HPV Vaccination in Québec: Knowledge Update and Expert Panel Proposals
The human papillomavirus (HPV) belongs to the Papillomaviridae family, which includes at least 100 genotypes affecting the skin and mucous membranes. Of these, about 40 affect the anogenital area in particular, and approximately 15 are oncogenic. Genotypes 16 and 18 are responsible for 70-76% of cervical cancer cases worldwide. Genotypes 6 and 11 are non-oncogenic but are responsible for most cases of condyloma (anogenital warts [AGW]).
HPV prevalence and incidence data are estimated on the basis of epidemiological studies and are better documented in women than men. HPV prevalence varies widely by geographic region, age, the selected subpopulation and HPV detection method. In women, the overall age-adjusted prevalence of genital infections worldwide is estimated at 11.7%. It peaks in young women aged 20-24 and declines subsequently with age. The risk of acquiring HPV infection is particularly high in the first few years after sexual activity begins. According to some estimates, more than 70% of sexually active women will contract an HPV infection at some time in their lives. Among men, the prevalence of genital infection is just as high, if not higher, but varies less with age.
HPV is usually transmitted sexually, and the risk of contracting the infection is largely determined by sexual behaviour, including the number of sexual partners. While the infection is common in the population, the majority of infections will clear spontaneously. A persistent infection increases the risk of progression to cancer, but this process takes many years, which explains why cervical cancer is rare before the age of 30 and practically non-existent before the age of 20. The precursor stages of cervical cancer can be detected by cytological screening (Pap test), and there are effective treatments for halting the progression to cancer. However, over half of cervical cancer cases are currently associated with inadequate screening.
A number of cancers are caused by HPV. In Québec, from 2004 to 2007, there were an average of 281 new cervical cancer cases and 69 deaths per year. HPV is also associated with a certain proportion of cancers of the anogenital area, including cancers of the anus (83%), vulva (66%), vagina (70%) and penis (49%). It is also found in cases of oropharyngeal cancer (47%) and, to a lesser extent, in cancers of the oral cavity (16%) and larynx (14%). HPV 16 is the genotype most frequently associated with these types of cancer.
When the proportion of cancers attributable to HPV and especially to genotypes 16 and 18 (as estimated from the data in the literature) is applied to those cancers associated with HPV1 that were reported during the 2004-2007 period, the number of potentially vaccine-preventable cancer cases is 356 per year in women and 179 in men. Excluding cancers of the oral cavity and larynx (whose causal link with HPV infection is still under study), the number of potentially preventable cancers is 339 in women and 129 in men.
In estimating this clinical burden, one must also include the substantial resources allocated to cervical cancer screening. Over 1 million cervical cancer screening tests are performed every year in Québec, not to mention the resources devoted to the assessment of abnormal results and the treatment of precursor stages.
The non-oncogenic HPV types also contribute to the burden of disease. AGW, usually associated with genotypes 6 and 11, affect both men and women with peak incidence observed before the age of 30. In Canada, only Manitoba and British Columbia currently have population-based data on the incidence and prevalence of this disease, estimated from the number of medical visits for the condition. In Manitoba, women aged 20-24 (5.7/1,000 person-years) and men aged 25-29 (4.6/1,000 person-years) had the highest rates. In British Columbia, between 1998 and 2006 the standardized incidence rate was 1.3/1,000 person-years among men and 1.2/1,000 person-years among women. Applying these data to the Québec population yields an estimated 14,000 cases of AGW diagnosed annually in Québec men and women.
Recurrent respiratory papillomatosis (RRP), which is also associated with genotypes 6 and 11, can affect both adults and young children. In Canada, the incidence of the juvenile form is estimated at 0.24 per 100,000 child-years among children under the age of 14 (there are approximately two new cases per year in Québec). While rare, the disease can lead to a high level of morbidity and repeated surgery in some individuals.
The two HPV vaccines approved for use in Canada have proven to be immunogenic in the short and medium term. Both vaccines are more immunogenic and better tolerated when administered in preadolescence and adolescence. Two doses of the bivalent or quadrivalent vaccine administered at 6-month intervals to individuals aged 9-14 induce antibody titres similar to or higher than those observed after three doses of vaccine administered to individuals aged 15-26 in whom clinical efficacy has been demonstrated. There are no important differences in vaccine immunogenicity between males and females of the same age. Most of the data from clinical studies conducted by the vaccine manufacturers are difficult to compare. Only one study directly compares the immunogenicity of the two vaccines, and it shows that the bivalent vaccine is more immunogenic for HPV 16, HPV 18 and certain other HPV types (HPV 31, HPV 33, HPV 45) closely related genetically to the two included in both vaccines. However, the quadrivalent vaccine induces additional immunity against HPV 6 and HPV 11, which are responsible for non-cancerous lesions associated with HPV (primarily AGW and RRP).
Vaccine efficacy data are limited to individuals aged 15 and over. In women, both vaccines have proven efficacious in preventing:
- cervical, vulvar and vaginal cancers and their precursors caused by HPV 16 and HPV 18, and
- cervical adenocarcinoma in situ.
