Residency · Residency · Obstetrics Gynecology

Cervical Cancer Screening and Colposcopy

Epidemiology of Cervical Cancer

Cervical cancer is the most common gynecologic cancer worldwide and the fourth most common cancer in women globally. In the United States, approximately 13,000 new cases and 4,000 deaths occur annually. Almost all cases are caused by persistent high-risk HPV infection, with HPV 16 and 18 accounting for approximately 70% of cervical cancers. The main histologic types are squamous cell carcinoma (70 to 80%) and adenocarcinoma (20 to 25%). Screening programs have produced a dramatic decrease in incidence in screened populations through early detection and treatment of precursor lesions.

Current Screening Guidelines

USPSTF / ACS / ACOG Recommendations

For women aged 21 to 29, cervical cytology (Pap smear) alone every 3 years is recommended. HPV testing is not recommended in this age group because of the high prevalence of transient HPV infections. For women aged 30 to 65, three strategies are acceptable: cervical cytology alone every 3 years, HPV testing alone (primary HPV screening) every 5 years, or co-testing with cytology plus HPV testing every 5 years. After age 65, screening is discontinued if there has been adequate prior negative screening, defined as three consecutive negative cytologies or two consecutive negative co-tests within 10 years with the most recent within 5 years. After hysterectomy with removal of the cervix, screening is discontinued if there is no history of CIN 2 or higher.

ACS 2020 Updated Guideline

The ACS 2020 update recommends initiating screening at age 25 with primary HPV testing every 5 years as the preferred strategy. Co-testing every 5 years or cytology alone every 3 years are acceptable alternatives. This represents a shift toward HPV-based screening as the primary approach.

Special Populations

HIV-positive women should begin screening at the time of HIV diagnosis regardless of age, with cytology at baseline and 12 months, then every 3 years if normal. Immunosuppressed patients require more frequent screening, typically annually. HPV-vaccinated women follow the same screening guidelines as unvaccinated women. Women with prior CIN 2/3 treatment require enhanced surveillance for 25 years per ASCCP guidelines. Women exposed to diethylstilbestrol require annual cytology and careful vaginal examination.

Cervical Cytology Interpretation (Bethesda System)

Squamous Cell Abnormalities

The Bethesda system classifies squamous abnormalities in ascending severity. ASC-US refers to atypical squamous cells of undetermined significance. ASC-H refers to atypical squamous cells that cannot exclude HSIL. LSIL is a low-grade squamous intraepithelial lesion encompassing HPV effect and CIN 1. HSIL is a high-grade squamous intraepithelial lesion encompassing CIN 2 and CIN 3. SCC denotes squamous cell carcinoma.

Glandular Cell Abnormalities

AGC refers to atypical glandular cells, specified as endocervical, endometrial, or not otherwise specified. AGC favor neoplasia denotes atypical glandular cells favoring neoplastic origin. AIS is adenocarcinoma in situ. Adenocarcinoma is classified as endocervical, endometrial, or not otherwise specified.

<image>Flowchart of the Bethesda cytology classification system showing the spectrum from normal to invasive carcinoma for both squamous (ASC-US, ASC-H, LSIL, HSIL, SCC) and glandular (AGC, AGC favor neoplasia, AIS, adenocarcinoma) cell abnormalities, with corresponding histologic correlates (CIN 1, CIN 2, CIN 3)</image>

ASCCP Risk-Based Management Consensus Guidelines (2019 Update)

Paradigm Shift

The 2019 ASCCP guidelines represent a fundamental shift: management is now based on the estimated risk of CIN 3 or worse rather than on individual test results alone. Risk is determined by the combination of current test results and prior screening history. Equal management is applied for equal risk, regardless of what combination of tests produced the risk estimate. The clinical action thresholds are as follows: a risk below 0.15% warrants return to routine screening at 5 years; 0.15 to 0.54% warrants return in 1 year; 0.55 to 3.9% warrants return in 1 year with some cases warranting colposcopy; 4.0 to 24% warrants colposcopy; 25 to 59% warrants colposcopy with biopsy or treatment; and 60% or above warrants treatment (excision preferred) or colposcopy with biopsy.

