ABNORMAL PAP/CERVICAL SMEAR

ABNORMAL PAP/CERVICAL SMEAR - Jeremy Golding, MD
BASICS
DESCRIPTION
• The Papanicolaou (Pap) smear is a screening test for cervical cellular pathology. In many laboratories, automated cervical screening complements the Pap smear or supersedes it.
• Abnormal cervical smear results can range from benign cellular changes to suggestion of invasive cancer.
• System(s) Affected: Reproductive
ALERT
Cervical cancer arises from a sexually transmitted disease (STD) caused by human papilloma virus (HPV) (1)[A].
Geriatric Considerations
Less frequent, except in the unscreened population
Pediatric Considerations
Transient Pap smear abnormalities are very common in adolescents, but exceedingly rare before initiation of sexual activity.
Pregnancy Considerations
Squamous intraepithelial lesions can progress during pregnancy, but often regress postpartum.
GENERAL PREVENTION
• HPV Immunization of girls and women prior to sexual debut
• Delay 1st intercourse beyond early adolescence
• Monogamous relationship for both partners
• Smoking cessation
• Adequate antioxidant-rich food intake has been associated with decreased risk
• Obtain routine Pap smears; HPV changes occur ~3 years after initiation of sexual intercourse
• Use barrier methods of birth control if nonmonogamous relationship
• Discontinue Pap smears after age 65-70 in women with recent normal screening and not otherwise at high risk for cervical cancer
EPIDEMIOLOGY
Predominant age: Can occur at any age
• Incidence of CIN3 peaks between ages 25 and 29; invasive disease peaks 15 years later.
Incidence
• Low-grade squamous intraepithelial lesion ranges from 2-3% of all Pap smears
• High-grade squamous intraepithelial lesion and invasive cancer present on 1% of Pap smears
• Other reactive, reparative, and ASC-US (atypical squamous cells of undetermined significance) results are difficult to assess because of the lack of reporting mechanisms
RISK FACTORS
• Cigarette smoking
• Possible deficiency of antioxidants
• Early age of intercourse
• Multiple sexual partners
• Some correlation to low socioeconomic level
• Intercourse with a high-risk male partner
• Human papilloma virus (HPV) infection
• Immunosuppressed
• Human immunodeficiency virus (HIV) infection (associated with earlier and more rapidly progressive cervical disease)
ETIOLOGY
• HPV DNA is found in virtually all cervical carcinomas and precursor lesions worldwide (2)[C]:
- HPV viral types 16, 18, 31, 35, 45, 51, 52, 56, and 58 are common high-risk or oncogenic virus types for cervical cancer.
- HPV viral types 6, 11, 42, 43, and 44 are considered common low-risk types, and cause genital warts.
• HPV DNA of high-risk viral types is integrated into the human cervical cell DNA.


DIAGNOSIS
SIGNS AND SYMPTOMS
• Frequently no symptoms
• Occasionally external genital HPV lesions
• Occasionally vaginal discharge related to STD
• Rarely: Vaginal bleeding related to a malignant lesion
TESTS
Lab
• Bethesda System for reporting Pap/cervical smear results
- Specimen adequacy
• Presence of endocervical cells
- Negative for intraepithelial lesion or malignancy
- Epithelial cell abnormalities
• ASC: Atypical squamous cells
• ASC-US: ASC of undetermined significance
• ASC-H: Atypical cells cannot exclude high-grade squamous intraepithelial lesion (SIL)
• LSIL: Low-grade SIL (Combines mild dysplasia and CIN1 with HPV)
• HSIL: High-grade SIL
• Squamous cell carcinoma
- Glandular cells
• AGC: Atypical glandular cells
• AGCs of undetermined significance
• Atypical glandular cells, favor neoplasia
• Endocervical adenocarcinoma in situ
• Adenocarcinoma
• ThinPrep is a fluid-based collection and thin-layer preparation for cervical cancer screening.
• Sensitivity of a single Pap smear for HSIL ~70%; specificity of ~90%
Diagnostic Procedures/Surgery
• Colposcopy with visually directed biopsy generally recommended when any of the following are present
- Initial Pap smear with LSIL or worse (adolescents may not require unless persistent)
- ASC-US present on 2 Pap smears 4-6 months apart
- ASC-US can be followed with (reflex) HPV hybrid capture 2 test
 If positive for high-risk viral type: Colposcopy.
