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Evidence - Anesthesia examination, Pap smear, LEEP conization, cystoscopy, hysteroscopy, fractional curettage, rectoscopy

  1. Introduction

    Cervical cancer is one of the most common malignant diseases in women worldwide. The main cause is a persistent infection with high-risk HPV. The incidence of invasive carcinomas has been significantly reduced in recent decades through the cytological early detection program (Pap smear). Nevertheless, especially in cases of inadequate screening, advanced stages also occur. Guideline-compliant diagnostics and therapy are based on the tumor stage (FIGO classification) and individual risk factors.

    Reference:

    1. Guideline Program Oncology (German Cancer Society, German Cancer Aid, AWMF): S3 Guideline Diagnostics, Therapy and Follow-up Care of Patients with Cervical Cancer, Long Version, 2.2, 2022, AWMF Register Number: 032/033OL
    2. Fehm T, Beckmann MW, Mahner S, Denschlag D, Brucker S, Hillemanns P, Tempfer C; Uterus Commission of the AGO and the AGO Working Group. Statement of the Uterus Commission of the Gynecological Oncology Working Group (AGO) on Surgical Therapy for Patients with Stage IA2-IIB1 Cervical Cancer. Geburtshilfe Frauenheilkd. 2023 Oct 5;83(10):1199-1204. doi: 10.1055/a-2160-3279. PMID: 37808259; PMCID: PMC10556864.
  2. Important diagnostic procedures and their indication

    Clinical Examination and Anesthesia Examination: In cases of suspected cervical carcinoma, a gynecological examination with a speculum and palpation is initially performed. An examination under anesthesia can be useful to more accurately assess tumor size, parametrial involvement, and vaginal extension with relaxed muscles. It is mainly used for advanced findings or for preoperative staging. Nowadays, anesthesia examinations are applied selectively; modern imaging (e.g., MRI) has replaced many older staging examinations.

    Cytological Smear (Pap Test): The Pap smear is a central component of early detection. If an abnormal finding is present (e.g., Pap IIID, IVa, or higher), further diagnostics are initiated for clarification. However, a Pap smear alone does not provide a definitive diagnosis – abnormal cytology must be confirmed by histological examination. Nevertheless, the Pap test provides initial indications of dysplasia or carcinoma of the cervix.

    Colposcopy and Biopsy: Following an abnormal Pap finding, a colposcopy is performed. Under magnification and application of acetic acid, suspicious areas on the cervix can be identified. A biopsy is taken from abnormal areas to obtain a histological diagnosis. If a high-grade intraepithelial lesion or suspicion of invasion is confirmed, a conization is indicated.

    Diagnostic Conization (LEEP Conization): Conization – usually performed as Loop Excision (LEEP/LLETZ) or cold knife surgery – serves to completely remove the transformation zone of the cervix. It is diagnostic and, in very early carcinomas, simultaneously therapeutic. Indication: in cases of suspected microcarcinoma (e.g., HISTO PAP V/a, carcinoma in situ with suspicion of invasion) or non-definitive biopsy. Conization provides the definitive histological assessment: If invasive carcinoma is present, the specimen can be used to evaluate tumor size, depth of stromal invasion, and resection margin status (R0 vs. R1). A tumor removed with clear margins (R0 conization) can already be curative in microinvasive carcinomas (FIGO IA1). Otherwise, conization allows for precise staging and planning of definitive therapy.

    Fractional Curettage and Hysteroscopy: In cases of unclear genesis of a cervical adenocarcinoma or suspicion of a descending endometrial carcinoma with cervical involvement, fractional curettage is indicated. The mucosa of the cervical canal and uterine corpus is scraped separately and examined histologically. This allows differentiation of whether the tumor originates primarily from the cervix or if an endometrial carcinoma is present that has grown into the cervix. If necessary, a hysteroscopy with targeted biopsy is performed additionally. These measures are particularly important in postmenopausal bleeding to rule out endometrial carcinoma. Fractional curettage provides the basis for further therapy planning: An endometrial carcinoma with cervical involvement is treated according to stage like a corpus carcinoma (FIGO stage II) (usually primarily surgically with hysterectomy and adnexectomy), while a primary cervical carcinoma requires different therapeutic approaches.

    Imaging Procedures: Imaging examinations are used for pretherapeutic staging diagnostics. A transvaginal ultrasound can estimate tumor extension in the cervical area and, for example, detect hydronephrosis (indicating ureteral compression in advanced tumors). For tumors from approximately FIGO IB2 (≥4 cm), a pelvic MRI is generally recommended to assess local tumor extension (parametrial, vaginal involvement). For metastatic spread diagnostics, CT thorax/abdomen or PET-CT is used, especially in clinically advanced disease. Since the FIGO classification 2018, imaging is also included in staging, but it does not replace classical clinical findings.

