01 Abnormal Pap

Pap

A pap smear is a screening test for cervical dysplasia where cells that are scraped from the transition zone (where squamous and columnar epithelium meet at the opening of the cervix) are examined under microscope. Page 2 of the following link provides the USPTF guidelines for cervical cancer screening.

Cellular grading of cervical dysplasia is done based on the histological pap smear findings, using the following grading system:

• Atypical squamous cells of undetermined significance (ASCUS)

• Atypical squamous cells, cannot exclude high-grade squamous intraepithelial lesion (ASC-H)

• Low-grade squamous intraepithelial lesion (LSIL)

• High-grade squamous intraepithelial lesion (HSIL)

ASCH

Atypical squamous cells, cannot exclude high-grade squamous intraepithelial lesion (ASC-H) characterizes cellular abnormalities in the cervical epithelium that likely consist of a mixture of true high-grade squamous intraepithelial lesion and other findings that mimic such lesions.

Patients with a pap smear showing ASC-H should undergo immediate colposcopy.

LSIL

Low-grade squamous intraepithelial lesion (LSIL) characterizes mild cellular dysplasia in the cervical epithelium.

LSIL in a patient who is 25 years old or older and HPV negative should be followed-up in 1 year with cytology and HPV co-testing to determine whether cervical intraepithelial neoplasia is present. If co-testing is both negative, co-testing should be done again in 3 years.

LSIL in a patient who is 25 years old or older and HPV positive (or has an unknown HPV status) should be investigated with colposcopy. The presence or absence of CIN2,3 will dictate management based on ASCCP guidelines.

LSIL in a patient who between 21 and 24 years of age should be followed-up in 12 months with repeat cytology. If negative, repeat again in 12 months and if repeat cytology is negative, the patient may return to routine screening. If cytology shows ASC-US or worse, colposcopy should be conducted.

HSIL

High-grade squamous intraepithelial lesion (HSIL) describes a pap smear finding of moderate or severe cellular dysplasia in the cervical epithelium. Because this is a scraping, it is impossible to determine whether this represents partial-thickness atypia, full-thickness atypia (carcinoma in situ), or carcinoma.

HSIL on a pap smear should be followed-up with colposcopy (including biopsies if indicated) to determine whether cervical intraepithelial neoplasia is present.

ASCUS

Atypical squamous cells of undetermined significance (ASCUS) characterizes cellular abnormalities in the cervical epithelium that are not explained by reactive changes and are not diagnostic of intraepithelial lesions.

According to the 2014 ASCCP guidelines, treatment of ASCUS (HPV unknown) involves one of the following treatment options:

1. Repeat pap in 12 months

2. HPV testing at the time of ASCUS diagnosis

A patient with an ASCUS pap who is HPV negative should undergo repeat cytology and HPV co-testing in 3 years.

A patient with an ASCUS pap who is HPV positive should undergo colposcopy.

If a patient with an ASCUS pap has an unknown HPV status and cannot be tested for HPV, repeat the pap smear in 12 months. If her repeat pap at 12 months is also ASCUS (or worse), then the appropriate treatment is colposcopy.

Women age 21-24 with ASCUS or LSIL should undergo repeat pap in 1 year. Reflex HPV testing is not indicated in this population, and colposcopy is only indicated if the lesion advances beyond LSIL.

Note: Women age <21 should not undergo pap smear regardless of whether they are sexually active, due to the increased prevalence of transitory, clinically insignificant cervical dysplasia in this population and the long-term harm caused by treatment of these clinically insignificant findings.

Colposcopy

Colposcopy is a diagnostic procedure where a dissecting microscope (colposcope) is used to obtain an illuminated and magnified view of the cervix for biopsy.

Acetic acid is used to improve visualization of abnormal areas as the solution causes metaplastic cells to reflect light and appear white, referred to as “acetowhite” changes.

In order to best detect cervical intraepithelial neoplasia, multiple biopsies are taken.

Colposcopic biopsy results are graded using a different system from pap smears:

• Cervical intraepithelial neoplasia-1 (CIN-1)

• Cervical intraepithelial neoplasia-2or3 (CIN-2 or 3)

• Invasive carcinoma

Cervical intraepithelial neoplasia-1 (CIN-1) is considered low-grade dysplasia found after colposcopy and describes dysplasia within the lower third of the cervical epithelium (farthest from the epithelial surface).

Treatment of CIN-1 varies by patient age and Pap smear findings prior to colposcopy.

It may include anything from repeat colposcopy every 6 months for two years (for patients age 21-24 with HSIL Pap prior to colposcopy) to repeat Pap with HPV co-testing in 12 months and again in 3 years if normal (for patients at least 25 years old with ASCUS or LSIL Pap prior to colposcopy). This algorithm is complex and unlikely to be tested on USMLE.

Cervical intraepithelial neoplasia-2 and 3 (CIN-2 and 3) is considered high-grade dysplasia found after colposcopy and describes dysplasia within the lower two-thirds of the cervical epithelium farthest from the epithelial surface (CIN-2), up to full thickness atypia (CIN-3).

Treatment of CIN-2 or 3 involves excision by loop electrocautery excision procedure (LEEP) or conization or laser ablation, with co-testing (cytology and endocervical curettage) at 12 and 24 months. However, co-testing should be repeated earlier (at 4-6 months) if CIN2,3 is identified at the margins. If negative for two visits, repeat three years later.

Squamous cell carcinoma refers to highly atypical cells with stromal invasion. For treatment see the cervical cancer topic.