In both males and females the quadrivalent vaccine is also efficacious in preventing AGW caused by HPV types 6 and 11 as well as anal cancers and their precursors caused by HPV 16 and HPV 18.
Approval of the vaccines for individuals under the age of 15 has been based exclusively on bridging immunogenicity studies.
Vaccine efficacy appears to decline with age at administration. There are two possible explanations for the decline in efficacy with age: 1) a weaker immune response and 2) a higher percentage of individuals who are infected before receiving the vaccine.
The duration of clinical vaccine efficacy as currently known is at least nine years in females and at least three years in males.
There are no head-to-head comparisons of the efficacy of the two vaccines. The study eligibility criteria, the point at which infections and lesions are counted, and the way in which the results are analyzed and presented are different for the two vaccines. In the medium term, some fairly similar cohort analyses show excellent efficacy of both vaccines against persistent infections and lesions due to the HPV types included in the vaccine. Both vaccines have also shown some degree of cross-protection. The existing data seem to show greater cross-protection after administration of the bivalent vaccine. The duration of protection against the vaccine HPV types and the duration of cross-protection are still unknown.
The population-level impact of immunization two to four years after implementation of a program with the quadrivalent vaccine has been reported for AGW. Ecological data from some sexually transmitted disease clinics in Australia show a decrease of up to 90% in the percentage of individuals with a diagnosis of AGW. While it is difficult to extrapolate these data to the general population, they do indicate the possibility that implementing a vaccination program with the quadrivalent vaccine will result in a considerable decrease in AGW within a relatively short period of time.
There have been relatively few studies on the efficacy of a reduced number of doses. However, the limited available data on the immunogenicity and efficacy of schedules that include only two doses are encouraging.
The efficacy of both HPV vaccines in reducing the number of cytological abnormalities and subsequent procedures has also been demonstrated and ranges from 20% to 33%.
It is plausible that both HPV vaccines protect against certain non-anogenital cancers associated with HPV 16 and HPV 18 and that the quadrivalent vaccine protects against RRP as well. However, there are currently no clinical data on the impact of vaccination on these diseases.
On the basis of the existing data, the two HPV vaccines approved for use in Canada are efficacious in the short and medium term, and both could be used in the publicly funded vaccination program. However, only the quadrivalent vaccine protects against AGW.
Both vaccines are well tolerated. Mild and moderate injection site reactions are apparently more frequent following administration of the bivalent vaccine. There is no increase in adverse reactions with the number of vaccine doses administered.
Acceptability, feasibility and ethical issues
Recent data show that the majority of both the general public and health care professionals favour the vaccination of girls aged 9-17. They also approve of vaccinating boys, as well as women aged 18-26. The cost of the vaccine is the greatest barrier, and a physician's recommendation is the most decisive factor in the acceptability of vaccination.
In Québec, in 2010-2011, HPV vaccine coverage rates in elementary grade 4 and Secondary III (grade 9) exceeded 75%, indicating high acceptability of vaccination among parents for their daughters and among teenaged girls.
The results of the survey of Québec health care professionals, while requiring cautious interpretation because of the low response rate, indicate significant interest in the vaccination of boys, although women aged 18-26 were selected as the first priority if the publicly funded vaccination program were expanded.
Organizing the delivery of vaccination services is a major challenge for any vaccination program aimed at women in the 18-26 age group, who generally cannot be reached through school-based programs. However, the vaccination of school-aged boys appears to be easier to achieve. Indeed, expanding HPV vaccination to the entire school population rather than targeting just girls could be done fairly easily. In both cases, it would be essential to devote more effort to informing and educating the public and health care professionals about the important role of vaccines in preventing diseases caused by HPV, and it can be assumed that vaccine coverage in boys would be comparable to that in girls.
Several ethical issues have already been raised in connection with HPV vaccination. More issues will arise with approval of the bivalent vaccine for girls and women aged 10-25 and of the quadrivalent vaccine both for women over the age of 26 and for boys and young men aged 9-26.
First, the lack of a publicly funded HPV vaccination program aimed at women over the age of 18 and at young men raises ethical issues of social justice. As well, there are risks of stigmatization if, for epidemiological or logistical reasons, HPV vaccines were offered free of charge only to certain subgroups of the population (men who have sex with men [MSM] and HIV-positive individuals). Lastly, choosing the objective of the publicly funded vaccination program could raise the issue of whether it adheres to the principle of utility (cost/benefit).
School vaccination for girls with the bivalent or quadrivalent vaccine is highly cost-effective, and the cost-effectiveness ratio of the quadrivalent vaccine continues to be lower than that of the bivalent vaccine in almost all the scenarios that have been analyzed, assuming that vaccine costs are equal.
In all the scenarios analyzed, the cost-effectiveness ratio of vaccinating only girls with the bivalent or quadrivalent vaccine is below the generally accepted Québec cost-effectiveness threshold. The existing vaccination program for girls is therefore considered cost-effective. In almost all these scenarios, the estimated cost-effectiveness ratio for the bivalent vaccine is higher than for the quadrivalent vaccine, assuming that vaccine costs are equal. The difference is mainly attributable to the burden of AGW prevented with the quadrivalent vaccine. The bivalent vaccine would therefore have to cost less than the quadrivalent vaccine in order for it to represent an economically worthwhile alternative to the quadrivalent vaccine.