    Cystoscopy and Rectoscopy: A bladder endoscopy (cystoscopy) or endoscopy of the rectum/sigmoid (recto- or rectosigmoidoscopy) is only indicated if there is a concrete suspicion of involvement of these organs. In extensive cervical carcinoma with possible infiltration of the bladder (e.g., in hematuria or anterior parametrial involvement), a cystoscopy can be performed to detect tumor infiltration of the bladder mucosa, which corresponds to FIGO stage IVA if detected. Similarly, rectoscopy is performed if bowel involvement is suspected (bleeding per rectum, extensive dorsal tumor). These examinations are not routinely performed for every tumor today, as the hit rate is low in the absence of suspicion and imaging usually provides sufficient information.

    Reference:

    1. Oncology Guidelines Program (German Cancer Society, German Cancer Aid, AWMF): S3 Guideline Diagnosis, Therapy, and Follow-up of Patients with Cervical Carcinoma, Long Version, 2.2, 2022, AWMF Registry Number: 032/033OL
    2. Fehm T, Beckmann MW, Mahner S, Denschlag D, Brucker S, Hillemanns P, Tempfer C; Uterus Commission of the AGO and the AGO Working Group. Statement of the Uterus Commission of the Gynecological Oncology Working Group (AGO) on Surgical Therapy for Patients with Stage IA2-IIB1 Cervical Cancer. Geburtshilfe Frauenheilkd. 2023 Oct 5;83(10):1199-1204. doi: 10.1055/a-2160-3279. PMID: 37808259; PMCID: PMC10556864.
    3. Bipat, S., et al., Computed tomography and magnetic resonance imaging in staging of uterine cervical carcinoma: a systematic review. Gynecol Oncol, 2003. 91(1): p. 59-66.
    4. Horn, L.C., et al., The 2019 FIGO classification for cervical carcinoma-what's new? Pathologe, 2019. 40(6): p. 629-635.
    5. Dappa, E., et al., The value of advanced MRI techniques in the assessment of cervical cancer: a review. Insights Imaging, 2017
    6. Woo, S., et al., Magnetic resonance imaging for detection of parametrial invasion in cervical cancer: An updated systematic review and meta-analysis of the literature between 2012 and 2016. Eur Radiol, 2017.
  3. Pap smear findings and diagnostic approach

    Pap Smear Classification (Munich Nomenclature III) and Recommended Procedure

    Pap FindingMeaningHPV Test RequiredRecommended Procedure
    Pap 0Insufficient material – Repeat requiredNot relevantRepeat the smear within 3 months
    Pap INormal findingNot relevantRoutine check at the recommended interval
    Pap II-aNormal finding with abnormal historyNot mandatory, cytological controlCytological control after 6-12 months
    Pap II-eEndometrial cells in women >40 years outside the first half of the cycleNot mandatory, clinical controlClinical control considering the history
    Pap II-gGlandular cell changes of unclear significanceYes, HPV positive → Colposcopy recommendedColposcopy recommended, possibly biopsy
    Pap II-pSquamous epithelial cell changes of unclear significanceYes, HPV positive → Colposcopy recommendedColposcopy recommended, possibly biopsy
    Pap III-eUnclear endometrial cell changesYesColposcopy with biopsy recommended
    Pap III-gSevere atypia of glandular epithelium, adenocarcinoma not excludedYesColposcopy with biopsy recommended
    Pap III-pUnclear squamous epithelial cell changes with suspicion of CIN 2/3YesColposcopy with biopsy recommended
    Pap III-xDoubtful glandular cells of unclear originYesFurther clinical diagnostics required
    Pap IIID1Mild dysplasia (CIN 1 / LSIL)Yes, HPV positive → Control or colposcopyControl in 6 months, if persistent → Colposcopy
    Pap IIID2Moderate dysplasia (CIN 2 / HSIL)Yes, HPV positive → Colposcopy with biopsyColposcopy with biopsy required
    Pap IVa-gSevere dysplasia / Adenocarcinoma in situ (AIS)YesColposcopy with biopsy recommended
    Pap IVa-pSevere dysplasia / Carcinoma in situ (CIN 3)YesColposcopy with biopsy recommended
    Pap IVb-gSuspicion of invasive adenocarcinomaYesHistological confirmation urgently required
    Pap IVb-pSuspicion of invasive squamous cell carcinomaYesHistological confirmation urgently required
    Pap V-eInvasive endometrial carcinomaYesOncological diagnostics and therapy planning
    Pap V-gInvasive adenocarcinomaYesOncological diagnostics and therapy planning
    Pap V-pInvasive squamous cell carcinomaYesOncological diagnostics and therapy planning
    Pap V-xMalignancy of unclear originYesOncological diagnostics and therapy planning

    Notes:

    • The suffixes “-p” stand for squamous epithelial cells, “-g” for glandular cells (e.g., from the cervical canal), “-e” for endometrial cells, and “-x” for unclear malignancies.​

    Reference: 

