# Cervical Cancer Screening and HPV Management

## Overview

Cervical cancer screening has dramatically reduced both the incidence and mortality of cervical cancer. Current guidelines emphasize extended screening intervals, HPV-based testing strategies, and risk-based management of abnormal results guided by the 2019 ASCCP consensus guidelines.

## HPV Biology and Vaccination

HPV types 16 and 18 are responsible for approximately 70% of cervical cancers, while types 6 and 11 cause 90% of genital warts. The 9-valent vaccine (Gardasil 9) provides coverage against types 6, 11, 16, 18, 31, 33, 45, 52, and 58. The vaccination schedule differs by age: children aged 9 to 14 receive 2 doses spaced 6 to 12 months apart, while those aged 15 to 26 receive 3 doses at 0, 1 to 2, and 6 months. Catch-up vaccination for ages 27 to 45 involves shared decision-making, as the benefit is diminished because most individuals in this age group have already been exposed to HPV. Importantly, vaccination does not change screening recommendations, as the vaccine does not cover all oncogenic HPV types.

## Screening Guidelines

### USPSTF 2018 / ACS 2020 Recommendations

Cervical cancer screening begins at age 21 regardless of the age of sexual debut. For women aged 21 to 29, the USPSTF recommends cytology (Pap smear) alone every 3 years, while the ACS prefers no screening until age 25. For ages 25 to 29, the ACS recommends HPV primary testing every 5 years as the preferred strategy. For women aged 30 to 65, three strategies are acceptable: HPV primary testing every 5 years (preferred by both USPSTF and ACS), co-testing with HPV and cytology every 5 years, or cytology alone every 3 years (least preferred).

| Age Group | USPSTF Recommendation | ACS Recommendation |
|-----------|----------------------|-------------------|
| <21 | No screening | No screening |
| 21-24 | Cytology alone every 3 years | No screening (ACS starts at 25) |
| 25-29 | Cytology alone every 3 years | HPV primary testing every 5 years (preferred) |
| 30-65 | HPV every 5 yrs, co-testing every 5 yrs, or cytology every 3 yrs | HPV primary testing every 5 years (preferred) |
| >65 | Discontinue if adequate prior screening | Discontinue if adequate prior screening  |  Screening can be discontinued after age 65 if there has been adequate prior negative screening, defined as 3 consecutive negative cytology results or 2 consecutive negative HPV or co-test results in the prior 10 years, with the most recent within 5 years. After hysterectomy with cervix removal for a benign indication and no history of CIN2 or worse, no further screening is needed. Immunocompromised women, including those with HIV, should begin screening within 1 year of sexual activity or by age 21, with annual cytology and co-testing after age 30. |

### Screening After Abnormal Results

Following treatment of CIN2 or CIN3, HPV-based testing should be performed at 6 months, 1 year, and 2 years, then annually until 3 consecutive negative results are obtained. Routine screening should then continue for 25 years, even past age 65.

## Cytology Interpretation (Bethesda System)

The Bethesda system classifies cervical cytology results. NILM indicates a result negative for intraepithelial lesion or malignancy. ASC-US denotes atypical squamous cells of undetermined significance. ASC-H indicates atypical squamous cells where high-grade lesion cannot be excluded. LSIL represents low-grade squamous intraepithelial lesion. HSIL indicates high-grade squamous intraepithelial lesion. AGC denotes atypical glandular cells, which require a more aggressive workup.

## ASCCP Risk-Based Management (2019)

### Paradigm Shift

The 2019 ASCCP guidelines introduced a fundamental paradigm shift: management is now based on the estimated risk of CIN3 or worse rather than on individual test results in isolation. Risk stratification incorporates both current test results and past screening history, and the same management action is applied for the same risk level regardless of which test combination produced it. The risk thresholds are as follows: below 0.15% CIN3+ risk warrants return to routine 5-year screening; 0.15 to 0.54% warrants 3-year follow-up; 0.55 to 3.9% warrants 1-year follow-up; 4.0 to 24% prompts colposcopy; 25 to 59% calls for colposcopy with a minimum of 2 biopsies; and 60% or above favors treatment (excision), though colposcopy with biopsy is also acceptable.

### Common Clinical Scenarios

#### HPV-Negative, Cytology Negative

This represents the lowest risk category, and the patient returns to routine screening in 5 years.

#### HPV-Positive, Cytology Negative (No HPV 16/18 Genotyping)

One-year follow-up with HPV-based testing or co-testing is appropriate. If HPV genotype 16 or 18 is positive, colposcopy should proceed.

#### ASC-US

HPV triage guides management: if HPV is negative, the patient returns to routine screening; if HPV is positive, colposcopy is indicated. Alternatively, reflex HPV testing from the same liquid-based specimen can be performed.

#### LSIL

If HPV is positive, colposcopy is indicated. If HPV is negative, which is uncommon, 1-year follow-up is appropriate. Most LSIL resolves spontaneously, with 60 to 80% clearing within 2 years, especially in young women.

#### ASC-H or HSIL

Colposcopy is recommended regardless of HPV status. When HSIL carries an immediate risk of 60% or above, excisional treatment is acceptable without prior biopsy as expedited treatment. For patients aged 21 to 24 with HSIL, colposcopy is preferred over immediate treatment because of higher regression rates in young women.

