Author: Mohsen Shahmanesh

Current vaccines cover only a minority of human papillomavirus (HPV) subtypes associated with cancer and genital warts

Effective vaccination exists for two sexually transmittable viruses, human papilloma virus (HPV) and hepatitis B virus (HBV). Other viruses have proved more problematic. A recent study in the New England Journal of Medicine showed, yet again, that a vaccine for herpes virus remains elusive. The same is true for hepatitis C and even more for HIV.

Thus identifying at risk groups for HPV and HBV is essential for targeting vaccination strategies. Particularly as persistent infection with high-risk sexually transmitted HPVs (HR-HPV) can lead to development of cervical and other cancers, while low-risk types (low-risk HPV) may cause genital warts. In a recent publication by Ann Johnson and colleagues at University College London they explored the epidemiology of different HPV types in men and women in the UK and their association with demographic and behavioural variables.

Data collected for the British National Survey of Sexual Attitudes and Lifestyles, a cross-sectional survey undertaken in 1999–2001 were analysed. Half of all sexually experienced male and female respondents aged 18–44 years were invited to provide a urine sample. They tested 3123 stored urine samples for HPV DNA.

HPV infection, was prevalent in this population, detected in 29% of samples from women and 17% from men. Significantly 13 high risk HPV subtypes were detected in 16% of women and 10% of men. HPV subtypes, HPV types 16/18, which for part of the two available vaccines in the market, were found in only 5% of women and 3% of men. Types 6/11 which are responsible for most cases of genital warts were isolated in in 5% of women and 2%  of men. In multivariate analysis, HR-HPV was associated with new partner numbers, in women with younger age, single status and partner concurrency, and in men with number of partners without using condom(s) and age at first intercourse.

They concluded that HPV DNA was detectable in urine of a high proportion of the sexually active British population. In both genders, HR-HPV was strongly associated with risky sexual behaviour. The minority of HPV infections were of vaccine types that are currently used in the two available vaccines. These cover HPV 16/18 and 6/11 only.

The authors pointed out t is important to monitor HPV prevalence and type distribution following the introduction of vaccination as vaccination itself may alter the prvalence of the difefrent sun

NHS Bill: the case against

As the NHS Bill plods its slow passage into law it has become increasingly clear that a majority of health care workers, both doctors and nurses, do not agree with it in its current form. However most people who oppose the bill are not fully familiar with its details. Dr Clive Peedell, Consultant Clinical Oncologist and member of the NHS Consultant Association has dissected the case against the Bill and presented it in a powerpoint presentation that will be very useful in familiarising opponents of the bill with its details and for arguing the case against it.

Click on Case against NHS Bill to download the powerpoint.

Sexual behaviour as well as HPV types 6 and 11 are associated with genital warts

A recent study by GM Anic et al from  the H. Lee Moffitt Cancer Center and Research Institute in Tampa, Fla., have found that human papillomavirus types 6 and 11, as well as recent sexual behavior, are strongly associated with the incidence of genital condyloma (wart) infection.

The strongest associations were found for infections with HPV types 6 and 11. The risk for condyloma also increased with an increasing number of female sexual partners but decreased with age. Sexual behaviors in the previous 3 months were also associated with a high risk for condyloma: a high number of male anal sex partners, more frequent vaginal intercourse and infrequent condom use. Also influencing the incidence of condyloma was ever having a sexually transmitted infection and ever having a partner with condyloma.

Since subclinical infection with HPV is more common than condylomas, this latter finding suggests that patients with visible genital warts are more likely to transmit condylomata to their sexual partner. This finding confirms an old study by the veteran British venerologist JD Oriel in 1971.

Factors strongly associated with condyloma were incident infection with human papillomavirus (HPV) types 6 and 11 (hazard ratio [HR], 12.42 [95% confidence interval {CI}, 3.78–40.77]), age (HR, 0.43 [95% CI, .26–.77]; 45–70 vs 18–30 years), high lifetime number of female partners (HR, 5.69 [95% CI, 1.80–17.97]; ≥21 vs 0 partners), and number of male partners (HR, 4.53 [95% CI, 1.68–12.20]; ≥3 vs 0 partners). The results suggest that HPV types 6 and 11 and recent sexual behavior are strongly associated with incident condyloma.

“The strong association between recent sexual history and incident condyloma after accounting for HPV infection suggests that prevention efforts targeting behavioral modification may be effective at reducing condyloma incidence among men who have not received the HPV vaccine,” the researchers wrote.

Central obesity is a risk for HIV-associated cognitive impairment

Because effective antiviral therapy can suppress HIV replication and prolong the life of HIV-infected patients to that approaching non-infected individuals long term complications of antiviral therapy acquire particular importance. Among these are neuro-cognitive disorders.

Neurocognitive impairment, ranging from mild deficits to severe dementia, occurs in about half of HIV-infected individuals. A recent study by McCutchan et al has suggested that increased waist circumference was associated with increased prevalence of neuroognitive impairment in a subgroup of HIV-infected patients followed up in the CNS HIV AntiRetroviral Therapy Effects Research (CHARTER) study. They found that central obesity, but not more generalized increases in body mass (BMI), was associated with a higher prevalence of neurocognitive impairment (NCI) in HIV+ persons. Diabetes appeared to be associated with NCI only in older patients.