    1. Fehm TN, Wimberger P, Solomayer EF, Stübs FA, Beckmann, MW. Management of Cervical Dysplasia and Cervical Cancer in Pregnancy. TumorDiagnostik & Therapie 2022; 43(03): 167-179, doi 10.1055/a-1738-6512.
    2. Gajjar K, Martin-Hirsch PP, Bryant A, Owens GL. Pain relief for women with cervical intraepithelial neoplasia undergoing colposcopy treatment. Cochrane Database Syst Rev. 2016 Jul 18;7:CD006120. doi: 10.1002/14651858.CD006120.pub4.
    3. Griesser H, Marquardt K, Jordan B, Küppers V, Gieseking F, Kühn W (for the Coordination Conference Cytology). Cervical Cytology: The Procedure for Abnormal Findings - Commentary on the Munich Nomenclature III. Frauenarzt 2015; 56 (1): 10-13.
  4. Colposcopy

    Colposcopic Findings and Their Significance According to IFCPC Nomenclature (2011)

    Finding CategoryColposcopic AspectSignificance / Interpretation
    Normal FindingsThin, homogeneous squamous epithelium, sharp transformation zone, regular vascular pattern, glandular ducts, Nabothian cystsPhysiological, no indication of dysplasia
    Unremarkable ChangesEdematous epithelium, inflammatory changes, atrophic squamous epithelium, metaplasiaNo direct suspicion of dysplasia, follow-up in 3-6 months if abnormalities persist
    Minimal (Minor) Changes (Grade 1)Delicate, acetowhite epithelium, fine punctation or fine mosaicIndication of CIN 1 (mild dysplasia). Follow-up or HPV testing recommended
    Significant (Major) Changes (Grade 2)Dense, opaque acetowhite epithelium, coarse mosaic, coarse punctation, "inner border sign", "ridge sign", sharp demarcationIndication of CIN 2-3 or higher-grade dysplasia (HSIL). Biopsy or conization necessary
    Pathological / Highly Suspicious FindingsAcetowhite areas with sharp demarcation, iodine-negative areas, atypical vascular proliferations, exophytic tumor mass, atypical vessels, lesions bleeding on contactSuspicion of microinvasion or invasive carcinoma → Immediate biopsy, staging required
    Non-specific FindingsLeukoplakia (keratosis, hyperkeratosis), erosion, Schiller's test (Lugol's test)No clear dysplasia assignment, requires individual evaluation
    Additional FindingsCondylomas, endometriosis, ectocervical or endocervical polyps, postoperative changes (scarred cervix, vaginal blind pouch)Dependent on clinical context, often harmless, possibly requires histological clarification

    Transformation Zones According to IFCPC (2011)

    Transformation Zone TypeDefinitionRelevance for Diagnosis/Therapy
    TZ Type 1Completely ectocervical transformation zone, fully visibleGood visibility, no restrictions for biopsies or treatment
    TZ Type 2Partially endocervical transformation zone, but fully visibleMay contain endocervical components, biopsies possible but potentially more difficult
    TZ Type 3Transformation zone deep in the cervical canal, not fully visibleLimited visibility, possibly requires diagnostic excision

    Diagnostic Tests in Colposcopy

    TestPrincipleSignificance for Diagnosis
    Acetic Acid Test (Acetic Test)3-5% acetic acid is applied to the cervixDysplastic cells contain less glycogen and appear white (acetowhite areas), the denser and more sharply demarcated, the more suspicious for CIN 2-3 or carcinoma.
    Iodine Test (Schiller's Test)Cervix is coated with Lugol's solution (iodine)Normal squamous epithelium stores glycogen and stains dark brown, while dysplastic, inflammatory, or carcinomatous areas remain iodine-negative (light or yellowish).
    Leukoplakia TestApplication without prior acetic acid or iodineKeratinized areas (leukoplakias) appear as white, sharply demarcated lesions, which are not always dysplastic but need clarification.

    Reference:

    1. Bornstein J, Bentley J, Bösze B et al. (2012a) 2011 colposcopic terminology of the International Federation for Cervical Pathology and Colposcopy. Obstet Gynecol 120: 166–72
    2. Bornstein J, Sideri M, Tatti S. Walker P, Prendiville W, Haefner HK (2012b) 2011 Terminology of the vulva of the International Federation for Cervical Pathology and Colposcopy. J Low Genit Tract Dis 16: 290–95
    3. Girardi F, Frey Tirri B, Küppers V, Menton M, Quaas J, Reich O (2012) New colposcopic IFCPC nomenclature of the cervix uteri (Rio de Janeiro 2011). Der Frauenarzt 53: 1064–1066
    4. Quaas J, Reich O, Frey Tirri B, Küppers V (2013) Explanation and use of the colposcopy terminology of the IFCPC (International Federation for Cervical Pathology and Colposcopy) Rio 2011. Geburtsh Frauenheilk 73: 904–907
    5. Walker P, Dexeus S, De Palo G, Barrasso R, Campion M, Girardi F, Jakob C, Roy M (2003) International terminology of colposcopy: an updated report from the International Federation for Cervical Pathology and Colposcopy. Obstet Gynecol 101: 175–7
  5. literature search

    Literature search on the pages of pubmed.