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ID- HPV

Primary Care Corner by Geoffrey Modest MD: pap in women with HPV vaccine jnci2016

19 Oct, 16 | by EBM

By Dr. Geoffrey Modest

Given the recent 2 articles on cervical cancer screening (http://blogs.bmj.com/ebm/2016/10/12/primary-care-corner-with-geoffrey-modest-md-cervical-cancer-screening-less-frequently/ and http://blogs.bmj.com/ebm/2016/10/17/primary-care-corner-with-geoffrey-modest-md-cervical-screening-guidelines-from-asco/), I thought I would add (briefly) a third to the troika (see doi: 10.1093/jnci/djw216). Funded by National Cancer Institute of the NIH and done by Harvard School of Public Health.

Details:

  • This is a mathematical modeling of the cost-effectiveness of different cervical cancer screening approaches in HPV-vaccinated women
  • They looked at different levels of cost-effectiveness thresholds: from $50K to $200K per quality-adjusted life-year (QALY) gained

Results:

  • In women who were fully vaccinated with either the bivalent or quadrivalent HPV vaccine, optimal screening strategies involved either cytology or HPV screening alone every 5 years starting at age 25 or 30 (cost-effectiveness ratios ranging from $34,680 to $138,560 per QALY gained
  • In women vaccinated with the nonavalent vaccine (that being: 9 HPV genotypes), only HPV testing by itself was efficient, with both decreased frequency (every 10 years) and starting later at age 35 ($40,210 per QALY) or age 30 ($127,010 per QALY)
  • If there were in reality decreased nonavalent vaccine efficacy, then the 10-year HPV screening should start at age 25 or 30.

Commentary:

  • This article does highlight the issue mentioned briefly in the prior 2 blogs: HPV vaccination might significantly change the cervical cancer screening algorithm
  • The nonavalent vaccine, the one we use now, covers 90% of the carcinogenic HPV types (including the biggies 16/18), as well as 2 of them (6/11) associated with noncarcinogenic genital warts
  • But, there are certainly concerns about directly applying the above:
    • The US rates of HPV vaccination remain <50%
    • There are very limited real-world data on the effectiveness of the vaccines in reducing HPV infection and, especially, the development of precancerous or cancerous lesions
    • This relies on mathematical modeling, which without any real data, is likely fraught with potential errors in assumptions
    • There is potential collateral benefit from screening less: fewer harms from unnecessary colposcopies (???though are we missing some of the “necessary” ones??)
  • So, this adds some to the argument that we need to screen less. The analysis/conclusions would be different if women did not receive the vaccine before they had sexual relations (though, important to remember that HPV can be transmitted without penetrative sexual relations), or did not receive the full series of shots. And the real issue is waiting for real data about the effects of vaccinations in the real world on the incidence of actual CIN and advanced cervical cancer and morbidity/mortality. I am also a little leery about the effect of doing many fewer pelvic exams: I find now that some newer clinicians are less confident doing them, and sometimes do not do them when there are clear clinical indications. This potential adverse effect should somehow be factored into the risk/benefit analysis…

Primary Care Corner with Geoffrey Modest MD: New STD treatment guidelines

24 Jun, 15 | by EBM

By: Dr. Geoffrey Modest

The CDC just updated their guidelines on the treatment of sexually transmitted diseases (see here).

They offer the usual advice to do detailed risk assessment for STDs and HIV, counseling about prevention, making sure immunizations are up to date (eg HPV, hepatitis A and B — they do limit hepatitis A vaccine to MSM, injection drug users, and those with HIV or chronic liver disease; though those of you privy to my prior blogs know that I strongly favor all getting hepatitis A vaccine, given the occasional outbreaks in the US, the increasing travel to countries where hep A is prevalent, the lack of adverse effects from the vaccine, and the fact that it is now being given to all little kids). They also comment on the use of treating HIV aggressively (treatment as prevention, also see here) and the utility of  pre-exposure prophylaxis (the recent CROI meetings had several important papers on this, including the IPERGAY trial, which showed that 2 tabs of tenofovir/emtracitibine (truvada) 2-24 hours before unprotected sex in serodiscordant couples, then 1 tab in 24 hours, and another in 48 hours was stopped early because of efficacy).

