Papanicolaou Smear

Etiology and Epidemiology

In the United States, the death rate due to cervical cancer has declined by more than 60% since the 1950s. In the past, cervical cancer was one of the most common cancers affecting women of childbearing age, but over time, its occurrence has significantly decreased. Today, it ranks as the 14th most common cancer among these women, indicating a marked reduction in both incidence and impact.

In 2010, approximately 12,000 women were diagnosed with cervical cancer, resulting in approximately 4000 deaths. Between 2002 and 2012, the rate of cervical cancer decreased by 1.3%, and deaths from cervical cancer decreased by 0.9%. In 2014, Hispanic women were reported to have the highest rate of cervical cancer diagnoses, whereas African-American women had the highest death rate from the disease.[5][6][7]

Cervical cancer is much more common in countries without widespread screening programs. More than 80% of cervical cancer cases are found in developing countries. Cervical cancer is still the third most common cause of cancer in women worldwide. Annually, there are approximately 528,000 new cases of cervical cancer, with 266,000 deaths. These statistics make it the second most common cause of cancer-related death in women.

Pathophysiology

In the 1980s, researchers discovered that nearly all cervical cancer cases were caused by human papillomavirus (HPV). There are more than 100 types of HPV, and 40 can be transmitted sexually, whereas 15 are considered high-risk HPV or cancer-causing. There are 2 subtypes of HPV—HPV 16 and 18, which are responsible for about 70% of cervical cancers worldwide.

Cervical infection with high-risk HPV is typically required for the development of cervical cancer. However, HPV infection alone is not sufficient for progression to neoplasia. Most infections with high-risk HPV are transient and do not progress to cervical intraepithelial neoplasia (CIN). A small percentage of women infected with high-risk HPV develop cervical cancer. Cigarette smoking, a weakened immune system, and HIV infection are all factors contributing to the persistence of HPV.[8][9][10][11]

Specimen Requirements and Procedure

In 2009, the American College of Obstetricians and Gynecologists (ACOG) recommended that women begin Pap smear screenings at 21. The ACOG also advises that women aged 21 to 29 undergo Pap smear testing every 3 years. For women aged 30 to 65, the ACOG recommends Pap smears with HPV testing every 5 years. Screening can generally be discontinued after 65. However, certain groups of women should be screened more frequently for cervical cancer compared to the general population, which include women infected with HIV; immunocompromised women, such as organ transplant patients; women exposed to diethylstilbestrol while in utero; and those previously treated for CIN 2, CIN 3, or cervical cancer.

In 2018, the United States Preventive Services Task Force revised its guidelines as follows:

• Grade A recommendation: Screening for cervical cancer every 3 years with cervical cytology alone in women aged 21 to 29.

• Grade A recommendation: Screening every 3 years with cervical cytology alone, every 5 years with hrHPV testing alone, or every 5 years with hrHPV testing combined with cytology (co-testing) in women aged 30 to 65.

• Grade D recommendation: No screening for cervical cancer in women younger than 21.

• Grade D recommendation: No screening for cervical cancer in women older than 65 who have had adequate prior screening and are not otherwise at high risk for the disease.

• Grade D recommendation: Screening for cervical cancer in women who have had a hysterectomy with removal of the cervix and do not have a history of a high-grade precancerous lesion or cervical cancer.

Diagnostic Tests

Women with epithelial cell abnormalities on Pap smear should be further tested with colposcopy and biopsy (see Image. Squamous Cells with Acute Inflammation). A colposcope is a binocular microscope that allows visual inspection of the cervix. Gross abnormalities visualized on colposcopy can then be biopsied for further classification.

Testing Procedures

There are 2 acceptable techniques for collecting the Pap smear—liquid-based and conventional. In both methods, a clinician inserts a speculum into the woman's vagina and identifies the cervix. The liquid-based method involves collecting cells from the transformation zone of the cervix using a brush and transferring the cells to a vial of liquid preservative. The conventional technique involves collecting cells from the transformation zone of the cervix using a brush and spatula, transferring the cells to a slide, and fixing the slide with a preservative. The liquid-based technique allows testing for HPV, gonorrhea, and chlamydia from a single collection. Theoretically, the liquid-based technique has the advantages of more straightforward interpretation, fewer unsatisfactory results, and the filtration of blood and debris.