Adding the vaccination of boys to the existing vaccination program for girls would likely not be cost-effective and would provide very few additional benefits to women and heterosexual men; most of the benefits would go to MSM.
The analyses predict that in heterosexual men, there will be a significant reduction in the burden related to diseases caused by HPV through the indirect protection (herd immunity) conferred on them by the vaccination of girls with the quadrivalent vaccine. Most of the benefits of the vaccination of boys would go to MSM, who presumably are unprotected by the vaccination of girls but who represent a small percentage of the male population. For all the scenarios considered, the economic analyses predict that adding the vaccination of boys to that of girls would result in cost-effectiveness ratios far higher than the generally accepted Québec threshold.
The objective that most of the participants in the Ad Hoc Scientific Committee agreed on is the following:
Reduce the incidence, morbidity and mortality of cancers, precancerous lesions and other diseases associated with HPV.
The Committee believes that the available information on the immunogenicity and clinical efficacy of the quadrivalent HPV vaccine and the preliminary results of Phase IV studies in other countries demonstrate that the Québec program, consisting of routine vaccination of girls in grade 4 and a catch-up program up to the age of 18 with a quadrivalent vaccine, will be effective in reducing the burden of precancerous lesions and cancers attributable to HPV, as well as AGW, in the target population. The vaccine coverage currently achieved (± 80%) in girls is also expected to have a considerable indirect impact on the male heterosexual population, with respect to both AGW and certain cancers. Modelling results also indicate that the program will be cost-effective (< $20,000/quality-adjusted life-year [QALY]) on the basis of the standards generally accepted in Québec.
Replacing the quadrivalent vaccine (Gardasil®) with the bivalent vaccine (CervarixTM) would mean abandoning the goal of preventing diseases caused by HPV types 6 and 11, such as AGW and potentially laryngeal papillomatosis. However, the prevention of cancers would be slightly improved should the bivalent vaccine confer greater cross-protection against certain oncogenic types. Economic analyses conducted in Québec show that to be as cost-effective as the quadrivalent vaccine, the bivalent vaccine would have to cost considerably less. The majority of the members of the Ad Hoc Scientific Committee expressed reservations about the possibility of abandoning protection against AGW (both in girls through direct protection and in boys through herd immunity). Abandoning such protection could also trigger negative reactions from health care professionals and the public. On the other hand, replacing the quadrivalent vaccine with the bivalent vaccine could minimize program costs should the bivalent vaccine prove to cost significantly less than the quadrivalent vaccine.
The efficacy of the quadrivalent vaccine in men has been well demonstrated. However, adding universal vaccination of preadolescents would have only a marginal impact on the male heterosexual population, as long as vaccine coverage in the female population is maintained. The major benefit of a free vaccination program for boys would be to reduce the burden of AGW and certain cancers in men who will later have sexual relations with men, because they will have been vaccinated at the time when vaccine efficacy is highest (i.e. Before the start of sexual relations). However, at the current cost of the quadrivalent vaccine, extending the program to all preadolescent boys in order to provide more protection to a minority of them would not be cost-effective (> $180,000/QALY) according to generally accepted standards. A free vaccination program for all boys could be justified by political and equity considerations, primarily with respect to MSM, but not by arguments of significant epidemiological impact or efficiency of the program. In the event of a substantial reduction in the cost of the quadrivalent vaccine, such conclusions could change.
Extending the existing program in order to provide free vaccination to women aged 18 and over would probably have a limited impact on the burden of diseases caused by HPV in this population. The magnitude of the reduction is difficult to determine for each age group. Vaccine efficacy declines when vaccination takes place after the start of sexual activity. Approximately 50% of women aged 18-20 are already vaccinated, since they have been targeted by the catch-up program since 2008. Extending the existing program would be quite expensive, because three doses of the vaccine would have to be administered outside the school environment. The cost-effectiveness ratios of such an extension would definitely be less favourable than those achieved by the existing school-based program aimed at girls under the age of 18. There is also considerable uncertainty about the feasibility of such an addition to the program and the level of vaccine uptake that could be achieved.
The implementation of pilot projects for targeted vaccination of MSM could be explored, since free vaccination of all preadolescents is not an efficient strategy with the current cost of the vaccines. The scientific evidence suggests that the effectiveness of such a strategy, whereby the vaccine would in most cases be administered after the start of sexual relations, may be limited. Furthermore, the feasibility, acceptability and cost of such a program have not been carefully evaluated. Studies would have to be conducted to examine these aspects.
The vaccination of certain other population subgroups deemed at greater risk of acquiring HPV-associated diseases (e.g. Aboriginal people) or of experiencing complications (e.g. people with certain chronic diseases) could also be explored. A careful and specific analysis of this issue, which was not possible within the framework of this advisory report, should be understaken.