Here are some of the changes over previous guidelines:

–sections on transgender men and women (noting the high prevalence of HIV in transgender women — ie, transgender male to female)

–mycoplasma genitalium, in 15-20% of male urethritis, and 30% of men with recurrent urethritis (ie more common than gonorrhea and chlamydia). Pathogenic role in women less clear, though is found in both asymptomatic and symptomatic women (10-30% of cases of clinical cervicitis and 2-22% of PID cases). Does not respond to beta-lactams such as penicillins/cephalosporins, responds inadequately to a 7-day course of doxycycline  (31% cure rate), but does respond to 1-g single dose of azithromycin (though resistance is emerging). If treatment-resistant, can try moxifloxacin (400mg daily for 7,10, or 14 days). Not tested extensively, but small reports of very high cure rates. Consider 14-d course if treatment-resistant PID. Treat sex-partners.

–patients with HIV should have annual screening for hepatitis C in those at high risk for infection

–urethritis: best test for men is NAAT (nucleic acid amplification test) in urine for GC/chlamydia. Same treatment (azithro 1 gm once or doxycycline 100 bid for 7 days), though M gentalium (the most common cause of persistent or recurrent non-gonococcal urethritis) responds better to azithro (see above). Also consider trichomonas. No NAAT is FDA-approved for men, but can still do a urinary test or just treat empirically (and I have seen several cases of symptomatic presumptive trich urethritis in men, responding to treatment with metronidazole)

–cervicitis: test for cervicitis or PID with NAAT of vaginal, cervical, or urine samples (though you should check with your lab. Ours finds lower sensitivity with urine specimens). First catch urines are more sensitive, esp for chlamydia. Or can do self-collected vaginal swabs. Also evaluate women with cervicitis for BV and trichomonas. Consider treating M genitalium, as above, if persistent cervicitis after using azithro or doxycycline.

–gonorrhea: as in prior guidelines, given emergence of resistance, should be treated with both ceftriaxone 250mg IM, and azithro 1 g (though can use cefixime 400mg if ceftriaxone is not available).

–vaginal discharge: no signif changes that i detect, but they do note that BV can be associated with ureaplasma and mycoplasma, and that all women with BV should be tested for other STDs and HIV. For trich infections: 70-85%  have minimal or no symptoms, 2-3x increased risk for HIV acquisition, and NAAT is the preferred diagnostic method (picking up 3-5x more infections than wet mounts). Candida: nonalbicans candida is pretty common, >50% of women with it are minimally or not symptomatic, and treatment remains unclear (?longer duration of nonfluconazole azoles, using 600mg boric acid).

–PID: now <50% associated with gonorrhea or chlamydia. Lots of “normal” vaginal microorganisms and others (mycoplasma, ureaplasma, CMV, M genitalium) have been implicated. no change in management

–HPV updated section on vaccines and alternative treatments. advised not to use podophyllin (irritation, occ severe systemic toxicity)

–anal cancer screening: data insufficient to recommend routine screening for people with HIV, MSM without HIV, general population

–section on sexual assault and abuse/STDs: pretty complete (to me), includes using NAATs for chlamydia and gonorrhea at sites of penetration, as well as trich. Also check HIV, hep B and syphilis

Overall, this is a very comprehensive, 110-page document (138-page, if include references), with pretty much everything related to STDs including clear and highlighted treatment regimens, and, I think, would be reasonable to download onto your computer desktop if you see patients with sexually transmitted diseases…​

Primary Care Corner with Geoffrey Modest MD: HPV vaccine recommendation update

1 Apr, 15 | by EBM

By: Dr. Geoffrey Modest

The Advisory Committee on Immunization Practices of the CDC  just updated their HPV vaccination recommendations to include a 9-valent vaccine (see here​). There are now 3 approved vaccines: Cervarix, a bivalent one against strains 16,18; Gardisil, a 4-valent one against 6,11,16,18; and now Gardisil-9, against 6,11,16,18,31,33,45,52,58. the 4-valent (4vHPV) and 9-valent (9vHPV) ones are licensed for use in men and women.

Data:

–Background: in the US 64% of invasive HPV-associated cancers are attributable to strains 16 or 18, and 10% are attributable to the new strains covered in 9vHPV.

–Phase III study comparing 9vHPV with 4vHPV​ in 14K females 16-26 yo found 96.7% efficacy to prevent >=CIN2 caused by the covered strains of 31,33,45,52,58 (there were very few caused by 6,11,16,18, but immunogencity against these strains was not inferior to that of 4vHPV)

Untitled

–Seroconversion rates against all nine strains was >99%

–Safety profiles of 9vHPV and 4vHPV​ were similar, most adverse events were injection site-related (pain, swelling, erythema), though these local reactions were more common with 9vHPV (40.3% vs 29.1%). Males have fewer injection-site reactions than females.