Key Management Scenarios

For ASC-US, reflex HPV testing is performed. If HPV-negative, the patient returns to routine screening. If HPV-positive, colposcopy is indicated. For ages 21 to 24, repeat cytology in 1 year is appropriate. For LSIL in women aged 25 and older, colposcopy is indicated, with HPV testing reflexed; if HPV-negative, return in 1 year may be acceptable. For ages 21 to 24, repeat cytology in 1 year is appropriate. ASC-H requires colposcopy at any age. HSIL warrants colposcopy, with immediate excision acceptable for non-pregnant patients aged 25 and older (expedited treatment). For ages 21 to 24, colposcopy with biopsy is performed, and observation is acceptable for CIN 2. AGC requires colposcopy with endocervical curettage. Endometrial biopsy is added if the patient is aged 35 or older or has abnormal uterine bleeding. AGC favor neoplasia or AIS requires an excisional procedure regardless of colposcopic findings.

Colposcopy

Indications

Colposcopy is indicated for abnormal cervical cytology meeting the threshold per ASCCP guidelines, positive HPV 16/18 with any cytology result, persistent HPV infection, unexplained abnormal cervical appearance, and follow-up of previously treated CIN.

Equipment and Setup

The colposcope provides binocular magnification at 4 to 25 times with a green filter. Required supplies include a speculum, tenaculum, biopsy forceps (Tischler or Kevorkian), and an endocervical curette. Solutions used include 3 to 5% acetic acid and Lugol iodine for the Schiller test. Monsel paste (ferric subsulfate) or silver nitrate is used for hemostasis.

Technique

The procedure is explained and consent is obtained. A speculum is inserted and the entire cervix is visualized. Normal saline is applied first to assess for leukoplakia and atypical vessels. Acetic acid at 3 to 5% concentration is then applied, with 1 to 2 minutes allowed for changes to develop. The entire transformation zone is systematically evaluated. Lugol iodine is applied for the Schiller test: normal glycogen-containing squamous epithelium stains dark brown, while abnormal areas remain unstained (Schiller-positive).

Transformation Zone Types

Type 1 has the entire squamocolumnar junction visible on the ectocervix. Type 2 has the squamocolumnar junction partially within the endocervical canal but fully visible with manipulation. Type 3 has the squamocolumnar junction within the endocervical canal and not fully visible. The adequacy of colposcopy depends on visualizing the entire squamocolumnar junction.

Colposcopic Findings

Normal

Normal findings include smooth, pink squamous epithelium, columnar epithelium appearing grape-like and red, and a normal transformation zone with nabothian cysts and squamous metaplasia.

Abnormal (Suggestive of Dysplasia)

Acetowhite epithelium appears as white change after acetic acid application, with thicker and denser changes suggesting higher grade lesions. Punctation presents as a fine or coarse stippled capillary pattern, with coarse punctation suggesting high-grade disease. Mosaicism is a tile-like vascular pattern, again graded as fine (low-grade) or coarse (high-grade). Atypical vessels with irregular, bizarre branching patterns suggest invasive disease. Sharp borders and well-defined margins suggest higher grade lesions. The internal border sign, a raised border within an acetowhite lesion, suggests CIN 3.

Suggestive of Invasion

Findings suggestive of invasion include dense acetowhite change with irregular surface contour, atypical or corkscrew vessels, necrosis, ulceration, friable tissue, and exophytic or endophytic mass.

<image>Colposcopic images comparing normal transformation zone with nabothian cysts, low-grade findings (faint acetowhite change with fine punctation), high-grade findings (dense acetowhite with coarse mosaicism and sharp margins), and invasive cancer (atypical vessels, irregular surface, ulceration)</image>

Biopsy Protocols

Targeted biopsies are taken from the most abnormal-appearing areas. Multiple biopsies increase detection, and ASCCP recommends biopsying all distinct lesions with 2 to 4 biopsies from acetowhite areas. Random biopsies of normal-appearing areas within the transformation zone may detect occult CIN. Endocervical curettage samples the endocervical canal and is required when the squamocolumnar junction is not fully visualized, when no lesion is identified on colposcopy, or when glandular cytology is abnormal. ECC is contraindicated in pregnancy. A hemostatic agent is applied to biopsy sites.

