HPV vaccine recommendation update

The Advisory Committee on Immunization Practices of the CDC  just updated their HPV vaccination recommendations to include a 9-valent vaccine (see http://www.cdc.gov/mmwr/preview/mmwrhtml/mm6411a3.htm?s_cid=mm6411a3_e​ ). 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)

--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)