Virus World

No cervical cancer cases were detected in Scotland in women born between 1988-1996 and fully vaccinated against HPV between ages 12 to 13, study says. A historic new study out of Scotland shows the real-world impact of vaccines against the human papillomavirus: The country has detected no cases of cervical cancer in women born between 1988-1996 who were fully vaccinated against HPV between the ages of 12 and 13. Many previous studies have shown that HPV vaccines are extremely effective in preventing cervical cancer. But the study, published on Monday in the Journal of the National Cancer Institute, is the first to monitor a national cohort of women over such a long time period and find no occurrence of cervical cancer.

“The study is super exciting. It shows that the vaccine is extremely effective,” said Kathleen Schmeler, a professor of gynecologic oncology at the University of Texas MD Anderson Cancer Center, who was not involved in the research. “It’s obviously early. We’re just starting to see the first data of the impact of the vaccine because it takes so long from the time of the vaccine to the effects.” The results underscore the importance of working to increase uptake of the HPV vaccine in the U.S., said Schmeler. Scotland, for example, introduced routine immunization in schools in 2008, and close to 90% of students in their fourth year of secondary school (equivalent to 10th grade in the U.S.) in the 2022-2023 school year had received at least one dose of the vaccine. In the U.S., where HPV vaccines are not administered in school, uptake among adolescents ages 13 to 17 is a little over 60%....

Study available here (jan. 22, 2024):

https://doi.org/10.1093/jnci/djad263

Experts said the figures show men are an 'important reservoi. r' for HPV, and should be included in control strategies. One in five men worldwide are infected with a potentially cancerous form of HPV, researchers have found. According to an analysis published in the Lancet Global Health journal, 21 per cent of men aged 15 and over are infected with at least one of the high-risk, potentially cancerous forms of HPV, or human papillomavirus – a family of more than 200 related viruses. In response to the findings, the World Health Organisation (WHO) said that more must be done to include men in global strategies to both reduce the risk for men and curb the spread of infection. While the majority of HPV cases are asymptomatic and resolve on their own, the virus can cause certain types of cancer, most commonly cervical – which kills around 340,000 women every year. But it is also linked to cancers of the genital areas and head, neck, throat and mouth – some of which affect men more than women and are becoming more common. In 2018, the International Agency for Research on Cancer estimated HPV was linked to more than 69,000 cancer cases in men. While HPV’s prevalence is fairly well-documented in women, estimates on its spread in men have been limited – until now.

HPV | The facts

It’s estimated that including boys in the HPV vaccination programme will prevent almost 50,000 non-cervical cancers by 2058, including 3,433 cases of penile cancer and 21,395 cases of head, neck and throat cancer in men. Vaccinated boys will also mean girls are doubly protected: “The girls’ programme has been very successful so far, and it’s already seen an impact in men as well as women,” says Dr Mary Ramsay, head of immunisation at Public Health England. “We’re hoping by adding boys to this it will accelerate the impact of the vaccination programme, bringing rates down even more quickly. I encourage all parents of eligible boys and girls to make sure they take up the offer for this potentially life-saving vaccine. It’s important not to delay vaccination, as the vaccine may be less effective as adolescents get older." When the jabs were first offered to girls in 2008, there was a catch up programme for older girls who had missed out, but this won’t be the case for boys. “Currently boys aged 13 to 18, who will have just missed out on the jab, won’t get a catch up programme like girls did in 2008, which is a decision Cancer Research UK is quite disappointed in,” says Sophia Lowes, health information manager at the charity. “However, parents can pay privately for their sons in that age group to have the vaccination. And it’s important to remember they have some protection, because most girls in that age group are vaccinated. After the age of 18 the vaccine is less effective, because you need it before you become sexually active and are exposed to HPV.”

After a systematic review which pooled data from more than 44,000 men across 65 previous studies, researchers estimated that one in three men globally are infected with genital HPV, while one in five had a “high risk”, potentially cancerous form. Infection rates overall were high among men aged 15-19 – suggesting they are being infected soon after their first sexual activity – but peaked among those aged 25-29. Rates remained high until the age of 50. This trend differs slightly from women, in which HPV rates decline with age, bar a slight spike during the menopause.

