Cervical Cancer: Test and Diagnosis

Cancer screening measures (KFEM)/cervical cancer screening

Asymptomatic women at average risk for cervical cancer should have the following screenings:

  • Cervical cancer screening:By law, cytologic smear tests (Pap tests) should be performed once a year beginning at age 20; from 2018 onward, women should be tested as part of the cancer screening measures (KFEM) as follows.Cervical cancer screening should occur as follows:
    • ≥ 20 years of age: annual palpation examination.
    • 20 – 34 years of age: annual Pap smear (cytological examination according to Papanicolaou; cervical smear/cell smear from the cervix).
    • ≥ 35 years of age: every 3 years combination examination:
      • Test for genital infections with human papillomavirus (HPV).
      • Pap smear
  • Abnormal Pap tests (IIw, III, IIID) are clarified using triage by cytology or colposcopy. If abnormal cytology findings are detected in women aged 30-34 years, HPV testing is performed as a clarification or triage test or colposcopy:
    • HPV test: molecular detection of HPV DNA (differentiation between low-risk and high-risk HPV infection); in women with a positive HPV detection, further clarification by cytology is currently recommendedNote: A 5-year screening interval with HPV testing in women older than 30 years promises more safety than a 3-year interval with cytology. Note: A negative HPV test excludes a CIN 3+ (CIN 3= carcinoma in situ) safer and longer than an inconspicuous cytology.
    • The following tests are available to estimate oncogenic activity (“cancer activity”):
      • Biomarkers:
        • P16 ( tumor suppressor protein; indirect marker of HPV oncogene activity).
        • Ki 67 (proliferation marker). HPV infection induces increased proliferation in cell nuclei, which is visualized by color immunocytochemistry

        Note: Only the simultaneous detection of both biomarkers in a cell is indicative of oncogenic transformation (“malignant transformation”), of the cervical cell by a persistent high-risk HPV infection and the indication for further clarification by differential colposcopy (cervical endoscopy) and sample excision (removal of a tissue sample for diagnostic purposes)In HPV-positive women, the risk for the development of cervical cancer precursors can be better estimated by the two biomarkers p16 and Ki 67:

        • Among women with a positive Pap test, the five-year cumulative risk of cervical cancer precursors (≥ CIN2) is significantly higher with dual staining, at 31% versus 25%.
        • In women with negative p16/Ki-67 test compared to an inconspicuous Pap test result, the cervical cancer precursor risk is significantly lower at 8.5% versus 12.3%.

        CONCLUSION: It is likely that the screening interval could be extended to three years in HPV-positive women with a negative biomarker test.

      • HPV L1 capsid protein detection: immunocytochemical detection in smear preparation.
        • Detection is an indication that the immune system can successfully fight the diseased cells.
        • If the L1 capsid protein is not detectable, progression (progression) of the infection toward cervical cancer must be expected
    • Differential colposcopy with biopsy (tissue sample) for histological clarification (fine tissue examination) as an immediate follow-up step after diagnosis of high-risk HPV infection without the intermediate steps: Biomarker or L1 capsid protein.

Further notes

  • Preliminary results from the open-label COMPASS (Cytology and Primary HPV Screening in Australia) study show that with a CIN2+ detection rate of 1.0% versus 0.1%, HPV testing was significantly superior to Pap screening.
  • The U.S. Preventive Services Task Force (USPSTF) considers DNA detection of oncogenic viruses (HPV testing) in women 30 years of age and older to be the better screening method: for the first time, it recommends that women aged 30 to 65 years have HPV testing every 5 years without Pap testing.
  • Not all cervical cancers are caused by HPV. In 8 of 178 primary tumors examined, a genomic analysis of the tumor found no evidence of infection with HPV and its oncogenes such as E6 and E7 (= HPV-negative carcinomas).Seven of the eight carcinomas showed great similarity to endometrial carcinoma (cancer of the uterus), meaning they also differ in other genes.

Diagnostic procedure for abnormal recurrent cytology.

Pap IIID/IVA: colposcopy (cervical endoscopy) → biopsy (tissue sampling):

  • CIN I → control
  • CIN II/III → surgical removal (see surgery: preinvasive lesions).

Pap IV B: colposcopy → biopsy

  • CIN III → surgery (see d.)
  • Invasive carcinoma → surgery (.s. d.)

Note: In the presence of cervical dysplasia with high-risk HPV, an anal Pap test is also abnormal in one in three women.

Laboratory diagnostics in cervical cancer

2nd-order laboratory parameters-depending on the results of the history, physical examination, etc.-for differential diagnostic workup

* 80% of cervical carcinomas are squamous cell carcinomas!