 wks // 32-36 wks 30-170 ng/mL // 60-280 ng/mL
28-32 wk // 36-40 wks 40-220 ng/mL // 80-350 ng/mL
Ferritin, serum Male: 15-200 ng/mL
Female: 12-150 ng/mL
Follicle-stimulating hormone, serum/plasma Male: 4-25 mIU/mL
Female: premenopause: 4-30 mIU/mL
midcycle peak: 10-90 mIU/mL
postmenopause: 40-250
pH 7.35-7.45
PCO2 33-45 mmHg
PO2 75-105 mmHg
Glucose, serum Fasting: 70-110 mg/dL
2-h postprandial:<120 mg/dL
Growth hormone - arginine stimulation Fasting: <5 ng/mL
Provocative stimuli: > 7ng/mL
Immunoglobulins, serum  
IgA 76-390 mg/dL
IgE 0-380 IU/mL
IgG 650-1500 mg/dL
IgM 40-345 mg/dL
Iron 50-170 μg/dL
Lactate dehydrogenase, serum 45-90 U/L
Luteinizing hormone, serum/plasma Male: 6-23 mIU/mL
Female: follicular phase: 5-30 mIU/mL
midcycle: 75-150 mIU/mL
postmenopause 30-200 mIU/mL
Osmolality, serum 275-295 mOsmol/kd H2O
Parathyroid hormone, serume, N-terminal 230-630 pg/mL
Phosphatase (alkaline), serum (p-NPP at 30° C) 20-70 U/L
Phosphorus (inorganic), serum 3.0-4.5 mg/dL
Prolactin, serum (hPRL) < 20 ng/mL
Proteins, serum  
Total (recumbent) 6.0-7.8 g/dL
Albumin 3.5-5.5 g/dL
Globulin 2.3-3.5 g/dL
Thyroid-stimulating hormone, serum or plasma .5-5.0 μU/mL
Thyroidal iodine (123I) uptake 8%-30% of administered dose/24h
Thyroxine (T4), serum 5-12 μg/dL
Triglycerides, serum 35-160 mg/dL
Triiodothyronine (T3), serum (RIA) 115-190 ng/dL
Triiodothyronine (T3) resin uptake 25%-35%
Urea nitrogen, serum 7-18 mg/dL
Uric acid, serum 3.0-8.2 mg/dL
Hematologic Reference Range
Bleeding time 2-7 minutes
Erythrocyte count Male: 4.3-5.9 million/mm3
Female: 3.5-5.5 million mm3
Erythrocyte sedimentation rate (Westergren) Male: 0-15 mm/h
Female: 0-20 mm/h
Hematocrit Male: 41%-53%
Female: 36%-46%
Hemoglobin A1c ≤ 6 %
Hemoglobin, blood Male: 13.5-17.5 g/dL
Female: 12.0-16.0 g/dL
Hemoglobin, plasma 1-4 mg/dL
Leukocyte count and differential  
Leukocyte count 4,500-11,000/mm3
Segmented neutrophils 54%-62%
Bands 3%-5%
Eosinophils 1%-3%
Basophils 0%-0.75%
Lymphocytes 25%-33%
Monocytes 3%-7%
Mean corpuscular hemoglobin 25.4-34.6 pg/cell
Mean corpuscular hemoglobin concentration 31%-36% Hb/cell
Mean corpuscular volume 80-100 μm3
Partial thromboplastin time (activated) 25-40 seconds
Platelet count 150,000-400,000/mm3
Prothrombin time 11-15 seconds
Reticulocyte count 0.5%-1.5% of red cells
Thrombin time < 2 seconds deviation from control
Volume  
Plasma Male: 25-43 mL/kg
Female: 28-45 mL/kg
Red cell Male: 20-36 mL/kg
Female: 19-31 mL/kg
Cerebrospinal Fluid Reference Range
Cell count 0-5/mm3
Chloride 118-132 mEq/L
Gamma globulin 3%-12% total proteins
Glucose 40-70 mg/dL
Pressure 70-180 mm H2O
Proteins, total < 40 mg/dL
Sweat Reference Range
Chloride 0-35 mmol/L
Urine  
Calcium 100-300 mg/24 h
Chloride Varies with intake
Creatinine clearance Male: 97-137 mL/min
Female: 88-128 mL/min
Estriol, total (in pregnancy)  
30 wks 6-18 mg/24 h
35 wks 9-28 mg/24 h
40 wks 13-42 mg/24 h
17-Hydroxycorticosteroids Male: 3.0-10.0 mg/24 h
Female: 2.0-8.0 mg/24 h
17-Ketosteroids, total Male: 8-20 mg/24 h
Female: 6-15 mg/24 h
Osmolality 50-1400 mOsmol/kg H2O
Oxalate 8-40 μg/mL
Potassium Varies with diet
Proteins, total < 150 mg/24 h
Sodium Varies with diet
Uric acid Varies with diet
Body Mass Index (BMI) Adult: 19-25 kg/m2
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