‘Important reservoir’

The new Lancet paper concluded that men are an “important reservoir of HPV genital infection”, and urged health authorities to consider targeting men with vaccinations, which are mainly used in women to prevent infection. Margaret Harris, a spokeswoman for the WHO, added: “The global study on HPV infection among men confirms how widespread HPV infection is in the sexually active population and affects not only women but also men. It also confirms the importance of introducing HPV vaccination in all countries and vaccines in the young population between 9 and 14 years of age before the HPV infection takes place.” The vaccine HPV is highly effective, having cut cervical cancer rates in England by 87 per cent since its nationwide rollout among teenage girls in 2008. In Britain, both girls and boys in year eight are routinely offered the vaccine, but across the world women have been prioritised in the rollout of inoculations. This is partly because there have been some shortages in supply. Ms Harris told the Telegraph that men are covered by “herd protection” when women are vaccinated, and said the latest study does not change the WHO’s advice to prioritise girls. But she added the paper reiterates that, where supply allows, men should be vaccinated and included in wider HPV control strategies. According to a 2022 WHO market analysis on the availability of HPV vaccines, there is now sufficient supply to inoculate two thirds of unvaccinated girls worldwide. “The market study also indicates that while in the short term adding secondary targets including older females and boys will have to be managed carefully, in the mid- and long term sufficient vaccines will be available for countries to add secondary targets such as boys if they can afford to do so,” Ms Harries added. 

Cited research published in The Lancet Global Health (Sept. 2023):

https://doi.org/10.1016/S2214-109X(23)00305-4 

Women carrying human papillomavirus (HPV) run an elevated risk of preterm birth, a University of Gothenburg study shows. A connection can thus be seen between the virus itself and the risk for preterm birth that previously has been observed in pregnant women who have undergone treatment for abnormal cell changes due to HPV.  A Swedish study now published in the high-ranking journal PLOS Medicine comprises data on more than a million births. Accordingly, the researchers have compared very large groups. They emphasize that the findings do not support any assessment of risk levels in individual women of childbearing age.

Johanna Wiik, a Ph.D. student in obstetrics and gynecology at Sahlgrenska Academy, University of Gothenburg, and also a gynecologist and obstetrician at the Department of obstetrics and gynecology at Sahlgrenska University Hospital, is the first author of the study. "I would like to point out that the increase in risk for preterm birth is small for the individual woman carrying HPV. But our results support that young people should get into the vaccination program against HPV," she says. Vaccination against HPV might not only prevent HPV related cancer but also be beneficial for pregnancy outcome.

Statistically significant increased risk

Treatment for abnormal cervical cell changes due to HPV infection had previously been known to increase risk of preterm birth—defined as birth before 37 weeks' gestation. The present study shows that HPV as such is linked to a raised risk of preterm birth, and of complications for the child. The study is based on birth particulars registered in the Swedish Medical Birth Register, which have been merged with the country's National Quality Registry for Cervical Cancer Prevention and the Swedish Cancer Register. Altogether, 1,044,023 births between 1999 and 2016 were included. Of the women concerned, 23,185 had previously received treatment, while 11,727 were untreated and had a positive HPV screening test immediately before or during their pregnancy. Of the women previously treated for CIN, 9.1 percent gave birth prematurely. The corresponding proportion in the group with HPV infection in conjunction with their pregnancies was 5.9 percent. This was a statistically significant increase compared with a reference group of women whose cervical screening test had always been normal, of whom 4.6 percent gave birth prematurely.

Importance of vaccines and cell sampling

Verena Sengpiel, Associate Professor of Obstetrics and Gynecology at Sahlgrenska Academy and obstetrician at Sahlgrenska University Hospital, is the study's last author. "Our study is register-based and, although we've adjusted for various factors in the analyses, we can't reliably answer the question of whether it's the virus itself that causes the pregnancy and childbirth complications. All we can do is show a statistical association," she says. "Soon we''ll be able to see how the incidence of preterm birth is affected after the vaccination program against HPV has been introduced. That will give us more information about whether there's a causal connection between HPV infection itself and delivery outcome." The researchers emphasize the importance of heeding calls for gynecological cell sampling, in order to detect any cervical cell changes due to HPV infection. Johanna Wiik again: "The earlier these abnormal cell changes are detected, the better we can follow and treat them. And when you're admitted to maternity care, it's a good idea to tell your midwife if you've had cervical cell changes, and whether you've been treated for them. Then the maternity health staff can take that information into account when planning the monitoring of your pregnancy."

