Which Human Papillomavirus (HPV) causes Low-grade Squamous Intraepithelial Lesion (LSIL) on Pap smear?

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From the Guidelines

Low-grade squamous intraepithelial lesion (LSIL) on Pap smear is most commonly caused by high-risk HPV types, particularly HPV 16, which has a prevalence of 23.6% among LSIL Pap tests. The development of LSIL is often associated with HPV infection, and the presence of high-risk HPV types increases the potential for progression to cervical cancer. According to 1, HPV types 16 and 18 are more commonly found in association with higher-grade lesions, and the prevalence of HPV 16 is 23.6% among LSIL Pap tests.

Some key points to consider in the management of LSIL include:

  • LSIL represents mild cellular changes that often resolve spontaneously within 1-2 years as the immune system clears the HPV infection 1
  • Management typically involves repeat Pap testing in 12 months or HPV testing, rather than immediate treatment
  • Persistent LSIL, especially when associated with high-risk HPV types, may require colposcopy for further evaluation
  • HPV vaccination before exposure can prevent infection with the most common cancer-causing types, though it cannot treat existing infections 1
  • Regular screening remains important for early detection of cervical abnormalities regardless of vaccination status

It's worth noting that the majority of LSIL cases are associated with high-risk HPV types, and the presence of these types increases the risk of progression to cervical cancer. Therefore, it's essential to monitor and manage LSIL cases carefully to prevent the development of more severe lesions. As stated in 1, the management of LSIL has been clarified with the addition of sensitive DNA testing for HPV types that are most associated with cervical cancer.

From the Research

HPV Types Associated with LSIL

  • The human papillomavirus (HPV) types associated with low-grade squamous intraepithelial lesions (LSIL) are primarily high-risk HPV types, particularly HPV 16 and 18 2.
  • A study found that HSIL at biopsy was most common when HPV 16/18 was present (32%) and when multiple subtypes were detected (46%) versus when non-16, non-18 high-risk HPV alone was present (16%) or high-risk HPV was negative (12%) 2.
  • Another study found that the prevalence of high-risk HPV was significantly greater in patients with LSIL, cannot rule out high-grade lesion (LROH) than in patients with atypical squamous cells, cannot rule out high-grade lesion (ASC-H) 3, 4.

HPV Negative LSIL

  • A small proportion of women with LSIL have negative HPV tests, with studies suggesting that 3-11% of women with LSIL were found to have HPV-negative results on both HPV tests 5.
  • The demographic characteristics of women with HPV-negative LSIL were consistent with those of a low-risk population, with many being age > 35 years and reporting no or only 1 recent sexual partner 5.
  • The absolute risk of a histologic diagnosis of cervical intraepithelial neoplasia (CIN) Grade 3/carcinoma during the 2-year trial was lower for women with HPV-negative LSIL (range, 2-4%) compared with the absolute risks for oncogenic HPV-positive women with LSIL (range, 13-19%) 5.

LSIL Management and Follow-up

  • The management of LSIL often involves colposcopy, with a study finding that 52% of respondents would perform colposcopy for a Papanicolaou test with HPV effects, and 86% for a Papanicolaou test with mild dysplasia/CIN 1 6.
  • Follow-up rates were higher for high-risk HPV-positive cotests (82%) than for high-risk HPV-negative cotests (54%) 2.
  • The highest HSIL rates were seen when HPV 16/18 was present (32%), with HSIL rates similar for those high-risk HPV-negative (12%) and non-16, non-18 high-risk HPV-positive (16%) 2.

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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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