#### AGC (Atypical Glandular Cells)

AGC requires colposcopy with endocervical curettage, plus endometrial biopsy if the patient is 35 or older or has abnormal bleeding. AGC carries a higher risk of significant pathology than ASC-US and warrants thorough evaluation. HPV testing should be performed if not already done.

## Colposcopy

### Indications

Colposcopy indications are guided by the ASCCP risk thresholds described above. During the procedure, application of 3 to 5% acetic acid causes acetowhite epithelium to appear, indicating abnormal areas. Lugol iodine (Schiller test) identifies non-staining areas as abnormal, since normal glycogenated epithelium stains dark brown. All acetowhite lesions should be biopsied, with a minimum of 2 biopsies recommended to reduce sampling error. Endocervical curettage should be performed when no visible lesion is identified, when the colposcopy is unsatisfactory, or when AGC prompted the referral.

### Biopsy Results (Histology)

CIN 1 represents mild dysplasia and largely reflects the HPV cytopathic effect. It carries a high spontaneous regression rate and is managed with surveillance using HPV testing or co-testing at 1 year. CIN 2 represents moderate dysplasia. In women under 25 or those planning pregnancy, observation is acceptable because CIN 2 regression rates reach 40 to 60% in young women. In women 25 and older, treatment is preferred through excision or ablation. Immunostaining with p16 helps distinguish true high-grade lesions (p16-positive) from lesions that may be managed as CIN 1 (p16-negative). CIN 3 and AIS (adenocarcinoma in situ) require treatment with excision by LEEP or cold knife cone. AIS specifically requires excision rather than ablation to assess margins and rule out invasive adenocarcinoma.

## Treatment Procedures

LEEP (loop electrosurgical excision procedure) is the most common treatment, performed in the office under local anesthesia to excise the transformation zone. Cold knife cone biopsy provides deeper excision and is preferred for AIS and when precise histologic margin assessment is needed; it is performed in the operating room. Ablation with cryotherapy or thermal energy destroys abnormal tissue but is only appropriate when the entire lesion is visible, there is no suspicion for invasion, and the endocervical curettage is negative. Post-procedure instructions include avoiding intercourse, tampons, and douching for 4 weeks, with follow-up at 6 months.

## Cervical Cancer in Pregnancy

Colposcopy can be safely performed during pregnancy, but biopsy should only be obtained if invasion is suspected. Endocervical curettage is contraindicated in pregnancy. CIN 2 and CIN 3 should have treatment deferred until postpartum, with repeat colposcopy each trimester. Invasive cancer management depends on gestational age and stage and requires a multidisciplinary team.

<image>A screening algorithm flowchart for cervical cancer showing age-stratified entry points (21-29, 30-65, >65), the three acceptable screening strategies (cytology alone, co-testing, HPV primary testing), and the intervals for each. Include branches for special populations (immunocompromised, post-hysterectomy) and criteria for discontinuing screening.</image>

<image>The ASCCP risk-based management framework visualized as a risk threshold diagram showing the clinical action thresholds (routine screening, 3-year follow-up, 1-year follow-up, colposcopy, expedited treatment) with corresponding CIN3+ risk percentages. Include common test result combinations (HPV+/Cyt negative, ASC-US/HPV+, HSIL) mapped to their risk levels and recommended actions.</image>

<image>A visual guide to colposcopy findings showing normal transformation zone, acetowhite epithelium patterns (fine vs. coarse), punctation, mosaicism, and atypical vessels, correlated with the likely histologic grade (CIN1 vs CIN2/3). Include examples of satisfactory vs. unsatisfactory colposcopy (visualization of entire squamocolumnar junction) and biopsy technique.</image>

## Clinical Pearls

HPV primary testing every 5 years is the preferred screening strategy for ages 25 to 65, as it detects more precancerous lesions than cytology alone. The ASCCP risk-based management approach means that the same management applies regardless of which test produced the result, as long as the estimated CIN3+ risk is the same. Most HPV infections and LSIL clear spontaneously within 2 years, especially in women under 30, and overtreatment should be avoided. HPV 16 is the highest-risk genotype and warrants colposcopy even when cytology is negative. AGC requires more aggressive workup than ASC-US, including endometrial biopsy in women 35 or older or those with abnormal bleeding. Screening should continue for 25 years after treatment of CIN2 or worse, even past age 65. HPV vaccination does not eliminate the need for screening, as the vaccine does not cover all oncogenic HPV types. LEEP can be performed safely in the office setting and is the most common treatment for CIN2 and CIN3, though patients should be counseled about the small risk of preterm delivery in future pregnancies.

## References

- USPSTF Cervical Cancer Screening Recommendation Statement. JAMA. 2018
- Fontham ETH et al. ACS Guideline for Cervical Cancer Screening. CA Cancer J Clin. 2020
- Perkins RB et al. 2019 ASCCP Risk-Based Management Consensus Guidelines. J Low Genit Tract Dis. 2020
- Moscicki AB et al. Cervical Cancer Screening in Adolescents and Young Women. J Low Genit Tract Dis. 2020
- Saslow D et al. ACS-ASCCP-ASCP Cervical Cancer Screening Guidelines. CA Cancer J Clin. 2012