HPV

2022 - 5 - 31

Post cover — Image courtesy of "The Conversation AU"

What are HeLa cells? A cancer biologist explains (The Conversation AU)

The immortal cancer cells of Henrietta Lacks revolutionized the fields of science, medicine and bioethics. And they still survive today, more than 70 years ...

After Lacks was infected with HPV 18, the second-most-common high-risk type of the virus, her cervical cells lost the ability to produce these sentinels. Lacks didn’t know that cells in her cervix were infected with a virus that causes one of the most common sexually transmitted diseases: human papillomavirus, or HPV. There are more than 150 different types of HPVs, but only a small group are known to cause cervical cancer. When Lacks’ cervical cancer cells were successfully grown in a petri dish in 1951, scientists now had a source of cost-effective and easy-to-use cells that expanded their ability to conduct research. From polio and COVID-19 vaccines to cancer research and sequencing the human genome, HeLa cells have played an enormous role in many scientific discoveries and advancements. Henrietta Lacks’ story is also an ongoing bioethics case, because these cells were taken from her during a routine cervical cancer biopsy that was then given to researchers without her consent, as was common practice at the time. As a cancer researcher who uses HeLa cells in my everyday work, even I sometimes find it hard to believe.

HPV screening for cervical cancer is reaching maturity (The BMJ)

In the English Cervical Screening Programme, screening intervals are age dependent, with routine invitations sent at three years for women aged 25-49 years and ...

The authors declare the following other interests: KC and MSa are co-principal investigators of a major screening trial in Australia (Compass), which is coordinated at the Australian Centre for the Prevention of Cervical Cancer (ACPCC), a government funded not-for-profit health promotion charity. HPV screening coupled with appropriate treatment for high grade precancerous cells is a critical pillar in the WHO strategy for global elimination of cervical cancer. In the context of HPV vaccination, which protects against infection with (at least) HPV types 16 or 18, direct referral of women with these infections in the first HPV screening round of the Australian National Cervical Screening Program did not greatly increase referrals. For women older than 50 years, for example, screening intervals longer than five years could be considered (as has already been done in the Netherlands) and discharging of women in this age group altogether after two or more rounds of consistently negative screening results might be possible. However, self-collection of samples for HPV testing is an increasingly important tool for improving the equity and coverage of cervical screening programmes, 14 15 and some loss of sensitivity is reported in this context for mRNA, but not DNA, tests. Alternatives to the English pilot’s approach (cytology) include direct referral for women with some of the highest risk HPV types (HPV 16 and 18), and selective use of cytology to inform the referral decision only for women with other oncogenic HPV types , and use of emerging technologies such as dual stained cytology or methylation markers. Ultimately, this lower rate of detected disease is expected to influence the balance of benefits and harms of screening: changes to the interval, triage approach, or threshold for colposcopy referral might be required in the future. This strategy resulted in immediate detection of a large proportion (>80%) of the invasive cervical cancers seen in that screening round; of these, 20% showed negative cytology and these women would not have been referred with cytology only triage. Women who were HPV positive and had no cytological abnormalities and then at early recall were HPV negative had an increased rate of CIN3+ at the second round of screening. The authors found that women younger than 50 years with a negative first round HPV test result were at much lower risk of cervical intraepithelial neoplasia grade 3 or worse (CIN3+) in the second round (adjusted odds ratio 0.26, 95% confidence interval 0.23 to 0.30) or interval cancers (adjusted hazard ratio 0.44, 95% confidence interval 0.23 to 0.84) than women testing negative on the basis of cytology. Safely increasing the screening interval is an important contributor to the cost effectiveness of HPV screening. Risk of second round CIN3+ for women who were HPV negative in the first round were even lower in individuals older than 50 years (adjusted odds ratio 0.46, 0.27 to 0.79). These findings provide important data on the effectiveness of HPV screening in relation to incident CIN3+.

Cervical cancer screening: Why reducing how often women have ... (iNews)

A study of 1.3 million women in England has provided evidence that shows a longer gap prevents as many cancers as screening at three-year intervals, ...

