Julia C. Gage

Association of HPV35 with cervical carcinogenesis among women of African ancestry: Evidence of viral‐host interaction with implications for disease intervention

AbstractHPV35 has been found in only ∼2% of invasive cervical cancers (ICC) worldwide but up to 10% in Sub‐Saharan Africa, warranting further investigation and consideration of impact on preventive strategies. We studied HPV35 and ethnicity, in relation to the known steps in cervical carcinogenesis, using multiple large epidemiologic studies in the U.S. and internationally. Combining five U.S. studies, we measured HPV35 positivity and, in Northern California, observed HPV35 type‐specific population prevalence and estimated 5‐year risk of developing precancer when HPV35‐positive. HPV35 genetic variation was examined for differences in carcinogenicity in 1053 HPV35+ cervical specimens from a U.S. cohort and an international collection. African‐American women had more HPV35 (12.1% vs 5.1%, P < .001) and more HPV35‐associated precancers (7.4% vs 2.1%, P < .001) compared to other ethnicities. Precancer risks after HPV35 infection did not vary by ethnicity (global P = .52). The HPV35 A2 sublineage showed an increased association with precancer/cancer in African‐Americans (OR = 5.6 vs A1, 95% CI = 1.3‐24.8) and A2 was more prevalent among ICC in Africa than other world regions (41.9% vs 10.4%, P < .01). Our analyses support a strong link between HPV35 and cervical carcinogenesis in women of African ancestry. Current HPV vaccines cover the majority of cervical precancer/cancer across all ethnic groups; additional analyses are required to determine whether the addition of HPV35 to the already highly effective nine‐valent HPV vaccine would provide better protection for women in Africa or of African ancestry.

Cervical Precancers and Cancers Attributed to HPV Types by Race and Ethnicity: Implications for Vaccination, Screening, and Management

AbstractBackgroundRacial and ethnic variations in attribution of cervical precancer and cancer to human papillomavirus (HPV) types may result in different HPV vaccine protection, screening test coverage, and clinical management.MethodsPooling data from 7 US studies, we calculated the proportional attribution of precancers and cancers to HPV types using HPV DNA typing from diagnosis. All statistical tests were 2-sided.ResultsFor all racial and ethnic groups, most cases of cervical intraepithelial neoplasia grade 3 (CIN3) (84.2%-90.8% of 5526) and squamous cell carcinoma (SCC) (90.4%-93.8% of 1138) were attributed to types targeted by the 9-valent vaccine. A higher proportion of CIN3s were attributed to nonvaccine HPV types among non-Hispanic Black women (15.8%) compared with non-Hispanic Asian or Pacific Islander (9.7%; P = .002), non-Hispanic White (9.2%; P < .001), and Hispanic (11.3%; P = .004) women. The proportion of SCCs attributed to 9-valent types was similar by race and ethnicity (P = .80). A higher proportion of CIN3s were attributed to nonvaccine HPV35 among non-Hispanic Black (9.0%) compared with non-Hispanic Asian or Pacific Islander (2.2%), non-Hispanic White (2.5%), and Hispanic (3.0%; all P < .001) women. Compared with CIN3, the proportion of SCCs attributed to HPV35 among non-Hispanic Black women (3.2%) was lower and closer to other groups (0.3%-2.1%; P = .70).ConclusionThe 9-valent HPV vaccine will prevent nearly all cervical precancers and invasive cancers among major racial and ethnic groups in the United States. Adding HPV35 to vaccines could prevent a small percentage of CIN3s and SCCs, with greater potential impact for CIN3s among Black women. HPV screening tests target high-risk HPV types, including HPV35. Future genotyping triage strategies could consider the importance of HPV35- and other HPV16-related types.

Long-term impact of cervical ablation in visual assessment of the squamocolumnar junction: implications for subsequent screening and follow-up

Cervical cancer screen-and-treat programs, which combine human papillomavirus (HPV)-based screening with immediate ablation of lesions, are a key strategy for reducing cervical cancer burden in low-resource settings. Although ablation is known to impair squamocolumnar junction (SCJ) visibility in the short-term, its long-term effects remain unclear, with potential implications for subsequent screening and follow-up. This study evaluated whether prior ablation is associated with incomplete SCJ visualization approximately 5 years post-treatment. We analyzed data from the Cervical Cancer Prevention in El Salvador program. Women aged 34 to 55 years who previously participated in Cervical Cancer Prevention in El Salvador were invited for HPV testing approximately 5 years after their initial screening. Those with positive results were further evaluated through visual inspection with acetic acid and colposcopy. We used generalized linear models to assess the association between prior ablation and incomplete SCJ visualization, adjusting for age, parity, and time since the initial HPV screen. Incomplete SCJ visualization was more frequent among women with prior ablation compared to those without previous treatment, both during colposcopy (47% vs 28%; OR 2.34, 95% CI 1.20 to 4.56) and visual inspection with acid (40% vs 25%; OR 2.06, 95% CI 1.05 to 4.01). Older age was also associated with impaired visualization, but the association between prior ablation and incomplete SCJ visibility remained significant after adjustment. Ablative treatment has a sustained impact on SCJ visualization that persists for years after the procedure, limiting the effectiveness of visualization-based surveillance. These findings underscore the need for efficient and affordable triage strategies to minimize unnecessary ablation in screen-and-treat programs and improve long-term follow-up care in low-resource settings.