In an insurance/underwriting context, Pap testing improves long-term outcomes and can lower future claim severity and treatment-related costs. RGA recently launched new Pap test guidelines in its Global Underwriting Manual (GUM).
Cervical cancer is the fourth-most-common cause of cancer-related mortality among women worldwide. Cervical cytology (Pap testing) plays a key role in early detection and prevention. This article summarizes the epidemiology, pathogenesis, classification, screening strategies, and prognostic implications of Pap test abnormalities, with particular attention to HPV-driven risk assessment and its relevance to long-term outcomes.
Persistent infection with oncogenic human papillomavirus (HPV) types accounts for more than 99% of cervical cancer cases. HPV infection is common, with most sexually active women acquiring the virus at least once during their lifetime. While the majority of infections resolve spontaneously within 12 months, a subset persists and confers a significantly elevated risk of neoplastic transformation.1,2
HPV types 16 and 18 are the most carcinogenic, together accounting for approximately 70% of cervical cancers globally. Geographic variation in HPV prevalence and cervical cancer incidence reflects differences in screening access, vaccination coverage, and socioeconomic factors.3
A Pap test or Pap smear, also known as a cervical smear, is a diagnostic screening procedure used to identify abnormal or pre-cancerous changes in cervical cells, which may lead to cervical cancer. The predominant factor contributing to abnormal Pap smear results is infection with HPV. Persistent high-risk HPV infection is the main driver of clinically significant cervical screening abnormalities; therefore, HPV-based testing (primary HPV testing or co-testing) is central to the risk-based management framework.
The 2019 ASCCP framework emphasizes primary HPV testing over Pap smear because HPV-based testing provides the best basis for estimating a person’s current and future risk of cervical intraepithelial neoplasia (CIN) 3+ (pre-cancer/cancer), whereas cytology (a Pap test) has lower sensitivity and lower negative predictive value for long-term risk prediction.
In the U.S., around 4% of individuals who have cervical cancer screenings are diagnosed with CIN 1, while about 5% are found to have CIN 2 or 3.5
Cervical cytology indicates current risk of CIN, while oncogenic HPV subtypes are a sensitive predictor of both current and future CIN risk because HPV is a more sensitive test for predicting cervical pre-cancers.
The most common risk factors for pre-cancerous lesions, including CIN, are similar to the risk factors for more serious outcomes, such as adenocarcinoma and squamous cell carcinoma. This includes:9,10
Pap tests are used to screen for malignant and pre-malignant lesions of the cervix. The recommended age to begin cervical cancer screening has undergone significant revision over time, as the natural history of HPV infections and subsequent cervical dysplasia has been elucidated.
Pap test screening guidelines vary slightly by organization but generally align on starting at age 21 and continuing regularly until age 65, with options for Pap test alone, HPV testing, or co-testing.
Below are the current recommendations from the American College of Obstetricians and Gynecologists (ACOG) for each abnormal result.11
An incident HPV infection is defined as an HPV-positive test obtained following a prior HPV-negative test, whereas a persistent HPV infection is defined as the same HPV type detected in two consecutive screening tests.
HPV vaccines have emerged as a crucial tool for preventing precancerous genital lesions and cervical cancer linked to specific HPV types. Scientific societies strongly recommend administering HPV vaccination to children before the onset of sexual activity.12
A positive Pap test indicates abnormal cervical cells, often linked to HPV, but treatment depends on the severity (e.g., ASCUS, LSIL, HSIL) and requires follow-up.13
Treatment of CIN can be either excisional (i.e., conization) or ablative. Ablative modalities are solely for treatment, while excisional therapy provides diagnostic information as well as therapeutic benefit.
Prognosis is dependent on the following:14,15
The risk of overt cervical cancer is significantly higher when a woman has missed screening for more than 10 years.3
Cervical cancer prevention relies on effective identification, vaccination, and management of HPV-related disease. HPV-based testing has become central to modern screening strategies due to its superior ability to predict clinically significant cervical pathology. A clear understanding of the natural history and prognostic implications of Pap test abnormalities is essential for evidence-based clinical management and long-term risk assessment.
For insurance, Pap test/cervical screening serves as a risk mitigant. Early detection reduces the future incidence of advanced cervical cancer, treatment intensity, and associated claim severity (e.g., hospitalization, oncology, disability) and improves long-term survival. To learn more, view the PAP test guidelines update in RGA’s Global Underwriting Manual (GUM).
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