Researchers found that people eligible for screening under 50 who had a negative HPV screen in the first round had a lower risk of detection of abnormal changes of the cells that line the cervix, otherwise known as CIN3+, in the second round compared to cytology. “The NHS cervical screening programme remains an important way of protecting people – including those who have not been vaccinated – from developing cervical cancer. Samantha Dixon, chief executive of Jo’s Cervical Cancer Trust, said: “Around 80 per cent of us will have HPV in our lives, in the majority cases the body will clear the infection but in some cases it can cause cells to change. So giving time for HPV infections to clear, cells to return to normal, is important. So, if you notice any unusual changes for you, do not wait for a screening invitation – speak to your doctor.” The BMJ study shows that the HPV test is more accurate than a cytology test. Awareness campaigns are also important so we can remind people why the test exists and not to ignore their invite.” “I’m not a scientist but I think it’s important that all the evidence for decisions around screening is really clearly communicated as big changes can sound quite scary. If you live in Scotland or Wales, you will be invited for cervical screening every five years, whatever your age, if you test negative for HPV on your previous test. Ms Flaherty, now 35, said: “In most cases screening picks up any changes before they can develop into cancer so it can prevent you from ever getting it. HPV also increases the risk of some types of mouth and throat cancers. Laura Flaherty was 31 years old when her cervical cancer was detected as a result of a smear test.

Cervical screening every five years just as good as very three (Metro)

The KCL team said that because an HPV infection comes before abnormal cells develop, HPV testing detects more people at risk of cervical cancer. File photo ...

‘It’s important to remember, screening is for people without symptoms. The study found that 1.21 in 1,000 people had a detection of CIN3+ after a negative HPV screen compared to 4.52 in 1,000 people after a negative cytology. They found that people under 50 eligible for screening who had a negative HPV screen in the first round had a lower risk of detection of CIN3+ in the second round compared to cytology tests. Invitations for cervical screenings in England are currently sent out to women and people with a cervix aged 25 to 49 every three years and every five years to those aged 50 to 64. It found that those aged 24 to 49, were less likely to develop cervical lesions, abnormal changes in the cells that line the cervix known as CIN3+ and cervical cancer three years after a negative HPV screen compared to a negative smear test. Researchers at King’s College London (KCL) have said screening women and people with a cervix aged 24 to 49 who test negative for human papillomavirus (HPV) at five-year intervals is just as effective as screening every three years.

New study supports extending cervical screening intervals for ... (Cancer Research UK)

As having an HPV infection comes before abnormal cells developing, HPV primary testing detects people at risk of developing cervical cancer at an earlier stage.

“This builds on findings from years of research showing HPV testing is more accurate at predicting who is at risk of developing cervical cancer compared to the previous way of testing. Extending the interval with HPV primary testing helps to maximise the balance of potential benefits and risks. “It’s important to remember, screening is for people without symptoms. In the pilot, several sites across England partially converted their cervical screening offering from cytology testing to HPV primary testing. Whichever test was used, people aged 24-49 were invited for a second screening test in 3 years if they had a negative result. If abnormal cells were found, people were referred for further testing. People aged 50-64 were invited back in 5 years if they had a negative result. However, for people aged 50-59, this difference wasn’t observed. If no abnormal cells were detected, people were asked to return in 12 months for another test. But the changes were based on years of research into making cervical screening more effective. The process is for women, trans men and some non-binary people and involves a health professional, usually a practice nurse, taking a sample from the cervix that’s then sent off to the lab. But some types, or strains, of HPV are linked to cancer.

Screening for cervical cancer every five years 'could be as safe' as ... (ITV News)

Researchers collected data from 1.3 million women and found introducing HPV testing at longer intervals 'is at least as safe' as more regular testing.

"It's important to remember, screening is for people without symptoms. The study found that 1.21 in 1,000 people had a detection of CIN3+ after a negative HPV screen compared to 4.52 in 1,000 people after a negative cytology. They found that people under 50 eligible for screening who had a negative HPV screen in the first round had a lower risk of detection of CIN3+ in the second round compared to cytology tests. Dr Rebolj said: "They build on previous research that shows that following the introduction of HPV testing for cervical screening, a five-year interval is at least as safe as the previous three-year interval. Currently women in England aged 25 to 49 are invited for cervical screening every three years, while those aged 50 to 64 are invited every five years. Screening for cervical cancer every five years 'could be as safe' as every three

Cervical screening every five years 'prevents as many cancers as ... (The Independent)

Researchers at King's College London said that screening women aged 24 to 49 who test negative for human papillomavirus (HPV) at five-year intervals prevented ...

“It’s important to remember, screening is for people without symptoms. Start your Independent Premium subscription today. By clicking ‘Register’ you confirm that your data has been entered correctly and you have read and agree to our Terms of use, Cookie policy and Privacy notice. The study found that 1.21 in 1,000 people had a detection of CIN3+ after a negative HPV screen compared to 4.52 in 1,000 people after a negative cytology. They found that people under 50 eligible for screening who had a negative HPV screen in the first round had a lower risk of detection of CIN3+ in the second round compared to cytology tests. The study of 1.3 million women in England, published in the British Medical Journal on Tuesday, found that women in this age group were less likely to develop clinically relevant cervical lesions, abnormal changes of the cells that line the cervix known as CIN3+, and cervical cancer three years after a negative HPV screen compared to a negative smear test.