The gene-editing tool CRISPR has been heralded as a scientific miracle destined to eradicate diseases from sickle-cell anemia to cancer, or decried as "the genetic scissors that tailor the human gene pool," an ethically risky technology driving us toward a designer babies.  Case Western Reserve University researchers see a different opportunity in the CRISPR technique: A new "universal biosensing" point-of-care medical device--similar to the existing commercial blood-glucose sensor--that rapidly and accurately detects troublesome viruses like human papillomavirus (HPV) or parvovirus B19 (PB-19).

To do that, researchers converted the CRISPR "recognition induced enzymatic signal" to an electrical signal, which was then used to detect the biomarkers for those viruses. Dai is the lead author on a paper about the process which landed the cover story for Angewandte Chemie, a journal of the German Chemical Society.  Dai said existing tests for those viruses take three to five days for an accurate result and can be expensive, while the biosensor envisioned by Case Western Reserve researchers would provide accurate results in under an hour.

According to the U.S. Centers for Disease Control, HPV is a common virus that can lead to six types of cancers later in life. Nearly 80 million Americans are infected with some type of HPV, spread through intimate skin-to-skin contact. Parvovirus B19, or parvo, spreads through respiratory secretions, such as saliva or nasal mucus, when an infected person coughs or sneezes. The virus can present a range of symptoms, depending on a person's age and overall health. About two out of 10 people infected with this virus will have no symptoms. Others may have only a mild rash..... E-CRISPR is the name Dai and co-authors gives to what they call an "electrochemical platform" that relies on the precision of the CRISPR technique to identify and quantify viruses in the blood. What sounds complex is actually quite simple, Dai said, "The CRISPR technique works so that it cuts all of the nonspecified single-strand DNA around it once the target is recognized, so we program to electrochemically probe this activity," he said. "No virus--no cutting, it's that simple. And the opposite is true: If CRISPR starts to cut, we know the virus is present."

Published in the J. Angewandte Chemie (September 30, 2019).:

https://doi.org/10.1002/anie.201910772

Human Papilloma Virus or HPV has been known to be transmitted between humans via sexual contact and HPV has been known to be a sexually transmitted disease or STD. The Centers for Disease Control and Prevention (CDC) states that HPV is one of the commonest STDs among humans. It affects around 79 million individuals in the United States. In most cases the infection may pass unnoticed and may resolve on its own. However HPV has been associated with the later development of cervival cancers in women and oral and throat cancers among men and women.

A new study however reveals that rabbit and mice papilloma viruses are capable of spreading via contaminated blood from one to another. The study from Pennsylvania State researchers titled, “Papillomavirus can be transmitted through the blood and produce infections in blood recipients: Evidence from two animal models” was published in the recent issue of the journal Emerging Microbes & Infections. The researchers warned that this study could be a basis for the hypothesis that HPV could also be transmitted between humans via blood.

Study leader Jiafen Hu, assistant professor of pathology and laboratory medicine at Penn State College of Medicine called for more research to confirm that papilloma viruses are capable of transmission via blood especially blood transfusions. He said that the blood prepared for receive blood transfusions may require a screening for HPV if this is proven to be true. Hu said, “People who are receiving blood transfusions typically have immune systems that aren't working optimally, so their systems are more vulnerable. We might want to think about adding HPV to the list of viruses for which blood donations are screened, as well as researching whether the typical viral load of HPV in human blood would be sufficient to cause infection.”

Hu explained that the team came across a case in 2005 where a similar transmission was seen. He said, “Some years ago, researchers were looking at blood samples from a group of HIV-positive children, and as they were testing those samples, they found that some of them were also positive for HPV. Because these children were so young, it prompted the question of whether the virus could have come from blood transfusions, which some of the children had undergone.”

Since it is difficult to check for HPV on animal models, the team decided to perform their experiments on other forms of papilloma viruses. “HPV is strictly species-specific,” they wrote, “and thus, cannot be studied directly in animals. Our laboratory has two preclinical animal models with their own naturally occurring papillomaviruses.”

The team used Cottontail Rabbit Papillomavirus which is commonly used for researching HPV infections in humans because of its similarity with HPV. For their experiments the team first injected the rabbit papilloma virus into the bloodstreams of the lab rabbits. The rabbits were then monitored for four weeks when they were found to develop tumours. This proved that the virus had travelled via the blood stream to cause the tumours in the rabbits said Hu. The team found that several genetic expressions were lower in these rabbit tumours similar to actual sexually transmitted tumours. They wrote, “The rabbit skin tumours induced via blood infection displayed decreased expression of SLN, TAC1, MYH8, PGAM2, and APOBEC2 and increased expression of SDRC7, KRT16, S100A9, IL36G, and FABP9, as seen in tumours induced by local infections.”