These findings are similar to those reported in the non-infected populations with central obesity – known as metabolic syndrome. the mechanisms for these findings are unclear. However as central obesity and metabolic syndrome appear to be common in HIV-infected patients receiving antiviral therapy these findings may have important implication for patients.The authors concluded that avoidance of antiretroviral drugs that induce central obesity might protect from or help to reverse neurocognitive impairment in HIV-infected persons.

Research on the long term metabolic effects of anti-retroviral treatment, which has focused on the mechanisms for increased incidence of cardiovascular disease seen in patients on treatment should be widened to include neurocognitive impairment and its relations to central fat accumulation.

New ways of getting treatment to sexual partners of patients infected with chamydia or gonorrhoea

Treating a sexually transmitted infection in a person is incomplete without treating te sexual partner and thus closing the loop. Current forms of partner notification (PN) are not particularly successful with less than one half of sexual partners attending sexual health (genitourinary medicine) clinics.

A recent study by Claudia Escourt and her colleagues has looked at the feasibility of two different approaches to PN. One was to set up a hotine for the partner to phone a health care worker in the sexual health clinic and after appropriate consultation to collect their treatments either at the sexual health clinic and the secone was for the partner go to a a designated pharmacy and obtain treatment from a trained pharmacist. The partners were also asked to provide urine for chlamydia testing and to attend the sexual health clinic at a time of their own convenience for syphilis and HIV testing.

The preliminary results were encouraging and showed that both systems were acceptable to clients and increased uptake of treatment from 36% to 59% in the case of the clinic hotline and 66% in case of pharmacy.

The only drawback of either strategy was that almost none of the partners accessed HIV or syphilis testing at a later date.

Oral human papillomavirus infection more common in US males

Almost 7 percent of American men and women are infected orally with the human papillomavirus (HPV), new research reveals, with men showing significantly higher infection rates than women. Indeed among those between the ages of 14 and 69, men seem to face a nearly threefold greater risk than women for oral HPV infection.

The study was part of the ongoing National Health and Nutrition Examination Survey (NHANES). To better understand that connection, Gillison’s team sifted through data on nearly 5,600 men and women collected between 2009 and 2011 NHANES. All NHANES participants had been examined in person, during which all were tested for HPV.

In a study published in the Journal of the American Medical Association (JAMA) on Janury 26, 2012 Dr. Maura Gillison, chair of cancer research in the department of viral oncology at Ohio State University’s Comprehensive Cancer Center in Columbus reported  an overall oral HPV infection rate of 6.9 percent, with HPV-16 being the most common type.

Oral HPV incidence varied with age, however, with peak rates occurring among those between the ages of 30 and 34 (at 7.3 percent) as well as among men and women between 60 and 64 (11.4 percent). Overall, oral HPV infection hit the 10 percent mark among men. Among women it was just shy of 4 percent.

While those with a history of smoking, heavy drinking, and/or marijuana use appeared to face a higher risk for infection, sexual behavior also plays a key role in upping a person’s risk. For example, while those who had never had sex faced less than a 1 percent risk for oral HPV infection, prevalence hit 7.5 percent among those who were sexually active. And the greater the number of sexual partners, the higher the risk.

Calls to immunise teenage boys after huge rise in throat cancer

Cases of oropharyngeal cancer have more than doubled to over 1,000 annually since the mid-1990s after remaining stable for many years, Professor Hisham Mehanna, director of the Institute of Head and Neck Studies in Coventry reports.

The Department of Health requested the latest figures from Professor Hisham Mehanna, who has surveyed the incidence of HPV-related oropharyngeal cancer in the UK and other countries. “We are experiencing a very significant rise in oropharyngeal cancer. It used to be rare in our practice – now [head and neck cancer] is the most common cancer we see. All the studies show there is a strong association with oral sex.” It is also occurring in younger patients.

More than 70 per cent of cases are caused by human papilloma virus (HPV), compared with less than a third a decade ago. HPV is transmitted during sex, including oral sex and also possibly spread by open-mouth kissing. HPV is the main cause of cervical cancer in women, affecting almost 3,000 women a year in the UK.

Currently women are offered HPV vaccine to prevent cervical cancer. The quadrivalent vaccine also protests against genital warts in both women and also their male partners and is now being advocated by the Department of Health.

The US is considering offering HPV vaccine to men.

HIV highly homogeneous in early infection

Current findings suggest that the mucosal barrier is the major site of viral selection in sexual transmission of human immunodeficiency virus type 1 (HIV-1), transforming the complex inoculum to a small, homogeneous founder virus population. In a recent study from Zurich the authors analyzed HIV-1 viral seqiuences in the C2-V3-C3 region in 145 patients with characteristics  primary HIV-1 infection. They found that  the meedian viral diversity within env was 0.39% (range 0.04%–3.23%). Viral diversity did not correlate with viral load, but it was slightly correlated with the duration of infection.