HPV: Uhakikisho wa Ujuzi na Mapendekezo ya Jopo la Wataalamu Virusi vya Papillomavirus ya Binadamu (HPV) ni sehemu ya familia ya Papillomaviridae, ambayo inajumuisha angalau genotypes 100 zinazoathiri ngozi na utando wa utando. Kati ya hizo, 40 huathiri eneo la anogenital, na 15 ni oncogenic. Genotypes 16 na 18 ni wajibu kwa asilimia 70 hadi 76 ya maambukizi ya saratani ya shingo ya tumbo la uzazi duniani kote. Genotypes 6 na 11 ni non-oncogenic lakini ni wajibu kwa ajili ya kesi nyingi za condyloma (anogenital warts [AGW]). Takwimu za kuenea na maambukizi ya HPV zinakadiriwa kwa msingi wa masomo ya magonjwa ya kuambukiza na zimeandikwa vizuri zaidi kwa wanawake kuliko wanaume. Ugonjwa wa HPV unatofautiana sana kulingana na eneo la kijiografia, umri, idadi ya watu waliochaguliwa na njia ya kugundua HPV. Katika wanawake, jumla ya umri-kurekebishwa kuenea kwa maambukizi ya viungo vya uzazi duniani kote ni takriban 11.7%. Kiwango cha juu ni kwa wanawake vijana wenye umri wa miaka 20-24 na hupungua baadaye na umri. Hatari ya kuambukizwa HPV ni kubwa hasa katika miaka michache ya kwanza baada ya kuanza kufanya ngono. Kulingana na takwimu, zaidi ya asilimia 70 ya wanawake wanaofanya ngono watapata maambukizi ya HPV wakati fulani katika maisha yao. Katika wanaume, kuenea kwa maambukizo ya viungo vya uzazi ni ya juu kama vile, kama si ya juu, lakini inatofautiana kidogo na umri. HPV ni kawaida kuambukizwa kwa njia ya ngono, na hatari ya kuambukizwa ni hasa kuamua na tabia ya ngono, ikiwa ni pamoja na idadi ya washirika wa ngono. Ingawa maambukizo ni ya kawaida katika idadi ya watu, idadi kubwa ya maambukizo itaondolewa kwa hiari. Ugonjwa wa utumbo unaendelea na kuendeleza hatari ya kuenea kwa saratani, lakini mchakato huu huchukua miaka mingi, ambayo inaelezea kwa nini saratani ya shingo ya tumbo ni nadra kabla ya umri wa miaka 30 na karibu haipo kabla ya umri wa miaka 20. Hatua za mwanzo za saratani ya shingo ya tumbo la uzazi zinaweza kugunduliwa kwa uchunguzi wa cytological (mtihani wa Pap), na kuna matibabu yenye ufanisi ya kuzuia maendeleo ya saratani. Hata hivyo, zaidi ya nusu ya visa vya kansa ya shingo ya tumbo la uzazi kwa sasa vinahusishwa na uchunguzi usiofaa. Aina kadhaa za kansa husababishwa na HPV. Katika kipindi cha mwaka 2004 hadi 2007, nchini Quebec, kulikuwa na wastani wa visa vipya 281 vya saratani ya shingo ya tumbo la uzazi na vifo 69 kwa mwaka. Ugonjwa huo pia unahusishwa na asilimia fulani ya saratani za eneo la anogenital, ikiwa ni pamoja na saratani za anus (83%), vulva (66%), vagina (70%) na penis (49%). Ugonjwa huo pia unapatikana katika saratani ya mdomo na pua (47%) na, kwa kiwango kidogo, katika saratani ya mdomo (16%) na larynx (14%). HPV16 ni aina ya genotype inayohusishwa zaidi na aina hizi za kansa. "Kama uwiano wa saratani zinazohusiana na HPV na hasa genotypes 16 na 18 (kama inakadiriwa kutoka kwa data katika fasihi) inatumika kwa saratani zinazohusiana na HPV1 ambazo ziliripotiwa wakati wa kipindi cha 2004-2007, idadi ya uwezekano wa kuzuia chanjo ya saratani ni 356 kwa mwaka kwa wanawake na 179 kwa wanaume.""" Ikiwa ni pamoja na saratani ya mdomo na larynx (ambayo uhusiano wa sababu na maambukizo ya HPV bado unachunguzwa), idadi ya saratani zinazoweza kuepukwa ni 339 kwa wanawake na 129 kwa wanaume. Katika kukadiria mzigo huu wa kliniki, mtu lazima pia kujumuisha rasilimali kubwa iliyotengwa kwa uchunguzi wa saratani ya shingo ya tumbo la uzazi. Zaidi ya milioni moja ya uchunguzi wa saratani ya shingo ya tumbo la uzazi hufanywa kila mwaka katika Quebec, bila kutaja rasilimali zilizotumika kwa tathmini ya matokeo ya kawaida na matibabu ya hatua za awali. Aina za HPV zisizo za oncogenic pia huchangia mzigo wa ugonjwa. AGW, ambayo kwa kawaida inahusishwa