Increasing Cervical Screening Interval to Five Years Is Safe With ... (Technology Networks)

A study of 1.3 million women in England has provided evidence to support the extension of cervical cancer screening intervals from three years to five years ...

Currently in the UK, where the HPV screen is negative, the NHS Cervical Screening Programme in England invites women and people with a cervix aged 25-49 years to test every three years and people aged 50-64 years to test every five years or three years if they test positive. As with any change to a screening programme, this will be monitored to ensure that cervical screening is as effective as possible for all who take part. Researchers found that people eligible for screening under fifty who had a negative HPV screen in the first round had a lower risk of detection of CIN3+ in the second round compared to cytology. This builds on findings from years of research showing HPV testing is more accurate at predicting who is at risk of developing cervical cancer compared to the previous way of testing. The study shows that the HPV test is more accurate than a cytology test. As having HPV infection comes before having abnormal cells, HPV testing detects more women at risk of cervical cancer.

Single LR-HPV infection exists in minority HSIL patients. | IDR (Dove Medical Press)

The status of human papillomavirus infections in women in Yunnan in the south of China and their correlation with grade of cervical intraepithelial ...

Single subtype infection and multiple subtype infection have different impacts on CIN. Kim et al 20 compared the HPV genotypes of 236 patients with a multiple subtype infection and 180 patients with a single subtype infection, and they found that the correlation between multiple subtype infections and HSIL was closer than that between a single subtype infection and HSIL. The infections were also seen to last longer in patients with multiple subtype infections than in patients with a single subtype infection. The three subtypes of HR-HPV with the highest infection rate were HPV16, HPV52 and HPV58. HPV43 is the main subtype of LR-HPV. There was no correlation between ethnicity and single or multiple infections in different CIN groups. The main HR-HPV subtypes were 52 (25.3%), 58 (16.1%) and 16 (16.1%) in the LSIL group, and 16 (37.8%), 58 (15.4%), and 52 (11.2%) in the HSIL group. In the LSIL group, there were 39 cases of single infection and 15 cases of multiple infection in han nationality, 19 cases of single infection and 6 cases of multiple infection in minority nationality, χ2= 0.0063, P > 0.05, the difference was not statistically significant. The main LR-HPV subtypes were 43 (23.8%), 42 (19.0%), and 40 (4.8%) in the LSIL group, and 43 (29.4%), 81 (29.4%), and 11 (17.6%) in the HSIL group. This is related to the different susceptibility and clearance rates of different types of HPV in different regions, different nationalities and different physical hosts. Single and multiple infection rates of different ages in LSIL group showed no significant difference (X2 = 2.797, P = 0.258). There was also no significant difference in single and multiple infection rates of different ages in HSIL group (X2 = 5.037, P = 0.081) ( Table 2). In the LSIL group, there were 27 patients (34%) with a single subtype infection in the age range from 30 to 45 years, which was the age group with the highest proportion of single-type infections, and in the HSIL group, there were 83 patients (41%) with a single subtype infection in the age range from 30 to 45 years old, which was also the main single subtype infection age group. In HISL group, there were 131 cases of single infection and 41 cases of multiple infection in han nationality, 22 cases of single infection and 8 cases of multiple infection in minority nationality (χ2=0.0105, P>0.05). It showed that there was no significant difference between ethnic group and single or multiple infection in different CIN groups ( Table 4). However, it should be noted that two ethnic HSIL patients had a single LR-HPV infection. Twelve percent of HSIL patients were <30 years old, and there were 60 patients aged 30–45 years in the HSIL group, accounting for 58% of the group, and this was the age group with a high incidence. Immunohistochemical P16 expression was block-positive reactivity in HSIL patients ( Figure 2), Ki67 index >30% ( Figure 3). Morphological LSIL patients showed negative or mottled expression of P16 and Ki67 index <30%. 2, 3 Human papillomavirus (HPV) infections are known to be closely related to cervical precancerous lesions and cervical cancer, and the main cause of cervical cancer is a persistent infection of high-risk HPV (HR-HPV). 4, 5 Cervical intraepithelial neoplasia (CIN) is a precancerous disease.

Extension of cervical screening intervals with primary human ... (The BMJ)

Women screened with HPV testing who were positive were referred at baseline if their cytology triage test showed at least borderline abnormalities or after a ...

