Therapeutic DNA Vaccines against HPV-Related Malignancies: Promising Leads from Clinical Trials.

In 2014 and 2021, two nucleic-acid vaccine candidates named MAV E2 and VGX-3100 completed phase III clinical trials in Mexico and U.S., respectively, for patients with human papillomavirus (HPV)-related, high-grade squamous intraepithelial lesions (HSIL). These well-tolerated but still unlicensed vaccines encode distinct HPV antigens (E2 versus E6+E7) to elicit cell-mediated immune responses; their clinical efficacy, as measured by HSIL regression or cure, was modest when compared with placebo or surgery (conization), but both proved highly effective in clearing HPV infection, which should help further optimize strategies for enhancing vaccine immunogenicity, toward an ultimate goal of preventing malignancies in millions of patients who are living with persistent, oncogenic HPV infection but are not expected to benefit from current, prophylactic vaccines. The major roadblocks to a highly efficacious and practical product remain challenging and can be classified into five categories: (i) getting the vaccines into the right cells for efficient expression and presentation of HPV antigens (fusion proteins or epitopes); (ii) having adequate coverage of oncogenic HPV types, beyond the current focus on HPV-16 and -18; (iii) directing immune protection to various epithelial niches, especially anogenital mucosa and upper aerodigestive tract where HPV-transformed cells wreak havoc; (iv) establishing the time window and vaccination regimen, including dosage, interval and even combination therapy, for achieving maximum efficacy; and (v) validating therapeutic efficacy in patients with poor prognosis because of advanced, recurrent or non-resectable malignancies. Overall, the room for improvements is still large enough that continuing efforts for research and development will very likely extend into the next decade.

Hispanic Ethnicity and Cervical Cancer Precursors Among Low-Income Women in Arizona.

PURPOSE: In the United States, Hispanics are more likely to be diagnosed with cervical cancer compared to Non-Hispanic Whites. Annually, 250,000 to 1 million women are diagnosed with a precursor to CC. The aim of this study was to assess whether Hispanics have a higher prevalence of cervical dysplasia compared to Non-Hispanics Whites among a population of low-income women. PATIENTS AND METHODS: We analyzed the results of 10,911 cervical cytology tests administered between 2003 and 2016 that were funded through the Center for Disease Control and Prevention's (CDC) program for low-income, uninsured women entitled the National Breast and Cervical Cancer Early Detection Program (NBCCEDP). In the state of Arizona, the program is called the Well Women HealthCheck Program (WWHP). Logistic regression was used to identify increased risk of dysplasia, including low-grade squamous intraepithelial lesions (LSIL) and high-grade squamous intraepithelial lesions (HSIL/ICC), and multinomial logistic regression was used to assess increased likelihood for LSIL and HSIL/ICC as separate categories. RESULTS: In the crude analysis, Hispanic ethnicity was modestly associated with higher prevalence of LSIL (odds ratio (OR)=1.39, 95% CI=1.01-1.91), but this association was not statistically significant after adjusting for confounders. However, in the final models, lower income was independently associated with LSIL (adjusted odds ratio [aOR]=1.55, 95% CI=1.30-1.44), while smoking (aOR=2.88, 95% CI=1.21-6.84) and no history of Pap test within five years (aOR=3.54, 95% CI=1.61-6.99) were independently associated with HSIL. CONCLUSION: After adjusting for confounding in a sample of low-income women with comparable Pap screening rates, ethnicity was not associated with greater prevalence of abnormal pap smears. However, other variables were independently associated with LSIL and HSIL. The higher proportion of LSIL cases among lower income individuals compared to those with higher incomes, and the higher proportion of HSIL cases observed among those screened least regularly stresses the importance of programs like WWHP: programs that target low-income, uninsured women. These programs help save lives.