na genotypes 6 na 11, huathiri wanaume na wanawake na kiwango cha juu cha maambukizi huonekana kabla ya umri wa miaka 30. Manitoba na British Columbia tu nchini Canada zina takwimu za idadi ya watu kuhusu ugonjwa huu, kulingana na idadi ya ziara za daktari. Katika Manitoba, wanawake wenye umri wa miaka 20-24 (5,7%) na wanaume wenye umri wa miaka 25-29 (4,1%) walikuwa na viwango vya juu zaidi. Katika miaka ya 1998 hadi 2006, kiwango cha kawaida cha maambukizi kilikuwa 1.33 kwa watu 1,000 kwa mwaka kwa wanaume na 1.2 kwa watu 1,000 kwa mwaka kwa wanawake. Kwa kutumia takwimu hizi kwa idadi ya watu wa Quebec, inatoa takriban visa 14,000 vya AGW vilivyogunduliwa kila mwaka katika wanaume na wanawake wa Quebec. Papillomatosis ya kupumua (RRP) ni ugonjwa wa kawaida wa watoto na watu wazima. Katika Canada, kiwango cha ugonjwa wa watoto ni 0.24 kwa kila miaka 100,000 ya watoto chini ya miaka 14 (kuna karibu kesi mbili mpya kwa mwaka katika Quebec). Ingawa ugonjwa huo ni nadra, unaweza kusababisha ugonjwa mwingi na upasuaji mara kwa mara kwa watu fulani. Chanjo mbili za HPV zilizoidhinishwa kwa matumizi nchini Canada zimethibitika kuwa immunogenic kwa muda mfupi na wa kati. Chanjo zote mbili ni immunogenic zaidi na kuvumiliwa vizuri wakati kutumika katika preadolescence na ujana. Dawa mbili za chanjo ya bivalent au quadrivalent, zinazotumiwa kwa vipindi vya miezi sita kwa watu wenye umri wa miaka 9-14 huchochea titers za kingamwili sawa na au juu kuliko zile zilizochunguzwa baada ya dozi tatu za chanjo zilizotumiwa kwa watu wenye umri wa miaka 15-26 ambao ufanisi wa kliniki umeonyeshwa. Hakuna tofauti muhimu katika immunogenicity chanjo kati ya wanaume na wanawake wa umri huo huo. Takwimu nyingi kutoka kwa masomo ya kliniki yaliyofanywa na watengenezaji wa chanjo ni ngumu kulinganisha. Utafiti mmoja tu unafananisha moja kwa moja immunogenicity ya chanjo mbili, na inaonyesha kwamba chanjo ya bivalent ni immunogenic zaidi kwa HPV 16, HPV 18 na aina zingine za HPV (HPV 31, HPV 33, HPV 45) zinazohusiana sana na aina mbili zilizowekwa katika chanjo zote mbili. Kwa mujibu wa utafiti, chanjo ya quadrivalent ya HPV-1 inatoa kinga ya ziada dhidi ya HPV-11, ambayo ni wajibu kwa ajili ya lesions noncancerous kuhusishwa na HPV (hasa AGW na RRP). Takwimu za ufanisi wa chanjo zinahusu watu wenye umri wa miaka 15 na zaidi. Katika wanawake, chanjo zote mbili zimeonekana kuwa na ufanisi katika kuzuia: saratani ya shingo ya tumbo la uzazi, vulva na ya mkojo na watangulizi wao inayosababishwa na HPV 16 na HPV 18 na adenocarcinoma ya shingo ya tumbo la uzazi in situ. Kwa wanaume na wanawake, chanjo ya quadrivalent pia ina ufanisi katika kuzuia AGW inayosababishwa na HPV aina 6 na 11, pamoja na saratani ya mkojo na watangulizi wao inayosababishwa na HPV 16 na HPV 18. "Ukubali wa chanjo kwa watu walio chini ya umri wa miaka 15 umejengwa tu juu ya masomo ya ""kuunganisha"" immunogenicity." Inaonekana kwamba ufanisi wa chanjo hupungua kadiri mtu anavyozeeka. Kuna maelezo mawili ya uwezekano kwa kupungua kwa ufanisi na umri: 1) majibu dhaifu ya kinga na 2) asilimia kubwa ya watu ambao wameambukizwa kabla ya kupokea chanjo. Ufanisi wa chanjo ya kliniki unajulikana kwa sasa ni angalau miaka tisa kwa wanawake na angalau miaka mitatu kwa wanaume. Hakuna kulinganisha moja kwa moja kwa ufanisi wa chanjo hizo mbili. Vigezo vya kuhitimu kwa ajili ya utafiti, wakati ambapo maambukizo na majeraha yanahesabiwa, na jinsi matokeo yanavyochambuliwa na kuwasilishwa ni tofauti kwa chanjo hizo mbili. Katika muda wa kati, baadhi ya uchambuzi wa kundi sawa unaonyesha ufanisi mzuri wa chanjo zote mbili dhidi ya maambukizo ya kudumu na majeraha kutokana na aina za HPV zilizojumuishwa katika chanjo. Chanjo zote mbili pia zimeonyesha