Hu explained that in this experiment they had used a large amount of the virus to be injected into the rabbits. This infection due to the injection of the viruses could be due to the heavy viral load, he added. In a normal case of blood borne infection, the dose of the virus could be significantly lower. Thereafter the team reduced the viral load injected by five times. This time the tumours were still seen in 18 out of the 32 animals. Hu said, “We were able to show that the virus in the blood caused tumors, but what about blood transfusions? People receiving a transfusion may only get a very small amount of the virus. To simulate this, we injected the virus into one animal, took 10 millilitres of blood and transfused it into a second animal. We still saw tumors.”

The next question the researchers addressed was if the blood borne infection could cause tumours and cancerous changes in the cervix as the sexually transmitted infection was capable of. Now they repeated their experiment using mice model. When injected with the papilloma virus into lab mice, the team found that the virus and viral warts and tumours were found in the tongue and genital mucosa of the mice. They also found the virus in the stomach mucosa of the mice. This proved that the virus was capable of travelling from the blood stream into oral and genital mucosa as well as into the gastric mucosal surfaces.

Findings published in the Journal of Emerging Microbes and Infections:

https://doi.org/10.1080/22221751.2019.1637072

In a recent study published in the journal Scientific Reports, researchers used a nationwide case-control study of Taiwanese residents to investigate the association between human papillomavirus (HPV) and thyroid cancer. Analyses of the 3,062 thyroid cancer patients and 9,186 healthy controls revealed that individuals with a prior HPV infection had more than double the likelihood of developing thyroid cancer than those without the infection (odds ratios 2.199 for HPV patients). This research presents the first concrete evidence of a carcinogen for thyroid cancer, the most common endocrine cancer and a growing concern worldwide.

The first generation HPV vaccine cut cervical cancer rates among women by 87%, British researchers reported.  The study published Wednesday in the journal The Lancet estimates that by mid-2019, there were 450 fewer cases of cervical cancer and 17,200 fewer cases of pre-cancers than expected in the vaccinated population. Researchers at Kings College London and the British government looked at population-based cancer registry data in the UK between January 2006 and June 2019 for seven groups of women, comparing those who were vaccinated to those who were not. They were looking at data covering the Cervarix vaccine, which protects against two strains of cancer-causing human papillomavirus or HPV. Newer vaccines sold under the Gardasil brand protect against even more strains of cancer causing viruses.  Of the three groups that were vaccinated, each were vaccinated at different ages. One group was vaccinated at age 12-13, another at 14-16, and another at 16 -18. Those vaccinated at the earliest ages were the most protected, the team reported. Those who got the shot between the ages of 14 and 16 saw an 62% reduced rate, and rates were reduced by 24% among those vaccinated between 16 and 18. "This study provides the first direct evidence of the impact of the UK HPV vaccination campaign on cervical cancer incidence, showing a large reduction in cervical cancer rates in vaccinated cohorts," study co-author Dr. Kate Soldan from the UK Health Security Agency said.

Human papillomavirus infection may increase the risk of breast carcinoma: a large-scale systemic review and meta-analysis of case-control studies found.

Breast carcinoma (BC) is a cancer with a high morbidity rate, but the mechanisms by which it develops are not completely understood. There has been speculation regarding the potential association between breast cancer and local HPV infections. Although much clinical research supports this hypothesis, some research results disprove the association. The association of HPV infection and BC was put forward by Band et al. in 1990. Band et al. reported that HPV could immortalize normal human mammary epithelial cells, and reduce their requirement on growth factors. Since 1992, an increasing number of researches have investigated the relationship between HPV infection and BC. However, the conclusions of these studies were controversial.

Here, we analyzed 37 case control studies containing 3,607 BC cases and 1,728 controls showed an increase of BC risk with human papillomavirus (HPV) positive [summary odds ratio (SOR) =6.22, 95% confidence interval 4.25 to 9.12; P=0.0002]. Subgroup analysis proved three high risk HPV types (HPV16, 18 and 33) were positively correlated to BC. As to the potential mechanism, association between HPV and BC has not been confirmed yet. We have to admit that the appearance of HPV is not sufficient to prove virus’ etiological role in BC development. 