–Recommendations: routinely begin at age 11-12, but can start at age 9. Vaccine also recommended for females aged 13-26, males 13-21. Males 22-26 may be vaccinated when MSM or immunocompromised (including HIV).

–Injection intervals: the same for all 3 vaccines: minimal interval of 1-2 months between 1st and 2nd dose, then 3 months minimum between 2nd and 3rd dose but maintain 6 months between 1st and 3rd dose.  No data on the immunogenicity of <3 doses of vaccine (this should be studied, given the cost and adverse reactions to this vaccine. I have seen studies in the past looking at 2 doses of the earlier vaccines showing reasonable immunogenicity)

–Not recommended in pregnancy, but no need to get a pregnancy test to give the vaccine and no intervention needed if given during pregnancy (though the CDC would like to track these patients, and it is reassuring that there were no pregnancy-related issues with the prior 2 vaccines, including 4vHPV​ which is made basically the same way)

So, seems reasonable. Lots of details are remaining, such as what to do if there is a long interval between the vaccines (is there any time delay where one has to restart the process?). Or what to do if the patient has already started one of the previous vaccine regimens, though in any case the CDC recommends completing the series, since all of them get the big villains (strains 16,18). But given the lack of immunogenicity studies with fewer than 3 doses of 9vHPV, it is hard to say that there is any utility of switching midstream to 9vHPV​ — ie, there would only be 1 or 2 doses covering the new strains and is this clinically efficacious? Also, the new vaccine is applicable only to those never vaccinated (ie, don’t give the new vaccine if the patient has had either of the 2 other approved ones).

Primary Care Corner with Geoffrey Modest MD: Primary HPV testing for cervical cancer — interim guidelines

22 Jan, 15 | by EBM

Interim guidelines were just released on primary HPV testing in women for cervical cancer (i.e., without doing a pap smear at the same time), from the Society of Gynecologic Oncology and the American Society for Colposcopy and Cervical Pathology, and including experts from the American Cancer Society and American College of Obstetrics and Gynecology (see doi.org/10.1016/j.ygyno.2014.12.022​). Their conclusions were largely based on a prospective company-sponsored cohort study of 47,208 US women, finding that for primary HPV testing as compared to cytology alone (respectively):

–the sensitivity for >CIN2 was 58.26% vs 42.63%

–the risk of >CIN2 (positive predictive value) was 12.25% vs 6.47%

–the risk of >CIN2 in women who were not referred to colposcopy was 0.42% vs 0.59%

–the false positive rate for >CIN2 was 4.09% vs 6.04%

–the improvement in the sensitivity and negative predictive values of HPV testing diminished with age and was not significant in those 50 yo and older

–further analysis found that just doing primary HPV testing in those 25 yo and older was also superior to the current algorithm with cotesting (cytology on everyone starting at age 21 and adding HPV testing in those >30 yo or with abnormal cytology) for both those women with >CIN1 and those >CIN2 (the differences between primary HPV screening and cotesting were still statistically significant though of lesser magnitude than compared with just doing cytology alone, though this analysis compared primary HPV testing every 3 years with cotesting every 5 years​.)

Here is the link to the FDA documents leading to the approval of primary HPV testing (open theFDA Executive Summary).

Their findings:

 

–a negative hrHPV (high-risk HPV) screen provides greater reassurance than negative cytology of not having a CIN3 or higher risk, confirmed in several trials (including European trials)

–primary hrHPV screening can be considered an alternative to either cytology alone or cotesting (cytology plus hrHPV in those 30 yo and older)

–those positive for HPV 16 and 18 should be referred for colposcopy

–those positive for the other hrHPV genotypes tested should get cytolology, with referral for colposcopy if abnormal (ASC-US or more) or followup in 12 months if normal cytology

–data on the time to rescreen is a bit muddled: should be no sooner than every 3 years. some data suggests that 5 years is okay, but data are insufficient to justify that recommendation at this time

–initiate hrHPV screening at age 25 (or 3 years after last cytology, for the group who already began screening at age 21). There was concern about the higher false positive rate for HPV testing in those 25-30 (cotesting, in the old recommendation, started at age 30 because of the combination of high false positive HPV testing in younger women and the fact that progression to cancer is quite uncommon in those <30 yo)

–although there are 4 FDA-approved HPV tests, only the cobas test by Roche is approved for primary HPV testing.