They also found that  neither transmission mode, gender, nor STI predicted transmission of more heterogeneous founder virus populations. Only 2 patients (1.4%) were infected with CXCR4-tropic HIV-1 with a duakl-tropic R5/X4-tropic–mixed population. The other patients were infecetd by the CCR5-trophic virus which targets the macrophage series.

The authors concluded that transmission of multiple HIV-1 variants might be a complex process that is not dependent on mucosal factors alone. CXCR4-tropic viruses can be sexually transmitted in rare instances, but their clinical relevance remains to be determined. These results have imprtant implications for vaccine development.

An alternative explanation for these results, not discussed by the authors, is that the individuals were infected by a small number or even a single CCR5-trophic virus which subseqeuntly mutates to the complex virus soup that is seen in long-term infected subjects.

Measuring Quality in Sexual health Services

There are a number of reasons why providers of sexual health services might wish to measure quality. Advances in technology, economic uncertainty and increased media coverage of medical errors have created a focus on improving quality in healthcare by those commissioning services, and central guidance in many healthcare systems encourages providers to make services more patient centred. The need to improve quality is also driven by funding mechanisms which often reflect the number of patients attracted to a service and increasingly include a penalty for failing to meet minimum quality standards.

Quality encompasses patient safety, patient experience and the effectiveness of care.  It is multidimensional and its interpretation may vary between commissioners, providers and patients.  Despite this apparent heterogeneity, four key components of quality can be defined: accessibility, acceptability, effectiveness and efficiency.

Accessibility defines how easy it is for patients to get to, and be seen at, a sexual health service. The majority of sexual health patients self-refer, and therefore ease of access is an essential factor when choosing whether to attend a clinic or making a choice between different clinics. Measuring the accessibility of a service can be achieved by formally reviewing clinic location, transport links and parking facilities, although these may not be easily amenable to change. Physical factors, including disabled access, should be easier to change, with the aim of complying with local legislation. Providers have the potentially greatest influence over organisational issues, for example, the percentage of patients seen outside working hours.

Acceptability relates to whether the services provided are perceived to be satisfactory by the patient. Acceptability is also an outcome or consequence of care that may influence subsequent consulting behaviour and health-related decision making.  In either case, evaluation of the opinions of both users and providers is needed.

Effectiveness is whether a service delivers care correctly when assessing the patient’s problem, undertaking appropriate investigations and giving the correct treatment. This encompasses clinic systems to deliver care, individual patient management, and ensuring patient safety.

The limited availability of healthcare resources (including funding, technology and labour) requires them to be used in the most efficient way to maximise outcome. A number of techniques have been developed to measure efficiency in healthcare, for example, cost-effectiveness analyses (the change in cost against change in outcome for a specific disease) and quality-adjusted life years (used in cost utility analyses to calculate the ratio of cost to number of years of life gained for a particular health intervention).  New technology and changes in working practices offer the greatest opportunities to improve efficiency, but require an assessment of associated costs and benefits, which may be both financial and non-financial, for example, improved patient satisfaction, greater diagnostic sensitivity.

A shift in focus from volume to quality of care is increasingly driving change in sexual health services.  However, if measuring quality is to translate into improvement in patient care, a number of key practical questions still remain to be answered, including:

Which bundle of measurements best discriminates between good and poor quality?

How can quality data be most effectively used to effect change and improve outcomes?

See: How to assess quality in your sexual health services. Emma Hathorn, Lucy Land , and Jonathan Ross.  Sex Transm Infect 2011;87:508-510 doi:10.1136/sextrans-2011-050107

Vitamin D deficiency and cardiovascular disease: more information needed

Vitamin D deficiency is common in the general population. It has been linked with hypertension, myocardial infarction, and stroke, as well as other cardiovascular-related diseases, such as diabetes, congestive heart failure, peripheral vascular disease, atherosclerosis, and endothelial dysfunction.

Yet a recent publication in The Annals of Internal Medicine  has highlighted the conflicting nature of the information available, as it relates to increased cardiovascular disease, and has called for proper prospective randomised studies.

Vitamin D deficiency, along with cardiovascular disease, diabetes and some malignancies are more commonly seen in HIV infected patients compared to age-matched controls. While the mechanism for the vitamin D deficiency in HIV infection is still unclear, this deficiency has been shown to be associated with an increased prevalence of type 2 diabetes mellitus.

In a cross sectional study of their HIV cohort in Pennsylvania, USA, Guaraldi and colleagues showed an almost doubling (OR 1.85 CI 1.03-3.3) of diabetes mellitus in those with vitamin D levels below 20 ng/ml compared to those with normal levels. The authors controlled for vitamin D supplementation, sex, age, body mass index (BMI), and hepatitis C, all of which are known to effect glucose metabolism.

We urgently need prospective studies to confirm these findings and to answer the question if vitamin D supplementation will prevent these putative complications of vitamin D deficiency.