Introduction

Cervical cancer is a significant women's health problem worldwide. Most cases of cervical cancer occur in developing countries that have ineffective screening programs. The incidence and mortality of cervical cancer in the United States have been decreasing in the past 30 years due to widespread screening. In the United States, cervical cancer diagnosis is usually in women who have never received screening or received inadequate screening.[1] Human papillomavirus (HPV) is one of the most common risk factors for cervical cancer. There are over 100 different strains of HPV, and those considered of high risk are involved in the etiology of cancer. Screening guidelines for cervical cancer have been evaluated and adjusted considering the time required for disease progression. Screening methods of cervical cancer include cytology and HPV testing.[2]

Specimen Collection

Cervical cancer screening can be achieved using two methods the liquid-based or the conventional method. Both methods collect cells from the transformation zone of the cervix. The liquid-based method involves transferring cells into a vial of preservatives, which can undergoes further processing in a laboratory. The liquid-based technique allows for easier interpretation, filtering of excess debris, and more importantly fewer unsatisfactory results.  Another advantage of using the liquid-based technique includes using a single specimen to perform cytology, HPV testing and gonorrhea and chlamydia testing.[3]

In contrast, the conventional method of screening involves transferring cervical cells from the transformation zone directly to a slide and then fixing the specimen. Specimen interpretation may be difficult with the presence of blood, discharge and lubricant use.[4] Both methods of specimen collection have undergone study, and there was no statistical difference in the specificity or sensitivity for detecting cervical intraepithelial neoplasia.[5][6]

Indications

Cervical cancer screening guidelines have been established for the general population by three major organizations, including the American Cancer Society, the American Society for Colposcopy and Cervical Pathology and the American Society for Clinical Pathology. 

• For females younger than 21 years, no screening is recommended.
• In addition, for women aged 21-29 years, recommendations include cytology without HPV testing. Human papilloma virus is most commonly diagnosed in teenagers and young females in their twenties. Therefore, pap smears in this age group will cause abnormal findings. The majority of young women have an effective immune response that will clear the infection in 8 months or decrease the viral loads to undetectable levels.[5] The incidence of cervical cancer before age 20 is low (0.1% cases), and data has not illustrated that screening is effective in this age group.[7]
• For women aged 30-65 years, recommendations include cytology alone every three years or cytology with HPV testing every five years.
• For women who underwent total hysterectomy with no history of cervical dysplasia or cancer in the past 20 years, no screening is recommended.
• For women older than 65 years, no screening is necessary after adequate prior screening results. Two consecutive negative cytology results with negative HPV testing or three consecutive negative cytology results constitutes adequate previous prior screening results. Women with a prior history of cervical dysplasia or adenocarcinoma should continue screening for 20 years.[6]

Primary HPV testing for cervical cancer screening has specific indications established by ASCCP and Society of Gynecology Oncology [SGO].[6]

Primary HPV testing should not be used in females younger than 25 years, re-screening after a negative primary HPV test should not occur earlier than three years and genotype should be completed for all positive HPV results. There are no clear guidelines for using primary HPV testing for immunocompromised and HIV positive females.[6] If clinicians use primary HPV testing, only one test has been approved and should be used for this purpose.[6]

Potential Diagnosis

In the United States, screening results are reported using the Bethesda System of cervical cytology. Reports include specimen type, specimen adequacy, interpretation, adjunctive testing, and computer-assisted interpretation of cervical cytology.[6] The specimen type will define the method of collection used. Specimen adequacy will notify the clinician if the specimen was satisfactory for evaluation or if the specimen was rejected and not processed. Reports will also describe the presence or absence of the transformation zone and whether the clinician will need to repeat the specimen collection. If the specimen analysis was by an automated device, the device must be included in the report.

Normal and Critical Findings

A normal Pap test result begins with a statement of adequacy, followed by “negative for intraepithelial lesion or malignancy” (NILM).

Negative for intraepithelial lesion or malignancy findings include:

• Non-neoplastic cellular changes
• Reactive cellular changes
• Microorganisms including the following: Trichomonas vaginalis, Candida species, bacterial vaginosis, actinomyces and cellular changes due to Herpes simplex virus and Cytomegalovirus

Concerning findings include epithelial cell abnormalities and endometrial cells in women aged 45 years old or older. Endometrial cells found during cervical cancer screening may raise concern for endometrial hyperplasia, and further workup may be indicated.

Epithelial cell abnormalities are divided into two categories including squamous cell and glandular cell abnormalities. 

Squamous cell findings include:

• Atypical squamous cells of undetermined significance (ASCUS) or cannot rule out high grade (ASC-H)
• Low grade squamous intraepithelial lesion (LSIL) or cervical intraepithelial neoplasia (CIN1). These are mild, subtle cell changes, and most go away without treatment
• High-grade squamous intraepithelial lesions (HSIL) or CIN 2 or 3. Moderate and severe cell changes which require further testing or treatment
• Squamous cell carcinoma of the cervix

Glandular cell findings include:

• Atypical glandular cells of undetermined significance (AGUS),

• Atypical glandular cells
  • Not otherwise specified (NOS)
  • Favor neoplasia
• Endocervical adenocarcinoma in situ or adenocarcinoma

Epithelial cell abnormalities will need further workup and treatment based on the patient’s age and medical history.[6] 

Interfering Factors

Specific populations may have different screening indications due to risk factors that have associations with cervical cancer. Women diagnosed with HIV, immunocompromised states, exposure to diethylstilbestrol in utero and those treated previously for CIN 2, CIN 3 or cervical cancer will require more frequent screening.[6]

Patient Safety and Education

Patients should receive education regarding the limitations of screening and appropriate follow-up intervals. Annual well-woman exams should be recommended even if cervical cancer screening is not performed at the visit.[6][8] 

Protection from cervical cancer is the primary goal of screening. However, patients should receive counsel about other methods of prevention. Patients should be counseled on the risks factors, smoking cessation, safe sex practice to limit exposure to sexually transmitted infections and HPV vaccination. Administration of the HPV vaccine will not affect the frequency of screening and patient should be educated to return for age-based screening.

Clinical Significance

Cervical cancer screening is one of the best cancer prevention achievements. However, there continue to be women who are not compliant with screening recommendations. Many die from this preventable cancer due to inadequate screening. Public health efforts are available to increase access to screening with appropriate follow-up.[9]