–their conclusion: “primary hrHPV​ testing can be considered as an alternative to current US cytology-based cervical cancer screening approaches including cytology alone and cotesting”.

 

so, there are definitely issues here, some elucidated in prior blogs on this issue (see below).

–one issue is performing hrHPV testing in those 25-30 yo. Will there be more false positives leading to more colposcopies, and their attendant morbidities and costs? Perhaps we should we continue with cytology til age 30 then switch to primary hrHPV testing?

–if the testing interval is every 3 years, there will be lots more tests done, leading to both more pelvic exams (patient discomfort) and cost. One issue noted above is the improved performance of hrHPV every 3 years over cotesting every 5 years — this raises the question as to whether the older recommendations of cotesting 5 years is adequate  — ie, should cotesting be every 3 years, especially in those at higher risk???

–also, since the utility of HPV testing decreases by age 50, should we revert to cytology alone, which is much cheaper?

Here is blog from April:

 

The FDA approved an HPV DNA test for women >25 yo today (see here). the approved test (cobas test, by Roche) tests for 14 high-risk HPV types, including HPV 16 & 18. the FDA, citing a study by Roche, Notes:

 

–women positive for HPV 16 or 18 should go directly to colposcopy (HPV 16 or 18 are responsible for 70% of cervical cancer)

–women positive for the other 12 types should get a regular Pap test to see if need colposcopy

–although initially approved by the FDA in 2011 as a co-test with Pap, this approval now allows HPV testing to be either part of a co-test with Pap, or a primary screening test.

–the Roche study involved 40K women > 25yo, doing colposcopy/cervical biopsy on those with positive Pap or HPV as well as some women negative for both, with 3 year follow-up, leading to the FDA approval

 

So, raises several questions (i have not seen the Roche study, so cannot comment further on that). Given that 90% of HPV infections are transient and given the high frequency in women <30yo (as well as the increased likelihood that the infection would be transient), the previous guidelines were to avoid HPV testing til age 30. Will lowering it to 25, as per the FDA, lead to more unnecessary invasive procedures in those 25-30 years old? It certainly will help Roche’s bottom line…

 

Here is blog from March: 

 

NY times reports unanimous vote by FDA subcommittee to replace pap smears with HPV testing alone. Prior to this being a new policy, has to be approved by FDA (which almost always happens), though many providers may not use this test alone unless approved by professional societies. the initial test would be done at age 25 (for full article).

 

Of note,

–approx cost (in Houstin, Texas): $50 for pap, $150 for HPV

–only one of the hpv tests, the one by Roche (not the most common one done), is approved

–the current guidelines (pap age 21-30 q3yrs, then combo pap/HPV after age 30 q5yrs), have consciously postponed hpv screening til age 30 because in younger sexually active women, these infections most often regress spontaneously and, if picked up by screening, could lead unnecessarily to more invasive followup procedures (eg colposcopy and maybe more).

 

Prior blog from last year:

 

An article this week in the lancet found at that HPV-based cervical cancer screening was better than cytology-based methods (see doi.org/10.1016/S0140-6736(13)62028-0).  They looked at four randomized trials in Europe, with 176,000 women aged 20-64 assigned to HPV-based screening (in 3 of these studies it was combination cytology plus HPV) versus cytology screening alone.  Women were followed on average of 6.5 years to assess the development of invasive cervical carcinoma, with a screening interval of 3 years for those with a negative result.  107 invasive cervical cancers were found.  Although there was not any difference in the first 2-1/2 years of followup, thereafter it was found that HPV-based screening provided 60-70% greater protection against invasive cervical carcinoma as compared with cytology. Their finding was even more significant in women in the 30-34 age range, an unanticipated result. They felt their data supported HPV screening from age 30 with screening intervals of at least every 5 years.

 

Results from this study reinforce the decision at our Health Center (as per ACOG and USPSTF) to screen every 5 years for women aged 30 or older with HPV-based screening.  However, as recommended, we do the combination of cytology with HPV screening.   The study authors do raise the issue “because cotesting leads to many unnecessary colposcopy procedures, stand-alone HPV testing also seems recommendable”. So, maybe we should be doing only HPV testing in women over the age of 30??

