Human papillomavirus (HPV) continues to be a hot topic to laboratory scientists, to clinical practitioners, and to the general public. The relationship between HPV and cervical and other cancers, advancements in diagnostics and screening, and issues related to vaccination are frequent areas of study by researchers. Here are summaries of three recent HPV studies that could have far-reaching significance.
HPV vaccine and improved fertility
More than 40 percent of American teens are now getting vaccinated against human papillomavirus. But, despite HPV infection being associated with reduced semen quality and lower pregnancy rates, there is still public concern about whether the HPV vaccine itself could affect future fertility.
Now, the first prospective cohort examining the relationship between HPV vaccination and fertility, led by a Boston University School of Public Health (BUSPH) researcher, has found that the vaccine can actually improve chances of conception in some women.
The study, published in the journal Paediatric and Perinatal Epidemiology, shows little overall association between HPV vaccination and the chances of conceiving for men and women—except among women with a history of sexually transmitted infections (STIs). STIs are associated with lower fertility, but vaccinated women with an STI history had about the same chance of becoming pregnant as unvaccinated women who had never had an STI.
“Our study found no adverse effects of HPV vaccination on fertility and indicated that it may, in fact, protect fertility among individuals who have had other STIs,” says BUSPH doctoral student Kathryn McInerney, the study’s lead author. “Our study should reassure those who are hesitant to vaccinate due to fertility concerns.”
The study used data derived from the Pregnancy Study Online (PRESTO), a preconception cohort of North American pregnancy planners. The ongoing study enrolled 3,483 women and 1,022 men aged 21 to 45 years who were actively trying to conceive. Couples were followed for 12 months or until pregnancy, whichever came first. At enrollment, 33.9 percent of women had been vaccinated against HPV, compared to 5.2 percent of men.
“Internationally, parents have chosen not to vaccinate their children due to concerns about the vaccine’s effect on future fertility,” McInerney says. “We hope this study will be useful for health providers who counsel individuals and families about HPV vaccination.”
Screening for cervical abnormalities
HPV testing detects a higher number of precancerous cervical lesions than cytology-based Pap smears in a female population including a proportion offered HPV vaccination, according to a new study conducted by Australian researchers and published in PLOS Medicine.
Many countries are currently considering switching from classic Pap tests to primary HPV tests for cervical cancer screening, based on strong evidence linking cervical abnormalities and infection with certain HPV types and data suggesting that HPV tests detect more high-grade precancerous lesions. However, no study has yet compared the different methods in a population in which younger women had been offered prior HPV vaccination.
In the new study, researchers randomized cervical samples from 4,995 women aged 25 to 64 in Australia, in a 1:2:2 ratio, to be analyzed by either cytology (with HPV testing of low-grade abnormalities); HPV testing with partial genotyping of the virus for the highest-risk types HPV16 and 18, and cytology (for participants with other high-risk HPV genotypes); or HPV testing with partial genotyping and dual-stained cytology. In the first screening round of the trial, the authors assessed the rates of women being referred for further testing and of detection of CIN2+ (high-grade cervical intraepithelial neoplasia) precancerous lesions.
For the cytology group, the overall referral and detected CIN2+ rates were 27/995 (2.7 percent and 1/995 (0.1 percent); for the HPV testing and cytology group, they were 75/1992 (3.8 percent) and 20/1992 (1.0 percent); and for the HPV and dual-stained cytology group, they were 79/2008 (3.9 percent) and 24/2008 (1.2 percent). The researchers found that, in the first round of screening, detection of CIN2+ was significantly increased with HPV testing as compared with cytology, while referral was non-significantly increased. Adverse events were rare, and the one case of early-stage cervical cancer (in the HPV testing plus cytology group) was detected as appropriate by screening.
“These findings provide initial confirmation of an improved performance of primary HPV screening compared to cytology screening in settings with HPV-vaccinated populations,” says lead author Karen Canfell, PhD, of Cancer Council New South Wales, Australia. These findings support the planned introduction of cervical screening by HPV testing in Australia, which will occur at the end of 2017.
HPV testing and cervical pre-cancer
Women who receive human papillomavirus (HPV) testing in addition to a pap smear receive a faster, more complete diagnosis of possible cervical precancer, according to a study of more than 450,000 women by Queen Mary University of London (QMUL) and the University of New Mexico Comprehensive Cancer Center.
The study, published in JAMA Oncology, used data from the New Mexico HPV Pap Registry in the United States. It is the first comprehensive evaluation of HPV testing on the long-term outcomes of women who had received a borderline abnormal Pap test result.
A total of 457,317 women were included in the study. Of these, 20,677 women (4.5 percent) received a borderline abnormal result through a Pap smear and were followed in the study for five years. Some of the women with borderline abnormal Pap smear results had an HPV test.
HPV testing led to a 15.8 percent overall increase in the detection of cervical precancers, and time to detection was much shorter (a median of 103 days versus 393 days).
Virtually all cervical pre-cancers were detected in women who tested positive for HPV, suggesting HPV testing is a good additional screening method after the Pap smear. Colposcopy (a medical examination of the cervix) could then be focused on women who would need it most: those with a positive HPV test.
At the same time, however, HPV testing of women resulted in 56 percent more biopsies and a 20 percent increase in surgical treatment procedures performed. Most of the additional biopsies were for low-grade lesions which could have regressed, indicating some overtreatment due to HPV testing.
Professor Jack Cuzick from QMUL says: “This study shows that knowing a woman’s HPV status can help determine her likelihood of needing additional procedures, and prioritize immediate treatment and medical resources to the women who need them most.”
The authors warn that, as this was an observational study, the use of HPV testing was not randomized. Thus there could have been socioeconomic or other relevant differences among healthcare facilities that have not been measured.