Age when to vaccinate against HPV ?

  At what age girls/ women should have HPV vaccination? What is the Cost-effectiveness of vaccinating multiple age cohorts? Options are 9-14 yrs/ at 18 yrs/ at 24 yrs age / at 26 yrs of age / Universal at 12 years as National Policy

Most studies reported that immunization targeting multiple age cohorts were cost-effective due to wider primary protection and more rapid herd effects. Specifically, the multiple age-cohort female vaccination strategy was cost-effective in the age range of 9-14 years old. However, the cut-off range where HPV vaccination was no longer cost-effective varied among studies and was more important in differentiating between studies than their overall conclusions. Nine studies concluded that HPV vaccination was cost-effective until the age of 24, three studies up to the age of 25 and one study till the age of 26.
However, it is important to address that two of these cost¬effectiveness studies compared multiple age-cohort vaccination to no vaccination strategy instead of routine vaccination of female aged 12. However, the extension of immunization age needs to be interpreted cautiously as several studies analysed the cost-effectiveness of HPV immunization in a single age range only and did not compare in the next age range gradually. When HPV vaccination was compared in the next age range gradually, it was cost-effective till the age of 18 years only in two studies and 15 years in one study. However, above the age of 15 years, the upper age limit at which HPV immunization stop being cost-effective depends on the country context. A study in United Kingdom concluded that HPV vaccination up to the age of 18 years was only cost-effective in the presence of protection to non-naive women, demonstrating that the exclusion of vaccine protection among non-naive women may underestimate the cost-effectiveness of vaccinating additional older age women. A Canadian study found that HPV vaccination till the age of 18 years was cost-effective irrespective of the delivery method, with school-based delivery had a lower ICER compared to clinic-based delivery. Among the seventeen studies, only one study reported that multiple age-cohort vaccination (17-25 years) was not cost-effective unless vaccine price in Netherlands was reduced by 52%.Duration of vaccine protection and vaccine price influences the cost-effectiveness of targeting multiple age-cohort immunization. If duration of vaccine protection is reduced to a minimum of 10 years, the cost-effectiveness ratio increases and is only cost-effective in the broader age range of immunization, 12-24 years old. Hence, further economic evidences on immunization based on multiple age cohorts are still required especially in LMIC and also in determining the most cost-effective age limit of HPV vaccinaation.

Do we know that  many  oropharyngeal cancers are attributable to HPV. However etiology  varies greatly being highest in more developed countries (up to 70% in the most recent studies in the USA and some North European countries) due to HPV , but much lower (<20%) and still uncertain in many countries. For cancers of the oral cavity (4,900 cases per year attributed to HPV of whom 3,200 men) and larynx (3,800, of whom 3,200 men), the prevalence of HPV was evaluated only in a few case series. Most of the studies were conducted in Europe and North America, and yielded an average prevalence of approximately 4% at both sites.

HPV AF in cancers of the oral cavity and larynx is lower (1-2%) in the rest of the world in which

tobacco smoking and chewing are still very common. On account of a greater predominance of HPV16 compared to cervical cancer, HPV 16 and 18 are globally responsible for 85% of cancer of the head and neck while the relative contribution of HPV 6/11/16/18/31/33/45/52/58 is 90% (Table 6).

The role of following subtypes of HPV like

Types 6/11/16/18/31/33/45/ 52/58 types is 73% and 90%,   . AF  (attributable fraction) for HPV is relatively accurate compared to AF for other infectious agents and, by and large, for lifestyle factors on account of the predominant weight of cervical cancer for which HPV is considered a necessary cause. Substantial limitations of the AFs(, attributable fraction.) presented in this report include, however, lack of HPV prevalence data and accurate cancer incidence rates for many countries. In addition, an accurate classification of the site/subsite of cancer origin in the head and neck and the anogenital tract (other than the cervix) is difficult when cancer diagnosis is made in advanced stages and hence the burden of these disease is likely to be underestimated in less developed regions. The relative contribution of the nine HPV types in cervical cancer and other anogenital cancers may be overestimated because of the high frequency of multiple infections especially if newer very sensitive HPV assays are used.

Conclusions. Overall, 640,000 cancer cases are attributable to HPV every year. Wide geographical variation in the fraction of cancers attributable to HPV exists by region, sex, and age group. HPV- attributable cancers account for 8.6% and 0.8% of all cancers in women and men, respectively. HPV AF of all cancers in women ranges from <3% in Australia/New Zealand and the US to 26% in Sub­Saharan Africa. Globally, the relative contribution of HPV 16/18 and of HPV 6/11/16/18/31/33/45/ 52/58 types is 73% and 90%, respectively .The population AFs (attributable fraction) that are shown in this report represent a useful base for prediction models and a potential incentive to act. However, AF should not be confused with the number of preventable cancers, i.e. fraction of cases that can be prevented by specific intervention(s) in a specific time frame.

What are high-risk or oncogenic types Burden of HPV-attributable cancers by anatomical sites, sex, countries and HPV types??

Ans: HPV alpha types 16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59 as carcinogenic to humans (Group 1), and HPV alpha type 68 as(total 13 types)  probably carcinogenic (Group 2A)..

HPV were repeatedly assessed by the International Agency for Research on Cancer (IARC) Monographs on the Evaluation of Carcinogenic Risks to Humans (Monographs N°64, 90, and 100B). After thoroughly reviewing epidemiological studies and mechanistic studies, the IARC working group classified HPV alpha types 16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59 as carcinogenic to humans (Group 1), and HPV alpha type 68 as probably carcinogenic (Group 2A).

These thirteen types are commonly referred to as high-risk or oncogenic types.

 

Which sites?  Ans: Cancer sites for which the evidence of HPV involvement is considered sufficient are cervix uteri, vulva, vagina, penis, anus, oral cavity, and oropharynx.

The IARC working group also observed that there were positive associations for larynx. Further evidence for larynx has since accumulated and we include it in our list of cancer sites for HPV in our attributable risk estimates.

What about Cervical cancers?? Most cervical cancers result from HPV16/18 types (73%) and HPV6/11/16/18/31/33/45/52/58 types (90%) of infections and therefore are preventable through screening and vaccination. 4.5% of new cancer cases, including cancers of the cervix, anogenital tract and head and neck, are associated with HPV infection.

 

What is the relevance of  HPV screening and vaccination and the need for less-costly vaccines??.

Cervical cancer alone accounts for 83% of those cases, most of which affect women in less-developed countries. The findings emphasize the importance of HPV screening and vaccination and the need for less-costly vaccines.