HPV Subtypes Linked to Development of High-Grade Cervical Cancer

Sonia Andersson, MD, PhD

The presence of specific subtypes of HPV, namely HPV-16 and -18, were found to be associated with a higher risk of developing high-grade cervical intraepithelial neoplasia (CIN) in women under the age of 30, according to results of a nested case-control Swedish study published in Cancer.

“These findings can help in the ongoing development of guidelines for cervical cancer screening,” said principal investigator Sonia Andersson, MD, PhD, of the Karolinska University Hospital and Institute in Sweden. “They strongly indicate that testing for HPV needs to be incorporated into screening programs.”

Screening for cervical cancer is becomingly increasingly reliant on HPV status. As such, this study examined the impact of baseline HPV status on the future risk of developing grade ≥2 CIN. Baseline HPV status was determined with liquid-based cytology samples.

Women who had participated in the Swedish cervical screening program between 2005 and 2007 who tested negative for intraepithelial lesions or malignancy at baseline and developed grade ≥2 CIN in the 9 years of follow-up were included in the nested study.

Of the 9047 women who tested negative for CIN at baseline, 96 cases were extracted for evaluation. Patients were excluded if they had prior ≥2 CIN, negative baseline with koilocytosis or insufficient material, endometrial adenocarcinoma, or a missing sample or lack of material in the sample container. The 96 remaining patients went on to have a histologically confirmed diagnosis of grade 2 or 3 CIN, adenocarcinoma in situ, or cervical cancer during the follow-up period.

Data pulled from the Swedish registry system enabled case controls to be matched 5:1 based on age (±365 days), baseline screening date (±180 days), and screening history prior to and following baseline (0 versus 1 or more screening cytologies). The women who served as case controls tested negative for a cytological or histopathological diagnosis of ≥2 CIN throughout follow-up. The 9-year follow-up data on cervical cytology and histopathology were pulled from the National Cervical Screening Registry.

Results demonstrated that the risk of developing high-grade CIN strongly correlated with a woman’s baseline HPV status. Among the study population, HPV status was tested with the RealTime High-Risk HPV assay, accounting for 14 HPV types: 16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 66, and 68.

In women under the age of 30, HPV-16 and HPV-18 demonstrated a strong correlation with future risk for ≥2 CIN (odds ratio, 9.44; 95% CI, 3.37-26.4). No other HPV types were linked with subsequent development of disease in this subpopulation, whereas women age 30 and older were at increased risk regardless of HPV type.

Over the course of follow-up, 44 women (45.8%) were diagnosed with grade 2 CIN. Fifty-two (54.2%) women were diagnosed with ≥3 CIN, of which 7 were adenocarcinoma in situ, 3 were squamous cell carcinoma, and 1 was adenocarcinoma.

The detection of HPV did not seem to depend on the grade of CIN, though HPV-16 and HPV-18 were more commonly detected among patients who developed ≥3 CIN versus those who developed grade 2 CIN (Pearson χ2, 6.12; 2-sided P <.02).

“Women younger than 30 with a positive HPV-16 or HPV-18 finding need to be closely followed, whereas other HPV types are much less likely to be associated with increased risk in these younger women,” concluded Andersson. “Among women above age 30, any HPV-positive finding should be closely followed.”

Fröberg M, Östensson E, Belkic&#769; K, et al. The impact of HPV status on development of high-grade cervical intraepithelial neoplasia in women negative for intraepithelial lesions or malignancy at baseline: 9-year Swedish nested case-control follow-up study [published online December 10, 2018]. Cancer. doi: 10.1002/cncr.31788.