Screening HPV infection alone more accurate than Pap test in detection of cervical cancer

Screening for human papillomavirus (HPV) infection alone gives more accurate results than Pap (smear) testing for cervical cancer, say the authors of two papers to published today in the journal Gynecologic Oncology. HPV infection causes almost all cervical cancer, and it is estimated that more than half of sexually active people are infected with HPV at some point in their lives. Now new research has shown that in many cases, an HPV test alone can be used for cervical cancer screening instead of a Pap or cotesting with both an HPV and a Pap test, the researchers say.

In the first paper1, Dr Warner Huh, from the Department of Gynecologic Oncology, University of Alabama, Birmingham, USA, sets out the findings of a panel convened to provide guidance on using HPV as the first-line primary screening test. The panel included representatives from all the major US organizations involved in cervical cancer screening, and addressed questions related to the safety and effectiveness of HPV testing for primary screening and whether it could be considered as an alternative to the screening methods currently in use in the US. The panel was convened because of an application to the Food and Drug Administration (FDA) for an existing HPV test to be used for primary HPV cervical cancer screening. The guidance was based on a literature review and also on review of data from the ATHENA study which was conducted to support the primary screening application to the FDA.

"We found that, in patients aged 25 years and upwards, primary HPV testing performed better than a Pap alone, and we recommend that such tests should be carried out no sooner than every three years. This is an important advance in cervical cancer screening because it offers a better reassurance of low cancer risk compared to Pap screening, which is also carried out at three year intervals," Dr Huh said.

Infection with just two HPV genotypes, 16 and 18, is responsible for about 70% of all invasive cervical cancers worldwide. The panel recommends that patients testing positive for either of these two high risk genotypes should have immediate colposcopy - a procedure using a lighted magnifying device that allows doctors to see abnormal areas in the cervix that would be missed by the naked eye. Women with one of the 12 other HPV genotypes can be followed-up in 12 months with repeat testing with both the HPV test and a Pap.

"We believe that there is still considerable confusion over the three current screening options, and the intervals at which they should be performed. We hope that our deliberations will go some way towards reducing this uncertainty. However, I would still like to see more data from the US, and evidence from other countries using primary HPV screening such as Australia and The Netherlands. But in the absence of data to the contrary, we believe that primary HPV testing has potential to further reduce cervical cancer in the US," Dr Huh said.

The second paper2 reveals end-of-study results of the ATHENA trial which evaluated safety and effectiveness of HPV primary screening as an alternative to Pap in women of 25 years and older. 42,209 women in this age group were enrolled into the trial and had both Pap and HPV testing. Those with abnormal Pap test results and those who were HPV positive were referred for colposcopy.

"We found that HPV primary screening was as effective in women aged 25 years and over when compared to Pap alone for women 25 and 29 and cotesting for those aged 30 and over. However, HPV screening alone requires only one test, and this is important for many women who may not be able to afford the cost of two tests," said Dr Thomas Wright, a Professor Emeritus of Pathology and Cell Biology at Columbia University, New York, USA.

To determine the impact of starting HPV screening at different ages, the researchers compared the prevalence of HPV positivity and Pap abnormalities as well as the three year detection rate of high-grade cervical disease by age group. They found that although HPV positivity was almost twice as high in women aged 25-29 as it was in women aged 30-39, HPV testing identified about twice as many high-grade cervical disease cases in women aged 25-29 than did the Pap.

"When Pap screening is used in this age group, the women with missed high-grade cervical disease are told to return in three years for repeat screening and some are likely to develop invasive cervical cancer", said Dr Wright.

"Our results, from the first prospective US study to evaluate the performance of HPV primary screening, have shown clearly that this new screening approach should be considered as an option for women 25 years and older", Dr Wright said. However, he added that the recent FDA approval for HPV primary screening is limited to a single commercially available HPV test and to only one of the two widely utilised liquid-based Pap tests. "In order to facilitate the widespread adoption of this safe and effective method of screening, it would be advantageous to have additional HPV tests and the other liquid-based Pap tests approved. We hope that our research will help reduce morbidity and mortality from cervical cancer worldwide," he said.

Source: https://medicalxpress.com/news/2015-01-screening-hpv-infection-accurate-pap.html

Chlamydia Infection May Pave Way For Cancer via DNA Damage

The bacterium Chlamydia trachomatis is a leading cause of sexually transmitted disease that infects over 90 million people worldwide every year. Chlamydia infection often goes unnoticed, can persist for years with little or no symptoms, and can damage women's reproductive organs.

As well as this, the bacterium is proving increasingly stubborn to shift: antibacterial drugs are often no longer strong enough to eradicate it completely, so it goes into persistent mode, leading to chronic infection with no symptoms.

Chlamydia Uses Various Tactics to Ensure Survival

Chlamydia uses "Trojan horse" tactics to enter host cells unnoticed. A protein called Pgp3 enhances Chlamydia's ability to enter host cells unnoticed and then evade host defences.

To ensure survival, Chlamydia needs to make the most of the resources inside the host cell, which is where the bacterium spends most of its life. Once inside the host cell, the pathogen goes about changing the cell to make itself at home. It re-arranges host cell processes to favour its own growth and proliferation. But it's not clear how this affects the cell's normal functions and whether it leads to disease.

However, there is evidence that it might: there is a growing mountain of epidemiological data linking Chlamydia infections to the development of cervical and ovarian cancer development. But exactly how this might come about has been somewhat of a mystery - until now.

Chlamydia Causes Lasting Genetic Damage to Host Cells

In this new study, the researchers show that Chlamydia makes a long-lasting impression on the genome and epi-genome of host cells. Such changes are increasingly implicated in the development of a range of cancers.

They found host cells acutely and persistently infected with Chlamydia had increased levels of different kinds of DNA breaks.

In normal cells, when these types of breaks occur, they either go into cell suicide mode (apoptosis, where the cell is removed, broken down and its material parts recycled) or DNA repair mode.

In DNA repair mode, special proteins trigger a process called DNA Damage Response which attempts to reseal the broken strands of DNA to make sure the correct sequence of genetic code is restored (so when the cell replicates it produces healthy daughter cells).

But not only did the researchers find that Chlamydia-infected cells had altered DNA, but also that their DNA Damage Response didn't work properly: so the broken DNA didn't get repaired in those cells that didn't go down the cell suicide route.

Chlamydia disrupted the host cell DNA Damage Response by stopping key proteins from reaching the sites of DNA damage.

Chlamydia Damage to Cells Is Similar to that Which Leads to Cancer

Thus Chlamydia-infected, damaged cells that did not go down the cell suicide route continued to proliferate, passing on the DNA damage, and also spurred by some extra pro-survival signals activated in the host cell by the pathogen.

The result is an increasing population of rogue host cells that have escaped the normal mechanisms that ensure faulty DNA is not replicated: a hallmark of cancer.

The discovery is important because if it is established that an infection leads to cancer, then vaccination to prevent the infection, or antibiotics to eliminate it, may also prevent the cancer.

Such preventive methods are already working with other cancer-causing agents such as Human Papilloma Virus (HPV) and Helicobacter pylori, which can cause cervical and gastric cancer, respectively.

However, the path from infection to cancer needs to be firmly established before such a strategy can be considered in the case of Chlamydia.

Source: https://www.medicalnewstoday.com/articles/262350.php

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