What is the management for a patient with a Human Papillomavirus (HPV) negative result and two unsatisfactory Pap (Papanicolaou) smear results?

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Last updated: June 12, 2025View editorial policy

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From the Guidelines

For a patient with an HPV-negative result and two unsatisfactory Pap smear results, the recommended management is to repeat the Pap smear, as unsatisfactory cervical cytology tests should be repeated even for women with HPV-negative results 1. The management of such cases prioritizes ruling out any potential cervical abnormalities that could not be assessed due to the unsatisfactory nature of the previous smears. Key considerations include:

  • The HPV-negative status, which indicates a lower risk for high-grade cervical lesions, but does not negate the need for further evaluation due to the unsatisfactory smear results.
  • The importance of proper specimen collection to avoid another unsatisfactory result, emphasizing the use of both an endocervical brush and spatula to collect cells from the transformation zone.
  • Patient preparation, such as avoiding intercourse, douching, or vaginal medications for 48 hours before the test and scheduling the test when not menstruating, to improve the quality of the specimen. For women aged 30 years or older, colposcopy is also an option for further evaluation, especially if repeat smears remain unsatisfactory, as it allows for a directed biopsy to rule out invasive disease and determine the extent of any preinvasive disease 1. The approach to managing these patients should be guided by the principle of similar management for similar risks, with the goal of identifying and treating any potential cervical abnormalities while minimizing unnecessary procedures and anxiety for the patient.

From the Research

Management of HPV Negative but 2 Unsatisfactory Smear Results

  • The management for a patient with a Human Papillomavirus (HPV) negative result and two unsatisfactory Pap smear results is guided by specific recommendations 2.
  • According to the 2019 American Society of Colposcopy and Cervical Pathology management guidelines, patients with an unsatisfactory Papanicolaou (Pap) test and negative HPV cotest should undergo repeat age-based screening in 2 to 4 months 2.
  • However, a study suggests that women with unsatisfactory Pap test and negative HPV cotest may be safely called back at an interval longer than 4 months, as a negative HPV cotest in individuals with unsatisfactory Pap test predicted the lack of high-grade squamous intraepithelial lesion (HSIL) 2.
  • The rationale behind the initial recommendation is that a negative HPV test in the setting of an unsatisfactory Pap test may reflect an inadequate sample and therefore should not be interpreted as truly "negative" 2.
  • Other studies focus on the importance of HPV testing and Pap smear in detecting cervical epithelial precancerous lesions, highlighting the usefulness of these tools in routine screening for better treatment outcomes and reducing mortality rates 3, 4, 5.

Considerations for Follow-Up

  • Compliance with the recommended follow-up time of 2 to 4 months for women with unsatisfactory Pap test was found to be low (45.1%) 2.
  • Factors such as previous treatment of cervical intraepithelial neoplasia (CIN) may predict the presence of significant CIN, but this is more relevant in cases of discrepancy between Pap smear and biopsy results 6.
  • The decision on the follow-up interval should consider the individual patient's risk factors and the results of the HPV cotest and Pap smear 2, 5.

References

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

Research

Clinical correlation of cervical cancer screening using Pap smear test.

Journal of population therapeutics and clinical pharmacology = Journal de la therapeutique des populations et de la pharmacologie clinique, 2022

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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