 

This article also raises peripherally the issue of cervical cancer screening in a woman who has never been sexually active, or continued cervical screening on patients who have had negative prior HPV screening and are no longer sexually active (the subtext here is: cervical cancer is basically a sexually transmitted disease caused by certain specific strains of HPV).  I personally do not perform cervical cancer screening in women who have never been sexually active (the issue here, though, is to make sure you feel certain that the woman really has not been sexually active). For women who have had adequate negative screens (eg, normal HPV screens twice in the preceding 10 years), and have not been in a sexual relationship for several years and with a very high probability of not getting into one (as with many of our patients from some different cultural backgrounds), it seems reasonable to me to stop screening. (And, not so surprisingly, when i ask if they would like a vaginal exam, the answer is almost always a resounding “no”). This is not the recommendation of ACOG or USPSTF, but seems to make sense based on the information at hand.

Primary Care Corner with Geoffrey Modest MD: Whither the pelvic, again

29 Oct, 14 | by EBM

BMJ had a recent systemic review and meta-analysis of urinary screening for HPV (DOI: 10.1136/bmj.g5264), including 14 studies with 1443 women, comparing urine HPV DNA screen with cervical DNA screen.

Untitled

Findings:

–Urine detection of HPV had a pooled sensitivity of 87% (CI: 78-92%), and specificity of 94% (CI: 82-98%)

–Urine detection of high risk HPV (15 serotypes assessed) had a pooled sensitivity of 77% (CI: 68-84%), and specificity of 88% (CI: 58-97%)

–Urine detection of HPV 16/18 (the worst of the high-risk) had a pooled sensitivity of 73% (CI: 56-86%), and specificity of 98% (CI: 91-100%)

–Translation of above: the high specificity suggests that positive test results are 15 times more likely to occur in HPV positive women; the less-high sensitivity suggests that a negative test results would happen only 7 times more frequently in non-infected women. For those with HPV​ 16/18, positive test results are 37 times more likely to occur in HPV positive women and negative test results would happen only 4 times more frequently in non-infected women.

–Sensitivity for urinary HPV testing increased with first void urine, on meta-regression analysis

So, we have moved away from annual pelvic exams for pap smears and gc/ct (gonorrhea/chlamydia) screening of yore to much less frequent pap smears (beginning later, at age 21, and with frequency of every 3-5 years depending on age and HPV testing, and with several European countries currently assessing doing only HPV testing without cytology). And now perhaps we are moving to just doing urine testing for HPV in the future, maybe even as a sole initial screen. And we have transitioned from cervical gc/ct screening to urine gc/ct tests. In addition, women with vaginal discharges are often appropriately self-treating (eg for yeast) or getting medications for various infections without pelvic exams (eg, urine testing for trichomonas, or simply empiric therapy for bacterial vaginosis/BV). As a result, as clinicians we certainly are doing many fewer pelvic exams now as compared to a couple of years ago. Though, clearly, pelvic exams are invasive, uncomfortable procedures that many women would love to avoid, I do have one caveat. I have seen several episodes where a woman has potential PID and the clinician is comfortable with just sending a urine for GC/chlamydia. The issue here is that GC and chlamydia are not the only culprits (the data are a bit murky here, since there are so many potentially infectious pathogens in the vagina, but it is likely that PID is caused by mycoplasmas, ureoplasmas, BV, and, very often, mixed organisms – both aerobic and anaerobic). And there can be other causes of acute pelvic pain besides PID (eg, ovarian cysts, appendicitis, endometriosis, assorted GI problems including bowel obstruction and constipation…). Again, I think it is great that we clinicians need to do fewer pelvic exams. My concern is that this mind-set may lead to not doing one when it is clinically indicated.

Geoff

Primary Care Corner with Geoffrey Modest MD: FDA approval of stand-alone HPV testing

3 Jun, 14 | by EBM

The FDA approved an HPV DNA test for women >25 yo  (see here). the approved test (cobas test, by Roche) tests for 14 high-risk HPV types, including HPV 16 & 18. the FDA, citing a study by Roche, notes:

