Assessment of Human Papillomavirus Non-16/18, Type-Specific Risk for Cervical Intraepithelial Neoplasia Grade 3 or Worse Among Women With Cervical Atypical Glandular Cells

Abstract

OBJECTIVE: To evaluate the risk for cervical intraepithelial neoplasia grade 3 (CIN 3) or worse (including adenocarcinoma in situ [AIS] and invasive cervical cancer) associated with non-16/18 human papillomavirus (HPV) types (other HPV) among women with atypical glandular cells (AGC) in cervical cytology. METHODS: This population-based cohort study evaluates the risk of CIN 3 or worse associated with other HPV types. Human papillomavirus genotyping was performed on Pap tests collected in Sweden from 341 women with AGC that were positive for other HPV types from February 17, 2014, to December 31, 2018. The women were followed for histopathologic outcomes using comprehensive registry linkages until December 31, 2019. Cumulative incidence proportions of CIN 3 or worse by specific HPV type were calculated using 1-minus Kaplan-Meier function. Hazard ratios (HRs) for CIN 3 or worse were generated using multivariate Cox regression. RESULTS: Of 341 women, 134 (39.3%) had CIN 3–AIS, but there were only five (1.5%) women in the cohort with invasive cervical cancer. Human papillomavirus 45 preceded 80.0% of invasive cervical cancer cases. Among women positive for HPV33, 82.9% (95% CI 58.0–97.3%) had CIN 3 or worse during follow-up. Positivity for HPV31 conferred the highest HR for CIN 3 or worse relative to other types, both in primary cytology and primary HPV screening (HR 2.71, 95% CI 1.47–5.00 and HR 3.41, 95% CI 1.95–5.96, respectively). CONCLUSION: Among non-16/18 HPV types in AGC, HPV31 and 33 had the highest risk for CIN 3 or worse, whereas most of the women with invasive cancer were positive for HPV45. Extended HPV genotyping may be helpful for the management of AGC.

Comprehensive overview of genotype distribution and prevalence of human papillomavirus in cervical lesions

“…Furthermore, HPV16 and HPV18 have been the most prevalent genotypes identified in AGC cases. 69 Yilmaz et al reported the five most common types in their cohort were HPV16 (19.8%), HPV18 (15.6%), HPV31 (9.5%), HPV45 (5.8%) and HPV52 (4.4%), while Tang et al identified HPV16 (16.7%), HPV18 (9.5%), HPV52 (7.1%), HPV58 (6.6%) and HPV53 (3.6%) in their study population. 66 69 A study from Italy revealed HPV58 and HPV31 to be the most common types after HPV16 and HPV18.…”

“… 69 Yilmaz et al reported the five most common types in their cohort were HPV16 (19.8%), HPV18 (15.6%), HPV31 (9.5%), HPV45 (5.8%) and HPV52 (4.4%), while Tang et al identified HPV16 (16.7%), HPV18 (9.5%), HPV52 (7.1%), HPV58 (6.6%) and HPV53 (3.6%) in their study population. 66 69 A study from Italy revealed HPV58 and HPV31 to be the most common types after HPV16 and HPV18. 70 In the study of AGC by Pradhan et al , the most severe lesion was CIN2/3 (5.6%), followed by endometrial carcinoma (5.5%) and endocervical lesions (1.3% for AIS, 0.6% for ADC) after histological follow-up within 1 year.…”

“…Yilmaz et al revealed that HPV31 and 33 had a higher risk of CIN3+, with HPV45 infection harbouring an increased risk of cervical carcinoma. 69 Schiffman et al found that the presence of HPV45 alone, or in combination with AGC cytology, indicated an elevated risk of AIS and cervical carcinoma. 72 Tang et al reported the increasing risk of CIN2+ for the composite group of HPV16/18/58/52/53-positive cases among HR-HPV-positive AGC cases.…”