What are the next steps in management for a 65-year-old female with a positive Low-grade Squamous Intraepithelial Lesion (LSIL) on Pap smear and positive Human Papillomavirus (HPV) test?

From the Guidelines

For a 65-year-old female with LSIL on Pap smear and positive HPV testing, the recommended next step is colposcopy with directed biopsies, as this approach prioritizes the detection and potential treatment of high-grade lesions or cancer that may be present despite the LSIL diagnosis. This recommendation is based on the understanding that HPV persistence in women over 65 increases the risk of progression to higher-grade lesions or cervical cancer 1. The goal of colposcopy is to rule out high-grade lesions or cancer that might be missed on cytology alone.

Key Considerations

• The patient's age and positive HPV status indicate a higher risk for underlying high-grade lesions or cancer, necessitating a more thorough evaluation.
• Colposcopy with directed biopsies is the preferred method for evaluating abnormal Pap smear results in this context, as it allows for the direct visualization of the cervix and targeted sampling of potentially abnormal areas.
• If colposcopy is inadequate or unsatisfactory, or if the squamocolumnar junction is not fully visualized, a diagnostic excisional procedure such as LEEP (Loop Electrosurgical Excision Procedure) may be necessary.

Management Approach

• Following colposcopy, management will depend on biopsy results, ranging from surveillance with repeat co-testing in 12 months for confirmed LSIL to more aggressive treatment if higher-grade lesions are identified.
• The approach should be individualized based on the patient's overall health status, preferences, and the specific findings from the colposcopy and biopsy.

Evidence Basis

• The recommendation for colposcopy with directed biopsies in this scenario is supported by guidelines that emphasize the importance of thorough evaluation in the presence of abnormal Pap smear results and positive HPV testing, particularly in older women 1.
• While older studies may provide background information on the management of cervical lesions, the most recent and highest quality evidence should guide clinical decision-making 1.

From the Research

Management of LSIL with Positive HPV

• A 65-year-old female with a positive LSIL on Pap smear and positive HPV requires careful management to prevent the progression of cervical lesions.
• According to a study published in 2017 2, a positive HPV E6/E7 mRNA test result is associated with a higher risk of progressing to CIN2+ in the future, with a pooled relative risk of 3.08.
• The same study suggests that women with ASCUS or LSIL Pap smear and a positive HPV E6/E7 mRNA test result should be referred for colposcopy and strengthen follow-up promptly.

Colposcopic Examination and Biopsy

• A retrospective study published in 2002 3 found that patients with ASCUS or LSIL Pap smear exhibit a wide spectrum of histological findings, ranging from no pathologic abnormality to frequent high-grade CIN and invasive carcinoma in rare cases.
• The study recommends colposcopic examination for all women with a cytologic diagnosis of ASCUS and LSIL, followed by directed-punch biopsy and therapeutic indications.

Risk of CIN 2+ and CIN 3+

• A study published in 2013 4 estimated the 5-year risks of CIN 2+ and CIN 3+ among women with HPV-positive and HPV-negative LSIL Pap results.
• The study found that HPV-positive/LSIL women had a higher risk of CIN 2+ and CIN 3+ compared to HPV-negative/LSIL women, with 5-year risks of 19% and 6.1%, respectively.
• The study suggests that women with HPV-negative/LSIL might be managed similarly to those with ASC-US Pap results without knowledge of HPV testing, with retesting at 6 to 12 months rather than immediate colposcopy.

Postmenopausal Women with LSIL

• A study published in 2016 5 found that postmenopausal women with LSIL on cytology and a negative HRHPV test had a minimal risk of HSIL (CIN 2-3) on colposcopic biopsy.
• The study recommends reflex HPV testing as the best choice for patients who test positive for postmenopausal LSIL by Pap smear.

Cervical Cancer Screening in Low-Resource Settings

• A study published in 2011 6 evaluated the efficacy of Pap smear, HPV DNA testing, and colposcopy in cervical cancer screening in low-resource settings.
• The study found that combining Pap smear and HPV DNA testing increased the sensitivity and negative predictive value to 100%, and recommends that women with ASCUS and LSIL on cervical cytology should be subjected to HPV DNA testing and only referred for colposcopy if found positive.