Diagnostics

a cytological screening test for cervical cancer in which a cell sample taken from the cervix is examined for cellular abnormalities that may be indicative of cervical cancer

A proper technique is essential for obtaining highly specific test results. [24]

• To obtain the specimen, use a sterile speculum to visualize the cervix

• Cleanse the cervix using a cotton pledget.

• Visualize the transformation zone and, if possible, the squamocolumnar junction.

• The specimen must be collected using a spatula or brush that is rotated by 360 degrees.

  • Scraping of ectocervix

  • Scraping of endocervix

• A thin layer of the specimen is uniformly applied to the labeled glass slide.

  • Immediate fixation

    • Using 95% ethyl alcohol (or spray fixative) to avoid drying

    • Hold the fixative spray 15–20 cm away from the slide and spray evenly.

  • Stain using Papanicolaou dye.

• Perform every 3 years if done alone

• Perform every 5 years as co-testing

• Findings: Pap smear results the Bethesda system (see below)

• Advantages: detects early cellular changes indicating a risk for the development of cervical cancer

• Contraindications

  • History of hysterectomy for nonmalignant disease

  • History of endometrial cancer

• Description: a screening test for cervical cancer in which cells collected from the cervix are tested for infection with high-risk HPV types

  • The viral DNA or RNA is detected using PCR-based assays.

  • Assays can detect HPV through:

    • Direct genome detection

    • Amplification of HPV fragments

    • Amplification and genotyping of HPV 16 and HPV 18

• Types

  • Primary HPV test (done without concurrent Pap smear)

    • Preferred cervical cancer screening test

    • Only certain FDA-approved HPV tests can be used for primary HPV testing (i.e., Cobas HPV test, Onclarity HPV assay, APTIMA HPV assay, Hybrid Capture 2).

  • Co-test (with concurrent Pap smear)

    • Used when primary HPV tests are not available

    • The sample obtained for the Pap smear can also be used for DNA testing.

  • Reflex HPV test (triage HPV test)

    • A test used to detect the DNA of high-risk HPV types

    • Performed after an abnormal Pap smear, typically using the same Pap smear sample showing abnormal cells

• Indications: screening for cervical intraepithelial neoplasia and invasive cervical cancer in individuals 25–65 years of age

• Screening interval: perform every 5 years with HPV primary test and co-test

• Findings (dependent on the primary HPV test used)

  • Pool detection of cancer-associated HPV subtypes (e.g., 16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 68)

  • Specific report of presence or absence of HPV subtypes (e.g., 16, 18)

a procedure using a colposcope to examine the cervix, vagina, vulva, and anus for precancerous lesions or abnormalities

• The procedure allows magnified visualization of the epithelium to guide biopsy sampling for histologic diagnosis.

• In case of referral due to previous abnormal cytology and HPV results, testing can be repeated during this procedure.

• Abnormal findings on gross cervical, vulvar, vaginal examination

• Abnormal results (past or current) of cervical screening test indicating a high risk for CIN III, adenocarcinoma in situ, or invasive cervical cancer

• ASC-H result in Pap smear

• Positive primary HPV tests for subtypes 16 or 18, if reflex HPV testing is not possible

• Two consecutive inconclusive cytology results in HPV-positive individuals > 25 years of age.

• Cervical leukoplakia: a collection of atypical cells that form a white membrane on the cervix that cannot be scraped off

  • May indicate hyperkeratosis, parakeratosis, or CIN

  • Leukoplakia can arise at or near the transformation zone

  • Biopsy required for further evaluation

• Acetowhite epithelium: an area of the cervical epithelium that appears white after the application of acetic acid [30]

  • Suggests atypical changes of the epithelium

  • Requires further evaluation with 2–4 targeted biopsies

• Findings suspicious for invasive cervical cancer include:

  • Gross exophytic or endophytic neoplasm

  • Ulceration

  • Necrosis

  • Erosions

  • Atypical growth of the vessels (e.g., corkscrew or comma-like shape)

identification and early treatment of precancerous or cancerous lesions

• Allows for closer visualization of cervical lesions (the squamocolumnar junction and all lesions must be completely visualized)

• Allows for identification of precancerous and cancerous lesions using acetic acid

• Allows for biopsy or excision of suspicious lesions

A cervical biopsy is usually done when abnormalities are found during a pelvic exam, Pap smear, and/or HPV test. It is often performed as part of a colposcopy.

• Punch biopsy

  • A small piece of cervical tissue (diameter < 5 mm) is removed by a circular blade.

  • More than one punch biopsies (2–4 targeted biopsies) may be performed on different areas of the cervix. [31]

  • Indication: acetowhite area seen during colposcopy

• Cone biopsy: See “Conization” below.

• Endocervical curettage (ECC) [32][33]

  • The mucous membrane of the endocervical canal is scraped by a curette.

  • Indications

    • Nonpregnant patients in whom colposcopy is inconclusive

    • Upper limit of the transformation zone cannot be visualized on colposcopy

    • Positive screening test (primary HPV test, Pap smear, co-testing) without visible lesion on the ectocervix

    • Visible HSIL or ASC-H

    • Suspicion of glandular abnormalities on cytology (e.g., adenocarcinoma)