kiwango fulani cha ulinzi wa msalaba. Takwimu zilizopo zinaonekana kuonyesha ulinzi mkubwa zaidi baada ya utoaji wa chanjo ya bivalent. Muda wa ulinzi dhidi ya aina za HPV za chanjo na muda wa ulinzi wa msalaba bado haujulikani. Matokeo ya chanjo ya watu wote miaka miwili hadi minne baada ya utekelezaji wa mpango wa chanjo ya quadrivalent yameripotiwa kwa AGW. Takwimu za kiikolojia kutoka kwa kliniki za magonjwa ya kuambukizwa kingono nchini Australia zinaonyesha kupungua kwa asilimia 90 ya watu walio na ugonjwa wa AGW. Ingawa ni vigumu kupanua data hizi kwa idadi ya watu kwa ujumla, zinaonyesha uwezekano kwamba kutekeleza mpango wa chanjo na chanjo ya quadrivalent itasababisha kupungua kwa kiasi kikubwa katika AGW ndani ya kipindi kifupi cha muda. Kumekuwa na masomo machache sana juu ya ufanisi wa idadi ndogo ya dozi. Hata hivyo, data ndogo zinazopatikana juu ya immunogenicity na ufanisi wa ratiba ambazo ni pamoja na dozi mbili tu ni kuhamasisha. Ufanisi wa chanjo zote mbili za HPV katika kupunguza idadi ya kasoro za cytological na taratibu za baadaye pia zimeonyeshwa na huanzia 20% hadi 33%. Kwa hivyo, ni uwezekano kwamba chanjo zote mbili za HPV zinalinda dhidi ya saratani fulani zisizo za anogenital zinazohusiana na HPV 16 na HPV 18 na kwamba chanjo ya quadrivalent inalinda dhidi ya RRP pia. Hata hivyo, kwa sasa hakuna data ya kliniki juu ya athari ya chanjo juu ya magonjwa haya. Kwa mujibu wa data zilizopo, chanjo mbili za HPV zilizokubaliwa kwa matumizi nchini Canada zina ufanisi katika muda mfupi na wa kati, na zote mbili zinaweza kutumika katika mpango wa chanjo unaofadhiliwa na umma. Hata hivyo, chanjo ya quadrivalent tu inalinda dhidi ya AGW. Chanjo zote mbili zinasamehewa vizuri. Madhara ya kiasi na ya wastani katika eneo la sindano ni ya kawaida zaidi baada ya utoaji wa chanjo ya bivalent. Hakuna ongezeko la athari mbaya na idadi ya dozi za chanjo zilizotumiwa. Uwezekano wa chanjo ya watoto wa kike wa umri wa miaka 9-17: Takwimu za hivi karibuni zinaonyesha kwamba idadi kubwa ya watu na wataalamu wa huduma za afya wanapendelea chanjo ya wasichana wa umri wa miaka 9-17. Pia, inapaswa kupewa chanjo kwa wavulana na wanawake wenye umri wa miaka 18 hadi 26. Gharama ya chanjo ni kikwazo kikubwa, na mapendekezo ya daktari ni sababu muhimu zaidi katika kukubalika kwa chanjo. Katika mwaka wa 2010, kiwango cha chanjo ya HPV katika shule za msingi na sekondari kilizidi asilimia 75 na inaonyesha kuwa wazazi wa watoto wao na wasichana vijana wanafurahia chanjo. Matokeo ya utafiti wa wataalamu wa huduma za afya wa Quebec, ingawa yanahitaji tafsiri ya tahadhari kwa sababu ya kiwango cha chini cha majibu, yanaonyesha nia kubwa katika chanjo ya wavulana, ingawa wanawake wenye umri wa miaka 18-26 walichaguliwa kama kipaumbele cha kwanza ikiwa mpango wa chanjo unaofadhiliwa na umma ungepanuliwa. """Kupanga utoaji wa huduma za chanjo ni changamoto kubwa kwa programu yoyote ya chanjo inayolenga wanawake katika kikundi cha umri wa miaka 18-26 ambao kwa ujumla hawawezi kufikiwa kupitia programu za shule." Hata hivyo, inaonekana ni rahisi zaidi kuwa chanjo ya wavulana wenye umri wa kwenda shuleni. Kwa kweli, kupanua chanjo ya HPV kwa idadi nzima ya shule badala ya kulenga wasichana tu inaweza kufanywa kwa urahisi. Katika hali zote mbili, ni muhimu kujitolea zaidi kwa kuelimisha na kuelimisha umma na wataalamu wa huduma za afya juu ya jukumu muhimu la chanjo katika kuzuia magonjwa yanayosababishwa na HPV, na inaweza kudhaniwa kuwa chanjo ya chanjo kwa wavulana itakuwa sawa na ile kwa wasichana. Masuala kadhaa ya maadili tayari yameulizwa kuhusiana na chanjo ya HPV. "Mashtaka hayo yanajumuisha ""kutoa chanjo ya bivalent kwa wasichana na wanawake wenye umri wa miaka 10-25 na chanjo ya