Human papillomavirus (HPV) genotypes in women with cervical precancer and cancer at Kaiser Permanente Northern California.

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. 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 cervical Pap specimens were HPV genotyped using a MY09/11 L1-targeted PCR method. 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 (P(trend) = 0.006), adenocarcinoma in situ (AIS) (P(trend) = 0.08), and CIN3/AIS (P(trend) = 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). HPV16 is more strongly associated with cervical precancer diagnosed in younger women (vs. older women). HPV18 infections were linked to precancerous lesions that were missed by cytology. 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.

Castle PE ，Shaber R ，LaMere BJ ，Kinney W ，Fetterma B ，Poitras N ，Lorey T ，Schiffman M ，Dunne A ，Ostolaza JM ，McKinney S ，Burk RD ... -  《-》

The elevated 10-year risk of cervical precancer and cancer in women with human papillomavirus (HPV) type 16 or 18 and the possible utility of type-specific HPV testing in clinical practice.

Khan MJ ，Castle PE ，Lorincz AT ，Wacholder S ，Sherman M ，Scott DR ，Rush BB ，Glass AG ，Schiffman M ... -  《-》

Human papillomavirus genotypes in cervical intraepithelial neoplasia grade 3.

Castle PE ，Schiffman M ，Wheeler CM ，Wentzensen N ，Gravitt PE ... -  《-》

Calendar-period trends in cervical precancer and cancer diagnoses since the introduction of human papillomavirus and cytology co-testing into routine cervical cancer screening at Kaiser Permanente Northern California.

The longer-term impact of introducing human papillomavirus (HPV) testing into routine cervical cancer screening on precancer and cancer rates by histologic type has not been well described. Calendar trends in diagnoses were examined using data from Kaiser Permanente Northern California, which introduced triennial HPV and cytology co-testing in 2003 for women aged ≥30 years. We examined trends in cervical precancer (cervical intraepithelial neoplasia grade 3 [CIN3] and adenocarcinoma in situ [AIS]) and cancer (squamous cell carcinoma [SCC] and adenocarcinoma [ADC]) diagnoses per 1000 screened during 2003-2018. We examined ratios of squamous vs. glandular diagnoses (SCC:ADC and CIN3:AIS). CIN3 and AIS diagnoses increased approximately 2% and 3% annually, respectively (ptrend < 0.001 for both). While SCC diagnoses decreased by 5% per annually (ptrend < 0.001), ADC diagnoses did not change. These patterns were generally observed within each age group (30-39, 40-49, and 50-64 years). ADC diagnoses per 1000 screened did not change even among those who underwent co-testing starting in 2003-2006. SCC:ADC decreased from approximately 2.5:1 in 2003-2006 to 1.3:1 in 2015-2018 while the CIN3:AIS remained relatively constant, ∼10:1. Since its introduction at KPNC, co-testing increased the detection of CIN3 over time, which likely caused a subsequent reduction of SCC. However, there has been no observed decrease in ADC. One possible explanation for lack of effectiveness against ADC is the underdiagnosis of AIS. Novel strategies to identify and treat women at high risk of ADC need to be developed and clinically validated.

Befano B ，Wentzensen N ，Lorey T ，Poitras N ，Cheung LC ，Schiffman M ，Clarke MA ，Cohen C ，Kinney W ，Locke A ，Castle PE ... -  《-》

Human papillomavirus type 16 infections and 2-year absolute risk of cervical precancer in women with equivocal or mild cytologic abnormalities.

Castle PE ，Solomon D ，Schiffman M ，Wheeler CM ... -  《-》