In the three to five years after a negative HPV test (depending on the woman’s age), neither the detection of CIN3+ at the second round nor the frequency of interval cancer incidence showed that the risk of a clinically relevant lesion was increased for APTIMA compared with the DNA tests. The risk was in fact similar to that among 260 266 women younger than 50 years who had negative cytology and were screened again after a three year routine recall (4.5 with CIN3+ per 1000 screened in the second round, table 2). Hence, a routine recall interval not longer than three years would be appropriate for women in the English programme who are HPV negative after early recall. These updated data 5 for women younger than 50 years with almost three million woman years of observation confirmed that the incidence of CIN3+ three years after a negative HPV test is about 74% lower than after negative cytology (adjusted odds ratio 0.26). 1 5 19 20 21 22 They support the English Cervical Screening Programme’s planned extension of the screening interval from three to five years for HPV negative women younger than 50 years and align with practice in other countries. 23 In the pilot study, almost 25 000 women aged 50-59 years who were negative for HPV attended the second round in five years, and their CIN3+ detection was similar to that in the ARTISTIC trial (0.6/1000 screened). This detection is about half of that observed in younger women and is consistent with the findings of a US study that included women who had been through one or more rounds of screening with HPV testing. However, the currently available data and other studies such as the ARTISTIC trial 12 point to the need for programmes such as the English Cervical Screening Programme, to extend the screening interval for HPV negative women older than age 50 years to longer than the current five years. With HPV testing in the first round, the detection of both CIN3+ (adjusted odds ratio 0.16, 95% confidence interval 0.14 to 0.18) and cervical cancer (0.46, 0.32 to 0.67; based on the data reporting the detection of lesions in table 2) was significantly lower at age 50-59 years than at age 24-49 years. Of 1570 women who were HPV positive at screening but HPV negative at early recall, 98 had had a second round screen by the end of 2019, with no reported CIN3+ cases (not tabulated). For both cytology and HPV testing, we determined the detection of (squamous or glandular) CIN3+ and cervical cancer after a positive screening test in each round (first v second). Second rounds were included for all women with negative screening tests in the first round. The safety and acceptability of the screening and early recall protocols had been shown in the ARTISTIC trial, 12 whereas the aim of the pilot study was to demonstrate the feasibility of HPV based screening in a real life setting and on a large scale. Woman years were counted from the date of the negative screening test until the date of cancer diagnosis, date of a screening test in the second round for ages 24-59 years, date of colposcopy for ages 60-64 years (if any at all), or 31 December 2018 (that is, end of the English National Cancer Registration and Analysis Service data), whichever came first. We also assumed that women who have negative HPV test results but have similar risks as women with negative cytology of CIN3+ or cervical cancer, or both, should be rescreened with the same routine recall intervals, whereas for women with lower observed risks, extension of the routine recall intervals is possible. Supplementary figure S1 shows the completeness of data for early recall in the first round and for primary screening and early recall in the second round by age group.

It's time to get comfortable discussing HPV (RDH)

I said, “I would love to share! Thank you for asking. What we now know is that the human papillomavirus (HPV) is the main cause of oropharyngeal cancer. It's ...

The public and some medical and dental professionals are misinformed about HPV. It is still the common belief that HPV is most associated with causing cervical cancer and the purpose of the HPV vaccine is to help prevent cervical cancers in females. Her job was to be a patient advocate and educate the community.” I’m encouraging you to be like Irene Newman: be an advocate and educate the community, share the tremendous amount of knowledge, expertise, and lifesaving information you possess about “our cancer,” not only with patients, but the general public as well. I was very uncomfortable with this conversation at first; however, I knew it was vital information to my patients’ oral and systemic health and it needed to be shared. The physician mentioned HPV and its association with cervical cancer and mentioned the HPV vaccine. It’s okay, even essential, to talk about the transmission of HPV via oral sex, its association with head and neck cancers, and the availability of the HPV vaccine that can aid in reducing persistent HPV infections associated not only with oropharyngeal and cervical cancer but also anal, penile, vaginal, and vulvar cancers. When I first started sharing information about HPV with my patients 12 years ago, I would bring it up when I was palpating the occipital nodes behind them so I wouldn’t have to look at them. The public wants to know how to help prevent cancers and recognize the signs and symptoms for the earliest detection. The messaging for cancers such as breast cancer, colon cancer, and cervical cancer is intentional in the media and respective medical offices, but not so much for oral cancer. They said they had heard about HPV and cervical cancer but not about it causing cancer in the mouth. He stated he was aware of HPV causing cervical cancer, but not cancer in the mouth. We also discussed the HPV vaccine, which they had both had; however, they didn’t know much about it and didn’t know it could aid in protecting them from persistent HPV infections, which could possibly result in cancer. In the last 12 years of being immersed in raising awareness about HPV and oral and oropharyngeal cancer, I wish I’d kept track of the number of conversations like this that have occurred, inside and outside of the operatory.

HPV

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