quadrivalent kwa wanawake wenye umri wa miaka 26 na zaidi na kwa wavulana na vijana wenye umri wa miaka 9-26.""" Kwa upande mwingine, ukosefu wa mpango wa chanjo ya HPV unaofadhiliwa na umma kwa wanawake wenye umri wa miaka 18 na vijana wa kiume unaibua masuala ya maadili ya haki ya kijamii. Pia, kuna hatari ya utambuzi ikiwa, kwa sababu za magonjwa ya kuambukiza au za vifaa, chanjo za HPV zilitolewa bila malipo tu kwa vikundi fulani vya watu (wanaume wanaofanya ngono na wanaume [MSM] na watu walio na virusi vya Ukimwi). Mwishowe, kuchagua lengo la mpango wa chanjo unaofadhiliwa na umma inaweza kuibua suala la ikiwa inashikamana na kanuni ya manufaa (gharama-faida). """Mchango wa chanjo ya shule kwa wasichana na chanjo ya bivalent au quadrivalent ni ufanisi sana wa gharama, na uwiano wa ufanisi wa gharama ya chanjo ya quadrivalent inaendelea kuwa chini kuliko ile ya chanjo ya bivalent katika karibu matukio yote ambayo yamechunguzwa, kwa kudhani kuwa gharama za chanjo ni sawa." Katika matukio yote kuchambuliwa, uwiano wa gharama-ufanisi wa chanjo tu wasichana na chanjo bivalent au quadrivalent ni chini ya Quebec kawaida kukubaliwa gharama-ufanisi kizingiti. Kwa hiyo, programu ya sasa ya chanjo ya wasichana inachukuliwa kuwa yenye matokeo kwa gharama. Katika hali zote, uwiano wa gharama za ufanisi wa chanjo ya bivalent ni kubwa kuliko chanjo ya quadrivalent, ikidhani kuwa gharama za chanjo ni sawa. Tofauti hiyo inatokana hasa na mzigo wa AGW iliyoepukwa na chanjo ya quadrivalent. Kwa hivyo, chanjo ya bivalent inapaswa kuwa na gharama ya chini kuliko chanjo ya quadrivalent ili kuwakilisha mbadala wa kiuchumi wa chanjo ya quadrivalent. Kuongeza chanjo ya wavulana kwenye mpango wa chanjo ya sasa kwa wasichana kwa uwezekano haingekuwa na ufanisi wa gharama na itatoa faida chache sana kwa wanawake na wanaume wa jinsia tofauti; faida nyingi zingeenda kwa MSM. Uchunguzi huo unakadiria kuwa kwa wanaume wa jinsia tofauti, kutakuwa na kupunguzwa kwa uzito unaohusiana na magonjwa yanayosababishwa na HPV kupitia ulinzi usio wa moja kwa moja (kinga ya kundi) uliopewa na chanjo ya wasichana na chanjo ya quadrivalent. """Mafaa mengi ya chanjo ya wavulana yataenda kwa wanaume wanaofanya ngono na wanaume, ambao kwa kweli hawawezi kulindwa na chanjo ya wasichana, lakini wanawakilisha asilimia ndogo ya idadi ya wanaume." Kwa matukio yote yaliyochukuliwa, uchambuzi wa kiuchumi unatabiri kwamba kuongeza chanjo ya wavulana kwa ile ya wasichana ingesababisha uwiano wa ufanisi wa gharama juu zaidi ya kizingiti cha Quebec kilichokubaliwa kwa ujumla. "Lengo la utafiti huo ni ""kupunguza idadi ya watu wanaopata kansa, majeraha ya kabla ya kansa na magonjwa mengine yanayohusiana na HPV.""" "Kulingana na taarifa zilizopo juu ya immunogenicity na ufanisi wa kliniki wa chanjo ya quadrivalent na matokeo ya awali ya utafiti wa awamu ya nne ya HPV katika nchi nyingine, mpango wa Quebec, unaojumuisha chanjo ya kawaida ya wasichana katika darasa la nne na mpango wa kukamata hadi umri wa miaka 18 na chanjo ya quadrivalent, itakuwa na ufanisi katika kupunguza mzigo wa maambukizi ya precancerous na kansa inayosababishwa na HPV, pamoja na ""AGW.""" Ufikiaji wa chanjo ya sasa (± 80%) kwa wasichana pia unatarajiwa kuwa na athari kubwa ya moja kwa moja kwa idadi ya wanaume wa jinsia tofauti, kwa heshima ya AGW na saratani fulani. Matokeo ya mfano pia yanaonyesha kwamba mpango utakuwa na ufanisi wa gharama (< $ 20,000 kwa mwaka wa maisha uliosawazishwa na ubora [QALY]) kwa msingi wa viwango vya kawaida vilivyokubaliwa huko Quebec. "Kubadilisha chanjo ya quadrivalent (Gardasil) na chanjo ya bivalent (Cervarix) inamaanisha kuacha lengo la kuzuia magonjwa yanayosababishwa na HPV aina 6 na 11, kama vile ""AGW"" na uwezekano wa