Interfering Factors

Vaginal discharge, blood, and lubricants can interfere with the interpretation of Pap smears. When performing Pap smears, many healthcare professionals use water or a small amount of water-based lubricant to minimize patient discomfort.

Results, Reporting, and Critical Findings

Bethesda System for Reporting Cervical Cytology

The Bethesda System for Reporting Cervical Cytology is a standardized classification system used in the United States for interpreting Pap smear results and has been in place since 1988. The most recent update was made in 2014. This system provides clear guidelines for reporting and interpreting cervical cytology findings, which aids in the management and diagnosis of cervical abnormalities.

Components of the Bethesda system:

• Specimen type: Indicates whether the sample is conventional or liquid-based
• Specimen adequacy: Indicates whether the specimen is satisfactory or unsatisfactory for evaluation
• General categorization
  • Negative for intraepithelial lesion or malignancy
  • Other
  • Epithelial cell abnormality

•  Interpretation/results:
  • Negative intraepithelial lesion: No cellular evidence of neoplasia)
  • Nonneoplastic findings: Includes non-neoplastic cellular variations, reactive cellular changes, and glandular cells in post-hysterectomy
  • Organisms: Detection of Trichomonas vaginalis, bacterial vaginosis, Candida species, Actinomyces species, and cellular changes consistent with herpes virus and cytomegalovirus
  • Other
  • Endometrial cells in a woman older than 45

Epithelial cell abnormalities:

• Squamous cell:
  • Atypical squamous cells (ASCs)
    • ASCs of undetermined significance (ASC-US)             
    • Cannot exclude high-grade squamous intraepithelial lesion (ASC-H)
  • Low-grade squamous intraepithelial lesion: Mild dysplasia or CIN 1
  • High-grade squamous intraepithelial lesion: Moderate and severe dysplasia, corresponding to CIN 2 and CIN 3
  • With features suspicious for invasion if invasion is suspected
  • Squamous cell carcinoma

• Glandular cell:
  • Endocervical cells (not otherwise specified)
  • Endometrial cells (not otherwise specified)
  • Glandular cells (not otherwise specified)
  • Endocervical cells favor neoplastic
  • Glandular cells favor neoplastic
  • Endocervical adenocarcinoma in situ
  • Adenocarcinoma endocervical
    • Endometrial
    • Extrauterine
    • Not otherwise specified

• Other malignant neoplasms

Clinical Significance

Since the discovery of HPV subtypes causing most cervical cancer cases, 2 vaccines have been developed to reduce the incidence of new cervical cancer cases. The bivalent vaccine offers protection against HPV subtypes 16 and 18, whereas the quadrivalent vaccine provides protection not only against HPV 16 and 18 but also for subtypes 6 and 11, which cause 90% of genital warts. Ongoing research continues to focus on developing vaccines for the prevention of cervical cancer.

Quality Control and Lab Safety

A computer-aided automated device can interpret Pap smear specimens. When using a computer-aided system, the Bethesda System for Reporting Cervical Cytology requires documentation of the device and its results.

Enhancing Healthcare Team Outcomes

The interprofessional team plays a vital role in improving patient care and outcomes related to Pap smears. This collaborative approach involves various healthcare professionals, including gynecologists, primary care physicians, nurses, pathologists, and laboratory technicians. Each member contributes unique expertise, enhancing the quality of care provided to patients.

Collaboration begins with clear communication among team members regarding screening guidelines, patient history, and individual risk factors for cervical cancer. Regular interdisciplinary meetings allow the team to review and discuss cases, share insights on interpreting Pap smear results, and develop shared protocols for follow-up care based on findings.

In addition, ongoing interprofessional continuing education initiatives allow healthcare professionals to stay updated on best practices and emerging evidence. This shared learning experience fosters an environment where each team member understands their role in the care continuum and the importance of their contributions. By recognizing and valuing each team member's contributions, the interprofessional team can effectively flatten the hierarchy in healthcare, leading to improved patient outcomes and a more integrated approach to cervical cancer prevention and care.