Hepatitis B Virus Associated With Cervical Cancer, Not Ovarian or Endometrial Cancers

Hepatitis B virus (HBV) is positively correlated with cervical cancer but not with ovarian or endometrial cancers, according to a study published in Discover Oncology.¹

Gynecologic cancer is a growing health challenge worldwide, with cervical cancer being the most common type.² Also, gynecologic cancer–related mortality rates remain high despite updated screening, diagnosis, and treatment methods. For example, annually, about 20,000 US women are diagnosed with ovarian cancer, and 13,000 die from it.³

The researchers explained that HBV is considered one of the main active causes of hepatocellular carcinoma as recent studies have associated it with increasing extrahepatic malignancy risk, like gastric and pancreatic cancers.⁴ Also, HB surface antigen (HBsAG), core antigen (HBcAG), and DNA can be detected in the ovaries, uterus, and vaginal secretion¹; evidence suggests that HBV can be sexually transmitted, like human papillomavirus (HPV).

However, current research remains divided on the relationship between HBV infection and malignant gynecologic tumor risk. Some studies have shown that HBV infection is a risk factor for endometrial, cervical, and ovarian cancers, but others did not demonstrate any correlation between them.

Consequently, they further investigated the potential relationship between HBV infection and the risk of gynecological malignancies, namely cervical, endometrial, and ovarian cancers. Through a meta-analysis, the researchers assessed the strength of the association between HBV infection and malignant gynecologic tumor risk in women. They also conducted subgroup analyses, primarily based on population source (population based vs hospital based), study design (case-control vs cohort), and ethnicity (Asian vs non-Asian).

Hepatitis B virus (HBV) is associated with an increased risk of cervical cancer but not with ovarian or endometrial cancers. | Image Credit: Destina - stock.adobe.com

The researchers searched for eligible studies on PubMed, Cochrane Library, and Embase from database inception to December 31, 2022, using relevant keywords. They also manually scanned the reference lists of retrieved articles to ensure all eligible studies were reviewed. Conversely, the researchers excluded studies that were not fully accessible or did not present the primary data. They also excluded reviews, case reports, comments, and conference abstracts.

Using the Newcastle-Ottawa scale (NOS), the researchers evaluated the quality of the included articles based on study group selection, group comparability, and exposure/outcome determination; the maximum score was 9 points, with more points indicating a higher-quality study. The researchers extracted various data from the studies, including the study design, cancer type, and sample size.

Initially, they identified 775 eligible studies. After multiple elimination rounds, 7 studies remained, consisting of 5 case-control studies (83,643 cases; 156,786 controls) and 2 cohort studies (1362 gynecologic malignancy cases out of 335,088 subjects) published between 2014 and 2022. Besides 1 from the US, all included studies were from Asia (1 from South Korea, 5 from China).

The researchers noted that population-based and hospital-based studies each accounted for about half of the total. Additionally, each study’s NOS quality score ranged from 6 to 9, indicating high quality.

Four case-control and 2 cohort studies analyzed cervical cancer risk in patients who were HBsAG-positive. The researchers determined that cervical cancer was significantly associated with HBV infection (OR, 1.22; 95% CI, 1.09-1.38; P = .001). Also, the subgroup analysis by study design determined that HBV infection was positively correlated with cervical cancer risk in case-control studies (OR, 1.27; 95% CI, 1.13-1.44; P = .000), but this trend was not found in cohort studies (OR, 0.77; 95% CI, 0.51-1.17; P = .219).

Similarly, the pooled estimate risk in hospital-based studies (OR, 1.30; 95% CI, 1.14-1.47; P = .000) was higher than that in population-based studies (OR, 0.94; 95% CI, 0.71-1.24; P = .661). However, through the subgroup analysis by ethnicity, only Asian women with HBV (OR, 1.24; 95% CI, 1.10-1.40; P = .001) were associated with an increased cervical cancer risk.

Also, the researchers identified 4 case-control and 2 cohort studies that analyzed the relationship between HBV infection and endometrial cancer risk. Of the studies, only 2 showed an increased endometrial cancer risk in patients with HBV infection (OR, 2.32; 95% CI, 1.53-3.51; OR, 1.69; 95% CI, 1.09-2.61).

Through the subgroup analyses, they found no association between HBV infection and endometrial cancer risk in either the cohort (OR, 1.16; 95% CI, 0.72-1.87; P = .554) or case-control (OR, 1.35; 95% CI, 0.92-2.01; P = .129) studies. Conversely, HBV infection was associated with increasing endometrial cancer risk in hospital-based populations (OR, 1.61; 95% CI, 1.04-2.49; P = .032) and female Asian patients (OR, 1.46; 95% CI, 1.07-1.99; P = .026).

Lastly, 5 studies analyzed the association between HBV infection and ovarian cancer risk. Of these studies, only 1 showed a causal relationship (OR, 2.31; 95% CI, 1.21-4.39). Conversely, the subgroup analyses indicated that HBV infection did not increase ovarian cancer risk.

The researchers acknowledged their limitations, one being that the meta-analysis mostly included case-control studies; these studies are more prone to recall or selection bias. Also, the meta-analysis was mostly based on East Asian populations, which have high chronic HBV infection rates. Therefore, their findings may not be generalizable to those in other regions. However, the researchers expressed confidence in their findings and suggested areas for further research.

“These results provide a foundation for better prevention and treatment of gynecologic malignancies, which is of significance to clinical and public health,” the authors concluded. “Considering the limitations of existing studies, more multicenter studies are needed to confirm the findings.”

References

1. Peng L, Dou Z, Yu S, et al. Hepatitis B virus infection and the risk of gynecologic cancers: a systematic review and meta-analysis. Discov Oncol. 2024;15(1):340. doi:10.1007/s12672-024-01213-8
2. Sung H, Ferlay J, Siegel RL, et al. Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2021;71(3):209-249. doi:10.3322/caac.21660
3. Siegel RL, Miller KD, Wagle NS, Jemal A. Cancer statistics, 2023. CA Cancer J Clin. 2023;73(1):17-48. doi:10.3322/caac.21763
4. Hassan MM, Hwang LY, Hatten CJ, et al. Risk factors for hepatocellular carcinoma: Synergism of alcohol with viral hepatitis and diabetes mellitus. Hepatology. 2002;36(5):1206-1213. doi:10.1053/jhep.2002.36780