Management of Histologic Findings

CIN 1 (Low-Grade Cervical Dysplasia)

CIN 1 represents HPV infection, and 60 to 80% of cases regress spontaneously within 2 years. Observation with co-testing or HPV testing at 12 months is preferred. Treatment is offered only if the lesion persists for 2 years or more.

CIN 2 (Moderate Dysplasia)

Management depends on age and reproductive goals. For women aged 25 and older or those not desiring fertility, treatment with excision or ablation is recommended. For women aged 21 to 24 or those desiring fertility preservation, observation is acceptable with colposcopy and cytology every 6 months for up to 2 years, provided the entire lesion and squamocolumnar junction are visible and the ECC is negative. If CIN 2 persists for 2 years, treatment is recommended.

CIN 3 (Severe Dysplasia / Carcinoma In Situ)

Treatment is recommended in virtually all cases. An excisional procedure is preferred over ablation because it provides a histologic specimen to rule out invasion.

Treatment Options

Excisional procedures include LEEP (loop electrosurgical excision procedure), which is the most commonly performed and can be done in the office or operating room, and cold knife conization, which is preferred for suspected AIS, recurrent dysplasia, or when thermal artifact may impair interpretation. Ablative procedures include cryotherapy (rarely used in the US but still used in low-resource settings) and thermal ablation (increasingly used globally). Ablation is only appropriate when the entire lesion is visible, there is no suspicion of invasion, colposcopy is satisfactory, cytology and histology are concordant, and the ECC is negative.

Adenocarcinoma In Situ (AIS)

Cold knife conization with negative margins is the minimum management. Hysterectomy is the definitive treatment because AIS is multifocal in 15 to 20% of cases. If fertility is desired, conservative management with cold knife conization and close surveillance is acceptable, though negative margins are required and residual AIS is found in approximately 10% of subsequent hysterectomy specimens even with negative conization margins.

<image>Diagram comparing excisional procedures for cervical dysplasia: LEEP showing the wire loop excising the transformation zone with electrosurgical current, and cold knife conization showing a scalpel cone excision of a deeper and wider specimen, with specimen orientation markers and endocervical margin highlighted</image>

Post-Treatment Surveillance

Follow-up involves HPV testing or co-testing at 6 and 12 months after treatment. If negative, annual HPV testing continues for 3 years, then every 3 years for a total of 25 years. Positive margins after excision prompt repeat testing at 6 months, with re-excision if CIN 2/3 is found on follow-up. Post-treatment patients never return to routine 5-year screening intervals.

Clinical Pearls

Primary HPV testing every 5 years starting at age 25 is the preferred screening strategy per the ACS 2020 guidelines, representing a shift from cytology-first approaches.

The ASCCP 2019 guidelines use CIN 3+ risk estimates to guide management rather than individual test results alone. The ASCCP management app is a useful tool for clinical decision-making.

Colposcopy adequacy depends on visualizing the entire squamocolumnar junction. When it is not visible (Type 3 transformation zone), endocervical curettage is mandatory.

Multiple targeted biopsies (2 to 4) from acetowhite areas significantly increase CIN detection compared with a single biopsy.

CIN 2 in patients under 25 can be observed with close surveillance because of high spontaneous regression rates of 40 to 60%.

AIS requires cold knife conization rather than LEEP because thermal artifact and skip lesions may impair margin assessment.

After treatment of CIN 2/3, enhanced surveillance continues for 25 years. These patients never return to routine screening intervals.

References

• ASCCP Risk-Based Management Consensus Guidelines (Perkins et al., J Low Genit Tract Dis. 2020;24:102-131)
• ACOG Practice Advisory: Cervical Cancer Screening (Updated 2021)
• ACS Guideline for Cervical Cancer Screening (Fontham et al., CA Cancer J Clin. 2020;70:321-346)
• USPSTF Recommendation Statement: Cervical Cancer Screening (2018)
• Massad LS et al. 2012 ASCCP Consensus Guidelines for the management of abnormal cervical cancer screening tests. J Low Genit Tract Dis. 2013
• WHO Guidelines for Screening and Treatment of Cervical Pre-cancer Lesions (2021)

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