DESIGN: Systematic literature review.
DATA SOURCES: Seven databases were searched from inception to 31 August 2020. A focused search was performed to supplement the results.
ELIGIBILITY CRITERIA: Studies which reported either healthcare resource utilisation or costs associated with HSV-related healthcare, including screening, diagnosis and treatment of genital HSV infection and neonatal herpes prevention and treatment.
DATA EXTRACTION AND SYNTHESIS: Two independent reviewers extracted data and assessed the risk of bias using the Larg and Moss's checklist. All data were summarised narratively.
RESULTS: Out of 11 443 articles, 38 were included. Most studies (35/38, 94.6%) were conducted in high-income countries, primarily the United States, and were more often related to the prevention or management of neonatal herpes (n=21) than HSV genital ulcer disease (n=17). Most analyses were conducted before 2010. There was substantial heterogeneity in the reporting of HSV-related healthcare resource utilisation, with 74%-93% individuals who sought care for HSV, 11.6%-68.4% individuals who received care, while neonates with herpes required a median of 6-34 hospitalisation days. The costs reported were similarly heterogeneous, with wide variation in methodology, assumptions and outcome measures between studies. Cost for screening ranged from US$7-100, treatment ranged from US$0.53-35 for an episodic therapy, US$240-2580 yearly for suppressive therapy, while hospitalisation for neonatal care ranged from US$5321-32 683.
CONCLUSIONS: A paucity of evidence exists on healthcare resource utilisation and costs associated with HSV infection, especially among low-income and middle-income countries. Future research is needed on costs and healthcare utilisation patterns to improve overall understanding of the global economic burden of HSV.
METHODS AND FINDINGS: We followed a cohort of 308,036 women recruited in the European Prospective Investigation into Cancer and Nutrition (EPIC) Study. At enrollment, participants completed a questionnaire and provided serum. After a 9-year median follow-up, 261 ICC and 804 CIN3/CIS cases were reported. In a nested case-control study, the sera from 609 cases and 1,218 matched controls were tested for L1 antibodies against HPV types 11,16,18,31,33,35,45,52,58, and antibodies against Chlamydia trachomatis and Human herpesvirus 2. Multivariate analyses were performed to estimate hazard ratios (HR), odds ratios (OR) and corresponding 95% confidence intervals (CI). The cohort analysis showed that number of full-term pregnancies was positively associated with CIN3/CIS risk (p-trend = 0.03). Duration of oral contraceptives use was associated with a significantly increased risk of both CIN3/CIS and ICC (HR = 1.6 and HR = 1.8 respectively for ≥ 15 years versus never use). Ever use of menopausal hormone therapy was associated with a reduced risk of ICC (HR = 0.5, 95%CI: 0.4-0.8). A non-significant reduced risk of ICC with ever use of intrauterine devices (IUD) was found in the nested case-control analysis (OR = 0.6). Analyses restricted to all cases and HPV seropositive controls yielded similar results, revealing a significant inverse association with IUD for combined CIN3/CIS and ICC (OR = 0.7).
CONCLUSIONS: Even though HPV is the necessary cause of CC, our results suggest that several hormonal factors are risk factors for cervical carcinogenesis. Adherence to current cervical cancer screening guidelines should minimize the increased risk of CC associated with these hormonal risk factors.