What are the treatment options for a patient with a Pap (Papanicolaou) smear positive for Human Papillomavirus (HPV) but negative for high-risk types 16, 18, and 45?

From the Guidelines

For a patient with a Pap smear positive for Human Papillomavirus (HPV) but negative for high-risk types 16,18, and 45, the recommended approach is to follow-up without treatment or consider treatment using ablative or excisional modalities, with a preference for follow-up with repeat Pap test at 6 and 12 months or HPV testing at 12 months 1.

Key Considerations

• The patient's HPV status is positive but does not include the high-risk types 16,18, and 45, which are commonly associated with cervical cancer.
• The management guidelines for women with cervical intraepithelial neoplasia (CIN) recommend follow-up without treatment or treatment using ablative or excisional modalities for women with biopsy-confirmed CIN-1 1.
• The preferred follow-up approach is to perform a repeat Pap test at 6 and 12 months or HPV testing at 12 months, with referral to colposcopy if repeat cytology shows ≥ASC or high-risk HPV DNA positive 1.

Treatment Options

• Ablative modalities such as cryotherapy or laser ablation may be considered for treatment of CIN-1, although excisional modalities like LEEP are also acceptable 1.
• The decision to treat persistent CIN-1 should be based on patient and provider preferences, taking into account the potential risks and benefits of treatment 1.

Follow-up and Surveillance

• After treatment, follow-up using either cytology or a combination of cytology and colposcopy at 4- to 6-month intervals until at least 3 cytologic results are negative is recommended 1.
• Annual cytology follow-up is recommended after 3 negative cytologic results are obtained, with HPV DNA testing performed at least 6 months after treatment as an acceptable option for surveillance 1.

Important Considerations

• The natural history of CIN-2 and CIN-3 lesions indicates that these lesions are more likely to persist or progress than to regress, highlighting the importance of close follow-up and surveillance 1.
• HPV testing has been proposed as a strategy for screening, triage of mildly abnormal Pap smears, or risk assignment, although its role in secondary prevention strategies for cervical cancer is still being researched 1.

From the Research

Treatment Options for Patients with Pap Smear Positive for HPV but Negative for High-Risk Types 16,18, and 45

• The treatment options for patients with a Pap smear positive for Human Papillomavirus (HPV) but negative for high-risk types 16,18, and 45 are not explicitly stated in the provided studies. However, the studies suggest that referral to colposcopy is a credible and feasible strategy for non-16/18 hrHPV-infected women with negative cytology 2.
• According to the study by 2, CIN 2+ lesions were detected in 6.5% of women with negative cytology, and CIN 3+ lesions were detected in 2.7% of women with negative cytology.
• Another study by 3 suggests that adding an HR-HPV test that detects one or more of the HR-HPV types 16,18, and 45 in conjunction with cytology could help identify women with an underlying cervical lesion who have an elevated risk of developing severe cervical lesions.
• The study by 4 evaluated the use of Aptima HPV E6 and E7 mRNA assay combined with Aptima HPV 16 and 18 or 45 genotype assay as a means of cervical cancer opportunistic screening, and found that women with Aptima HPV positive, especially those with Aptima HPV-GT positive, are more likely to have histological diagnosis of HSIL(+).
• The study by 5 proposed cervicography and HPV DNA testing as intermediate triage techniques for the management of patients with Pap smear showing minor-grade atypia, and found that only a negative cervicography (with any HPV DNA test result) was always associated with the absence of severe histologic lesions.

Colposcopy and Biopsy

• Colposcopy-guided biopsy is a recommended approach for non-16/18 hrHPV-infected women with negative cytology 2.
• The study by 2 found that CIN 2+ lesions were detected in 6.5% of women with negative cytology, and CIN 3+ lesions were detected in 2.7% of women with negative cytology.
• Another study by 6 found that high-risk HPV types 16/18 could be detected in 47.3% of squamous intra-epithelial lesions, including 50% of HSIL lesions.

HPV Testing

• HPV testing can be used as an adjunct to routine cytology screening programs to identify 'high risk' women who have concurrently negative Pap smears but may harbor oncogenic HPV infection and/or more likely to develop CIN lesions 6.
• The study by 4 found that Aptima HPV combined with Aptima HPV-GT is feasible as a means of cervical cancer opportunistic screening in tertiary hospitals.
• The study by 3 suggests that adding an HR-HPV test that detects one or more of the HR-HPV types 16,18, and 45 in conjunction with cytology could help identify women with an underlying cervical lesion who have an elevated risk of developing severe cervical lesions.