 If negative for high-risk viral type: Repeat Pap smear in 1 year
- ASC-H needs colposcopic evaluation
- Any abnormal or suspicious lesion of the cervix or vagina that is visualized by the eye
- Atypical glandular cells (mandate colposcopy and uterine sampling)
- LSIL/CIN1 in an adolescent may be a self-limited HPV infection and can be followed with repeated Pap smear at 6 and 12 months
• HPV viral typing
- Hybrid capture 2 test has 2 viral type probes: A low-risk probe and a high-risk probe.
- High-risk probe can be used to identify patients with ASC-US who need colposcopy follow-up.
- HPV typing may be used in combination with Pap smear for women 30. Women with negative cytology and negative for high-risk HPV may be followed every 3 years. Women with persistent positive high-risk HPV but negative cytology should undergo colposcopy.
• Loop electrosurgical excision procedure (LEEP)
• Cone biopsy
• Cervicography: Photographic evaluation of cervix
Pathological Findings
• Atypical squamous or columnar cells
• Coarse nuclear material
• Increased nuclear diameter
• Koilocytosis (HPV hallmark)
DIFFERENTIAL DIAGNOSIS
• Acute or chronic cervicitis
• HPV infection
• Cervical squamous intraepithelial neoplasia
• Cervical glandular neoplasia
• Invasive cervical malignancy
• Uterine malignancy (rare)
TREATMENT
GENERAL MEASURES
Office evaluation and observation
• Promote smoking cessation.
• Promote protected intercourse.
Diet
Promote increased intake of antioxidant-rich foods.
MEDICATION (DRUGS)
• Infective/reactive Pap smear
- Metronidazole 250 mg t.i.d. PO for 7 days
• Condyloma acuminatum
- Cryotherapy
- Podophyllin topically every 1-2 weeks
- Trichloroacetic acid, applied topically by a physician and covered for 5-6 days
• LSIL/CIN1: Observation with Pap smear repeated every 6 months may be appropriate for young women with LSIL, especially with confirmed CIN1.
SURGERY
• LSILs and HSILs and carcinoma in situ can be treated with outpatient surgery.
- Cryotherapy, laser ablation, LEEP/large loop excision of transition zone, or LEEP or cold-knife conization
• If cervical malignancy, see "Cervical Malignancy" topic
FOLLOW-UP
DISPOSITION
Outpatient
PROGNOSIS
• Generally excellent
• 1/2 of persistent infective, reactive, reparative, or ASC-US Pap/cervical smears will have more advanced lesions.
• Only a small percentage of LSILs will progress to more advanced lesion.
• Lesions discovered early are very amenable to treatment, with excellent results and few recurrences.
COMPLICATIONS
• Minor abnormalities on Pap/cervical smears can mask more advanced lesions.
• HSILs can progress to invasive cancer.
PATIENT MONITORING
High-risk HPV contact tracing
REFERENCES
1. Guide to Clinical Preventive Services: Report of the US Preventive Services Task Force 2003 update available at http://www.ahrq.gov/clinic/uspstf/ uspscerv.htm
2. American Cancer Society guideline for the early detection of cervical neoplasia and cancer. CA Cancer J Clin. 2002;52(6):342-362.
3. Wright TC Jr, Cox JT, Massad LS, et al. ASCCP-Sponsored Consensus Conference. 2001 Consensus Guidelines for the management of women with cervical cytological abnormalities. JAMA. 2002;287:2120-2129. (Update expected Spring 2007; will be posted at http://www.asccp.org/consensus.shtml).
4. Solomon S, Davey D, Kurman R, et al. The 2001 Bethesda System: terminology for reporting results of cervical cytology. JAMA. 2002;287:2114-2119.
5. Bishop JW, Marshall CJ, Bentz JS. New technologies in gynecologic cytology. J Reprod Med. 2000;45:701-719.
6. Canavan TP, Doshi NR. Cervical cancer. Am Fam Phys. 2000;61:1369-1376.
7. Apgar BS, Brotzman G. HPV testing in the evaluation of the minimally abnormal Papanicolaou smear. Am Fam Phys. 1999;59:2794-2801.