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