Human Papillomavirus (HPV) Genotypes in Women with Cervical Precancer and Cancer at Kaiser Permanente Northern California

Abstract

Background The human papillomavirus (HPV) Persistence and Progression Cohort is a natural history study of carcinogenic HPV positive women. Here, we present the HPV genotypes found in first ∼500 cases of cervical intraepithelial neoplasia grade 3 (CIN3) or more severe disease (CIN3+) diagnosed at the study baseline. Methods Women aged 30 and older were screened for cervical cancer using Pap smears and tested for carcinogenic HPV using Hybrid Capture 2 (HC2; Qiagen). We randomly selected women who tested HPV positive and were diagnosed with CIN3+ (n = 448) or without CIN3+ (<CIN3) (n = 830). Residual specimens were HPV genotyped using a MY09/11 L1-targeted PCR method. Results Among HC2-positive women, HPV16 (48.9%), HPV31 (9.2%), and HPV18 (8.5%) were the most common HPV genotypes in CIN3+. There was a decrease at older ages in the fraction of CIN3 (ptrend = 0.006), adenocarcinoma in situ (AIS) (ptrend = 0.08), and CIN3/AIS (ptrend = 0.002) associated with HPV16. Compared to the other carcinogenic HPV genotypes in aggregate, HPV18 was strongly associated with CIN3+ in women with a normal Pap (odds ratio ([OR] = 5.7, 95%CI = 1.2-26) but not in women with abnormal Pap (OR = 1.3, 95%CI = 0.74-2.3). Conclusions HPV16 is associated with cervical precancer diagnosed in younger women (vs. older women). HPV18 infections were linked to precancerous lesions that were missed by cytology. Impact The progression timeline of HPV16 differs from other carcinogenic HPV genotypes, which may impact the use of HPV16 detection in the management of HPV-positive women.

HPV Type Attribution in High-Grade Cervical Lesions: Assessing the Potential Benefits of Vaccines in a Population-Based Evaluation in the United States

“…Our results show a clear predominance of HPV16/18 attribution in CIN2þ lesions among all women in every racial/ethnic group, in agreement with other studies (6,11,12,17,(23)(24)(25). However, we found that compared with non-Hispanic white women, HPV31/33/45/52/58 contributes to a significantly higher proportion of CIN2þ in racial minorities.…”

“…As expected, among the unvaccinated women, we found that HPV16/18 attribution was highest in the youngest age group and significantly decreased by age. The relatively lower proportions of HPV16/18-attributable lesions in the older group are congruent with epidemiologic evidence of stronger carcinogenic potential and faster progression of HPV16/ 18-associated lesions compared with lesions due to other highrisk types, and similar results have been shown in other studies (16,17,22,23).…”

A Study of Genotyping for Management of Human Papillomavirus-Positive, Cytology-Negative Cervical Screening Results

“…Starting in 2007, the PaP cohort was created by collecting residual cervical specimens in specimen transport medium (STM) (Qiagen) from a majority of women who tested positive with the Hybrid Capture 2 (HC2) (e.g., it was not possible to process specimens testing positive on Friday afternoons), as well as a random sample of HPV-negative specimens (which were not considered in the present study). After the specimens were used for HC2 testing for clinical purposes, the residual specimens were neutralized and archived, as described below (15).…”

“…Cases that were diagnosed directly following enrollment testing without an intervening second screen were considered prevalent. A random sample of HC2-positive women who had not been diagnosed as CIN2ϩ were chosen as prevalent controls, and all were typed by the laboratory of Robert Burk at the Albert Einstein College of Medicine in an extension of a previously reported prevalent case-control analysis (15). Cases that were diagnosed subsequent to enrollment (after a second screen) were considered incident and typed by Roche Molecular Systems at their research laboratory in Pleasanton, CA.…”

HPV16 genotype, p16/Ki‐67 dual staining and koilocytic morphology as potential predictors of the clinical outcome for cervical low‐grade squamous intraepithelial lesions

“…18,19 The distribution of HPV genotypes between different grades of cytological atypia suggests that the risk of progression could be associated with HPV genotype. [20][21][22] HPV genotypes 16 or 18 are more likely to have an underlying CIN2+ or to progress faster to high-grade squamous intraepithelial lesion (HSIL) compared with other genotypes. 23,24 The understanding of HPV infection and the pathogenesis of cervical intraepithelial lesions and cancer has led to the development of several molecular markers aimed at differentiating transient from transforming HPV infections.…”