papillomatosis ya larynx." Hata hivyo, kuzuia kansa ingeweza kuboreshwa kidogo ikiwa chanjo ya bivalent ingetoa ulinzi mkubwa zaidi dhidi ya aina fulani za kansa. Uchambuzi wa kiuchumi uliofanywa huko Quebec unaonyesha kwamba ili kuwa na ufanisi wa gharama kama chanjo ya quadrivalent, chanjo ya bivalent ingekuwa na gharama ndogo sana. "Wanachama wengi wa Kamati ya Sayansi ya Hifadhi ya Wanyama walielezea wasiwasi juu ya uwezekano wa kuacha ulinzi dhidi ya ""Wanyama wa Wanyama wa Wanyama"" (kwa wasichana kupitia ulinzi wa moja kwa moja na kwa wavulana kupitia kinga ya kundi)." Kuacha ulinzi huo kwaweza pia kusababisha itikio baya kutoka kwa wataalamu wa huduma za afya na umma. Kwa upande mwingine, kubadilisha chanjo ya quadrivalent na chanjo ya bivalent inaweza kupunguza gharama za programu ikiwa chanjo ya bivalent itathibitika kuwa na gharama ndogo sana kuliko chanjo ya quadrivalent. Ufanisi wa chanjo ya quadrivalent kwa wanaume umeonyeshwa vizuri. Hata hivyo, kuongeza chanjo ya jumla ya preadolescents itakuwa na athari ndogo tu kwa idadi ya wanaume wa jinsia tofauti, kwa muda mrefu kama chanjo ya chanjo katika idadi ya wanawake inadumishwa. """Faida kubwa ya mpango wa chanjo ya bure kwa wavulana itakuwa kupunguza mzigo wa AGW na saratani fulani kwa wanaume ambao baadaye watakuwa na mahusiano ya kingono na wanaume, kwa sababu watakuwa wamepatiwa chanjo wakati ufanisi wa chanjo ni wa juu zaidi." kabla ya kuanza mahusiano ya kingono. Hata hivyo, kwa gharama ya sasa ya chanjo ya quadrivalent, kupanua mpango kwa wavulana wote wa kabla ya ujana ili kutoa ulinzi zaidi kwa wachache wao haingekuwa gharama nafuu (> $ 180,000 kwa QALY) kulingana na viwango vya kawaida. Programu ya chanjo ya bure kwa wavulana wote inaweza kustahiliwa na kuzingatia kisiasa na usawa, hasa kwa heshima ya MSM, lakini si kwa hoja za athari kubwa ya magonjwa au ufanisi wa programu. Katika tukio la kupunguzwa kwa kiasi kikubwa kwa gharama ya chanjo ya quadrivalent, hitimisho kama hizo zinaweza kubadilika. Kuongeza mpango wa sasa wa chanjo ya bure kwa wanawake wenye umri wa miaka 18 na zaidi kunaweza kuwa na athari ndogo kwa mzigo wa magonjwa yanayosababishwa na HPV katika idadi hii ya watu. Ni vigumu kujua kiasi cha kupungua kwa kila kikundi cha umri. Ufanisi wa chanjo hupungua wakati chanjo inafanyika baada ya kuanza kwa shughuli za kingono. Asilimia 50 ya wanawake wenye umri wa miaka 18 hadi 20 tayari wamepewa chanjo, kwani wamekuwa wakilengwa na mpango wa kukamilisha tangu 2008. Kuongeza muda wa programu hiyo ingekuwa gharama kubwa kwa sababu chanjo tatu zingetolewa nje ya shule. Kwa kweli, uwiano wa gharama na ufanisi wa upanuzi huo utakuwa chini ya zile zilizopatikana na programu ya sasa ya shule inayolenga wasichana chini ya umri wa miaka 18. Kuna pia kutokuwa na uhakika mkubwa kuhusu uwezekano wa kuongeza kama hiyo kwa programu na kiwango cha upatikanaji wa chanjo ambayo inaweza kupatikana. Utekelezaji wa miradi ya majaribio ya chanjo ya lengo la MSM inaweza kuchunguzwa, kwani chanjo ya bure ya watoto wote kabla ya ujana sio mkakati mzuri na gharama ya sasa ya chanjo. "Uhakika wa kisayansi unaonyesha kuwa ufanisi wa mkakati kama huo, ambapo chanjo itawekwa katika kesi nyingi baada ya kuanza mahusiano ya kingono, inaweza kuwa mdogo. """ Isitoshe, uwezekano, kukubalika, na gharama ya programu hiyo hazijachunguzwa kwa uangalifu. Mafunzo yangehitaji kufanywa ili kuchunguza mambo hayo. Kwa hivyo, kuna idadi kubwa ya watu ambao wana hatari kubwa ya kupata magonjwa yanayohusiana na HPV. Aboriginal watu) au ya uzoefu matatizo (kwa mfano Watu wenye magonjwa ya muda mrefu pia wanaweza kugundua. Uchambuzi wa makini na maalum wa suala hili, ambayo haikuwezekana ndani ya mfumo wa ripoti hii ya ushauri, inapaswa kufanywa.