–women positive for HPV 16 or 18 should go directly to culposcopy (HPV 16 or 18 are responsible for 70% of cervical cancer) –women positive for the other 12 types should get a regular Pap test to see if need culposcopy –although initially approved by the FDA in 2011 as a co-test with Pap, this approval now allows HPV testing to be either part of a co-test with Pap, or a primary screening test. –the Roche study involved 40K women > 25yo, doing culposcopy/cervical biopsy on those with positive Pap or HPV as well as some women negative for both, with 3 year follow-up, leading to the FDA approval

so, raises several questions (i have not seen the Roche study, so cannot comment further on that). given that 90% of HPV infections are transient and given the high frequency in women <30yo (as well as the increased likelihood that the infection would be transient), the previous guidelines were to avoid HPV testing til age 30. will lowering it to 25, as per the FDA, lead to more unnecessary invasive procedures in those 25-30 years old? it certainly will help Roche’s bottom line… review the blog from 3/18/14 (see here) of note,

–approx cost (in houstin texas): $50 for pap, $150 for HPV –only one of the hpv tests, the one by roche (not the most common one done), is approved –the current guidelines (pap age 21-30 q3yrs, then combo pap/HPV after age 30 q5yrs), have consciously postponed hpv screening til age 30 because in younger sexually active women, these infections most often regress spontaneously and, if picked up by screening, could lead unnecessarily to more invasive followup procedures (eg culposcopy and maybe more).

this will also append a prior blog from last year (see here geoff

Primary Care Corner with Geoffrey Modest MD: HPV screening alone recommended by FDA subcommittee

18 Mar, 14 | by EBM

NY times reports unanimous vote by FDA subcommittee to replace pap smears with HPV testing alone. prior to this being a new policy, has to be approved by FDA (which almost always happens), though many providers may not use this test alone unless approved by professional societies. the initial test would be done at age 25. for full article, click here

of note,

–approx cost (in houstin texas): $50 for pap, $150 for HPV
–only one of the hpv tests, the one by roche (not the most common one done), is approved
–the current guidelines (pap age 21-30 q3yrs, then combo pap/HPV after age 30 q5yrs), have consciously postponed hpv screening til age 30 because in younger sexually active women, these infections most often regress spontaneously and, if picked up by screening, could lead unnecessarily to more invasive followup procedures (eg culposcopy and maybe more).

see prior blog posted last year here.

geoff

 

Primary Care Corner with Geoffrey Modest MD: HPV vaccine and decrease in cervical abnormalities. Maybe.

11 Mar, 14 | by EBM

article last week in BMJ from Australia finding that HPV vaccination in females led to decrease in high grade cervical abnormalities (see doi: 10.1136/bmj.g1458). not an RCT, but a case-control study “real-world” study to see if effect of prior vaccination on first cervical screen. results:

–females offered free quadrivalent HPV vaccine aged 12-26.
–at time of first pap smear, high grade cases in 1062 women, “other cases” (any other abnormality) in 10,887, and normal cytology (controls) of 96,404
–odds ratio for exposure to 3 doses of HPV vaccine vs no vaccine 0.54 for high grade cases and 0.66 for “other cases”, vs controls (ie vaccine effectiveness of 46% and 34%, with number needed to vaccinate being 125 and 22 respectively)
–if got only 2 of the 3 shots for vaccination, odds ratios of 0.79 for both high grade as well as for “other cases” (ie, vaccine effectiveness of 21% for each)
–on further analysis of their data,

–effectiveness of vaccination was not even close to being significant in the oldest age stratum (age 23-27)
–standard pap smears done at that time (2007-2011) first done between age 18-20 in sexually active women, or 1-2 years after first sexual intercourse, whichever is later
–of the 1062 high grade abnormalities, 7 were invasive squamous cell ca, 944 CIN 3, 84 CIN 2, 1 adenoca microinvasive, and 11 adenoca in situ
–1/3 of paps done age 15-18, 1/3 age 19-22 and 1/3 age 23-27

so, i bring this up mostly because of the strong title of the article and that it seems to be getting some play in the press. not sure how really useful it is, given that most of the patients were under 22 (and we stopped doing pap smears before age 21 given the very high number of HPV-related abnormalities, the vast majority of which spontaneously regress), and perhaps as confirmation of that, there was no difference in effectiveness of vaccine for high grade cases in those 23-27 years old. there are some similar data from the US finding 50% decrease in HPV types 16,18,6,11 in young women aged 14-19 (again, younger than we are testing with paps) and even in young women for oral HPV 16/18 infection. though it is concerning that there were several cancers (but very low %) in this young group…..

geoff

Primary care corner with Dr. Geoffrey Modest: HPV better than cytology based cervical CA screening