Our meta-analysis has certain limitations. For instance, most studies included here were conducted in Asian countries. As is reported by Li et al. (49), although 32.42% of BC cases were HPV-associated in Asians, only 12.91% were in Europeans. Also, the histology types were obliged to be analyzed by subgroup. However, due to the lack of specified data on the clinical trials, we cannot perform them in this article. Thus, these limitations are likely to introduce bias. This systemic review and meta-analysis provide the evidence for HPV infection as a potential risk factor in BC, while the mechanism still needs further evaluation.

Published in Gland Surgery (October 2019) - Open access:

https://doi.org/10.21037/gs.2019.09.04

The HPV vaccine is one of only two vaccines that prevent cancer but is underutilized in the United States. Despite its proven success at preventing cancer, many adolescents are still not getting the HPV vaccine. A new study from the University of Colorado School of Medicine at the Anschutz Medical Campus shows that physicians’ delivery and communication practices must improve to boost vaccination completion rates. Health care providers must also learn to deal with parents hesitant to get their children vaccinated with HPV vaccine.

The study, to be published tomorrow (September 16, 2019) in Pediatrics, is the first to examine pediatricians and family physicians’ delivery practices for the vaccine since the new 2-dose schedule came out for adolescents 11 or 12-years-old. “A physician recommendation is one of the most important factors in vaccine acceptance by parents,” said Allison Kempe, MD, MPH, lead author and professor of pediatrics at the University of Colorado School of Medicine. “However, we’re seeing a lack of understanding from healthcare providers about the need for vaccination early in adolescence and high rates of refusal on the part of parents. The vaccine is underutilized, with less than half of American adolescents completing the vaccination. We need to maximize methods of introducing the vaccine that we know to be more effective, as well as the use of reminder and delivery methods at the practice in order to improve this rate.”

Every year, HPV causes over 33,500 cases of cancer in women and men in the United States, according to the Centers for Disease Control and Prevention.

“The earlier someone is vaccinated, the better the immune system responds. It also increases the chances of being vaccinated before having exposure to HPV strains,” Kempe said. “If we can increase the rate of vaccination in early adolescence, then we can prevent cancers that develop in later years.”

The study surveyed 588 pediatricians and family physicians and found that refusal rates from parents remain high, especially for 11 to 12-year-olds, the target population for vaccination. But physicians who use a `presumptive style’ approach have higher acceptance rates. Presumptive style means physicians introduce the HPV vaccine and recommend it in the same manner and as strongly as the other recommended adolescent vaccines for meningitis and Tdap. For example, a doctor could say, “We’ve got three vaccines today: Tdap, HPV and Meningitis,” rather than isolating HPV as an option that is not as important.

Still, the survey found some encouraging signs:

• Despite a high refusal rate, pediatricians who strongly recommend the vaccine increased from 60% in 2013 to 85% in 2018 for 11 or 12-year-old females and from 52% to 83% for 11 to 12-year-old males.
• Some 89% of pediatricians and 79% of family pediatricians reported more adolescents under age 15 are completing the HPV series now that only 2 doses are recommended.

Along with improving physician communication styles, HPV delivery could also be optimized by increased use of standing orders and alert systems in the medical record to remind providers of the need for vaccination at the point of care.

Study published on Sept. 16 in the jopurnal Pediatrics:

https://doi.org/10.1542/peds.2019-1475

More than 100,000 cases of cancer will be prevented under plans to give boys the HPV jab as well as girls, UK health officials have said. 

Giving boys the vaccine protects girls from the human papilloma virus (HPV), which is passed on through sexual contact. And it will also protect them from a range of other forms of the disease, including some cancers of the head and neck, and penile, anal and genital cancers. Scientists hope that cervical cancer could be eradicated within decades, because of the success of the jabs. Since the vaccine was introduced for teenage girls in 2008, cases of HPV have fallen by 86 per cent among the age groups vaccinated.

Professor Beate Kampmann, director of the vaccine centre at the London School of Hygiene and Tropical Medicine, said: "This decision is a triumph for gender equality in cancer prevention.

"It's pleasing to see the UK follow the example of other countries like Australia, where the vaccine has been implemented for girls since 2007 and for boys since 2013."

Estimates from the University of Warwick suggest the vaccine will prevent 64,138 cervical cancers and 49,649 non-cervical cancers in the UK by 2058.  This will include 3,433 cases of penile cancer and 21,395 cases of head and neck cancer, such as throat cancer, in men.

UK Health report available at:

 https://www.gov.uk/government/organisations/public-health-england