Overview

Primary screening tool for cervical intraepithelial neoplasia (CIN) and cervical cancer.
Etiology: High-risk human papillomavirus (hrHPV types 16, 18, 31, 33).
Goal: Identify pre-malignant dysplasia (CIN 2/3) prior to malignant transformation.

Screening Guidelines (USPSTF / ACOG)

<21 years: No screening regardless of sexual activity initiation (high rate of transient infection & self-resolving dysplasia).
21–29 years: Pap smear (cytology) alone q3y.
- HPV co-testing is NOT recommended in this age group.
30–65 years: Options include:
- hrHPV co-testing + Cytology q5y (Preferred).
- Cytology alone q3y.
- hrHPV alone q5y.
>65 years: Discontinue screening if adequate negative prior screening:
- 3 consecutive negative cytology alone OR 2 consecutive negative co-tests within past 10 yrs (most recent within 5 yrs).
- AND no hx of CIN 2, CIN 3, or adenocarcinoma in situ (AIS) in past 20 yrs.
Post-Hysterectomy:
- Total Hysterectomy (cervix removed) for benign indications + no hx of CIN 2+: Discontinue screening.
- Subtotal Hysterectomy (cervix intact): Continue routine screening.
- Hysterectomy w/ hx of CIN 2+: Continue vaginal cuff screening for 20 years post-procedure.

HIV / Immunocompromised:
- Initial screening at HIV diagnosis (or within 1 yr of sexual onset).
- Screening schedule: Pap smear annually (or q3y if 3 consecutive normal results). Continue screening lifelong (do NOT stop at 65).
In Utero DES Exposure:
- Annual screening with cytology + thorough vaginal palpation (risk for Clear Cell Adenocarcinoma of vagina/cervix).

Normal squamous epithelial cells are present.

The cells with blue (cyanophilic) cytoplasm on the left of the image are intermediate cells (marked by blue dotted line).
The cell with the red (eosinophilic) cytoplasm on the right of the image is a superficial cell (marked by yellow dotted line).
Neutrophils can also be seen (small cells with a segmented nucleus).

Changes in squamous cells that do not qualify as squamous intraepithelial lesion (SIL) but are more significant than inflammatory or reactive changes.
Age 21–24:
- Repeat Pap in 12 months (preferred). c
- If repeat Pap is ASC-US/LSIL -> Repeat Pap again at 24 mo.
- Colposcopy indicated ONLY if persistent ASC-US/LSIL at 24 mo or if ASC-H/HSIL detected.
Age ≥25:
- Reflex HPV Testing (preferred).
- If hrHPV (+) -> Colposcopy.
- If hrHPV (-) -> Resume routine screening in 3 years.

Age 21–24: Repeat Pap in 12 months (Colposcopy contraindicated due to high spontaneous regression rates).
Age 25–29: Colposcopy.
Age ≥30:
- If hrHPV (-) -> Repeat Pap in 1 yr OR Colposcopy.
- If hrHPV (+) -> Colposcopy.

Age 21–24: Colposcopy.
Age ≥25:
- Colposcopy OR immediate LEEP (Loop Electrosurgical Excision Procedure) / excisional biopsy.

All ages: Colposcopy + Endocervical Curettage (ECC).
If Age ≥35 OR Risk factors for Endometrial Cancer (e.g., abnormal uterine bleeding, obesity, anovulation):
- Add Endometrial Biopsy (EMB).

Procedure	Clinical Indications	Notes / Key Points
Colposcopy	Follow-up for high-risk abnormal Pap (ASC-H, HSIL, AGC, or HPV+ ASC-US).	Visual inspection w/ acetic acid (acetowhite lesions) & Lugol iodine. Biopsy abnormal zones.
ECC	Evaluation of endocervical canal during colposcopy.	Contraindicated in pregnancy.
LEEP / Cone Biopsy	Diagnostic/Therapeutic for CIN 2/3, discordant biopsy vs cytology, or positive ECC.	Risks: Cervical stenosis, cervical insufficiency (preterm labor in future pregnancies).
EMB	AGC on Pap in patient ≥35 yo, or postmenopausal bleeding.	Evaluates endometrial lining for hyperplasia/carcinoma.

Safe in Pregnancy: Cytology, HPV testing, and Colposcopy (without endocervical sampling).
CONTRAINDICATED in Pregnancy:
- Endocervical Curettage (ECC) (risk of pregnancy disruption).
- Endometrial Biopsy (EMB).
- Excisional procedures (LEEP/Cone biopsy): Defer until postpartum unless invasive cervical cancer is strongly suspected.
If CIN 2/3 is confirmed during pregnancy -> Re-evaluate w/ Pap and colposcopy 6–12 weeks postpartum.

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