25 Nov, 13 | by EBM

An article this week in the lancet found at that HPV-based cervical cancer screening was better than cytology-based methods (see  http://dx.doi.org/10.1016/S0140-6736(13)62028-0).  They looked at four randomized trials in Europe, with 176,000 women aged 20-64 assigned to HPV-based screening (in 3 of these studies it was combination cytology plus HPV) versus cytology screening alone.  Women were followed on average of 6.5 years to assess the development of invasive cervical carcinoma, with a screening interval of 3 years for those with a negative result.  107 invasive cervical cancers were found.  Although there was not any difference in the first 2-1/2 years of followup, thereafter it was found that HPV-based screening provided 60-70% greater protection against invasive cervical carcinoma as compared with cytology. their finding was even more significant in women in the 30-34 age range, an unanticipated result. They felt their data supported HPV screening from age 30 with screening intervals of at least every 5 years.

Results from this study reinforce the decision at our Health Center (as per ACOG and USPSTF) to screen every 5 years for women aged 30 or older with HPV-based screening.  However, as recommended, we do the combination of cytology with HPV screening.  the study authors do raise the issue “because cotesting leads to many unnecessary colposcopy procedures, stand-alone HPV testing also seems recommendable”. so, maybe we should be doing only HPV testing in women over the age of 30??

this article also raises peripherally the issue of cervical cancer screening in a woman who has never been sexually active, or continued cervical screening on patients who have had negative prior HPV screening and are no longer sexually active (the subtext here is: cervical cancer is basically a sexually transmitted disease caused by certain specific strains of HPV).  i personally do not perform cervical cancer screening in women who have never been sexually active (the issue here, though, is to be certain that the woman really has not been sexually active). for women who have had adequate negative screens (eg, normal  HPV screens twice in the preceding 10 years), and have not been in a sexual relationship for several years with and a very high probability of not getting into one (as in many of our patients from some different cultural backgrounds), it may be reasonable to me to stop screening. (and, not so surprisingly, when i ask if they would like a vaginal exam, the answer is almost always a resounding “no”). this is not the recommendation of ACOG or USPSTF, but seems to make sense based on the information at hand.

geoff

Primary Care Corner with Geoff Modest MD: HPV vaccine–time to use it

23 Oct, 13 | by EBM

a couple of articles on HPV and vaccine:

 

1. CDC reports: A new study looking at the prevalence of human papillomavirus (HPV) infections in girls and women before and after the introduction of the HPV vaccine shows a significant reduction in vaccine-type HPV in U.S. teens. The study, published in [the June issue of] The Journal of Infectious Diseases  reveals that since the vaccine was introduced in 2006, vaccine-type HPV prevalence decreased 56 percent among female teenagers 14-19 years of age. this is in spite of the fact that <1/3 of eligible teenage females get the full vaccine series, suggesting perhaps that there is either herd immunity and/or there is functionally effective immunity with fewer than the full series of shots.

 

2. article in the lancet on association of oral HPV with oropharyngeal cancers (see http://dx.doi.org/10.1016/

S0140-6736(13)60809-0). oropharyngeal cancers disproportionately affect men (oral HPV infections 3x more common in men than women) and some are caused by oral HPV infection, esp with HPV 16 (this HPV type is associated with the rapid increase in oropharyngeal infections in some areas of the world, and one the main culprits for cervical ca in women).  the lancet study looked at the incidence and natural history of oral HPV infections in men from Brazil, Mexico and the US. they checked oral samples every 6 months for up to 4 years. findings:

 

–1626 men aged 18-73 followed for median of 1 year.

–4.4% of men acquired an incident oral HPV infection within 1 year, 1.7% with oncogenic strain (13 strains including HPV 16 and 18), 0.6% with HPV16 (which was most common of the oncogenic strains).

–higher incidence in smokers, independent of sexual behaviors (though other studies have found that oral sex is associated with higher oral HPV infections, this study did not find that oral sex in the past 6 months or ever having oral sex was associated), more common in bisexual than heterosexual men.

–median duration of infection 7 months, with 8 of 18 oral HPV16 infections persisting for 2 or more study visits (20% lasting 12-18 months, but very low n)

 

so, oral HPV infections quite uncommon and mostly cleared within one year (as with vaginal infections in women). reinforces widespread use of vaccine. there was one study in costa rica, reported in PLOS One, which did find a decrease in oral HPV in women who were vaccinated. i do not know of any studies in men. but makes sense to immunize men and women, as recommended by CDC.

 

geoff

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